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Coronary Artery Disease Cardiovascular symptoms Calculate pretest probability (likelihood) of CAD Low lntermediate" Highb No additional testing ECG normal and Medical therapy able to exercise? for CAD Yes No ECG abnormal and Exercise ECG able to exercise? . No response to Markedly Yes No therapy positiye test o Lifestyle-limiting symptoms . Progression to Exercise MPl, exercise Pharmacologic MPl, unstable angina echocardiography, or pharmacologic coronary CT angiography echocardiography, or coronary CT angiography

ECG abnormal and Exercise ECG able to exercise? . No response to Markedly Yes No therapy positiye test o Lifestyle-limiting symptoms . Progression to Exercise MPl, exercise Pharmacologic MPl, unstable angina echocardiography, or pharmacologic coronary CT angiography echocardiography, or coronary CT angiography Markedly Markedly positive test positive test Coronary angiography

Markedly Markedly positive test positive test Coronary angiography Stress lest Criteria for Markedly Positive Test Result Exercise ECG Significant ST-segment J at low workload, ST-segment 1, hypotension Exercise/pharmacologic MPI TID or lung intake of thallium, ischemia in >2 vascular distributions, EF <35% Exercise/pharmacologic echocardiography EF <3596 at rest, ischemia in >2 vascular distributions, fall in EF with stress Coronary CT angiography Significant stenosis (>70% in a major epicardial coronary artery) FIGURE 4, Diagnosisof coronaryarterdisease.CAD=coronararterydisease; EF=ejectionfraction; MPI =myocardial perfusionimaging;TlD=transientischemicdilation. 'lntermediate pretesl probabi ity {likelihood) is variably delined as between 1 0% and 90% 0r belween 25"kail75"k.

Stress lest Criteria for Markedly Positive Test Result Exercise ECG Significant ST-segment J at low workload, ST-segment 1, hypotension Exercise/pharmacologic MPI TID or lung intake of thallium, ischemia in >2 vascular distributions, EF <35% Exercise/pharmacologic echocardiography EF <3596 at rest, ischemia in >2 vascular distributions, fall in EF with stress Coronary CT angiography Significant stenosis (>70% in a major epicardial coronary artery) FIGURE 4, Diagnosisof coronaryarterdisease.CAD=coronararterydisease; EF=ejectionfraction; MPI =myocardial perfusionimaging;TlD=transientischemicdilation. 'lntermediate pretesl probabi ity {likelihood) is variably delined as between 1 0% and 90% 0r belween 25"kail75"k. General Approach to Treatment of alternative. Neither prasugrel nor ticagrelor has been studied Stable Angina Pectoris in the context of stable angina, and their role in managing this All patients with angina should receive guideline-directed condition remains to be established. medical therapy comprising risk factor modification (regular Lipid-lowering therapy, targeting LDL cholesterol in par- physical activity, weight loss, tobacco cessation, and dietary ticular, reduces the risk for vascular events and progression of changes), cardioprotective medications to prevent thrombosis and underlying CAD. Statin therapy remains a cornerstone of sec limit atherosclerotic progression, and antianginal medications to ondary prevention because it has been shown to reduce the improve frurctional capacity through reduced cardiac workload risk for MI, death, and stroke. High intensity statin therapy (atorvastatin, 40-80 mg/d, or rosuvastatin, 20-40 mg/d) and/or increased myocardial oxygen delivery (Figure 5 and Figure 6). Blood pressure control (with a goal of <130/80 mm Hg) decreases the LDL cholesterol level by 50'7, or more and is pre

General Approach to Treatment of alternative. Neither prasugrel nor ticagrelor has been studied Stable Angina Pectoris in the context of stable angina, and their role in managing this All patients with angina should receive guideline-directed condition remains to be established. medical therapy comprising risk factor modification (regular Lipid-lowering therapy, targeting LDL cholesterol in par- physical activity, weight loss, tobacco cessation, and dietary ticular, reduces the risk for vascular events and progression of changes), cardioprotective medications to prevent thrombosis and underlying CAD. Statin therapy remains a cornerstone of sec limit atherosclerotic progression, and antianginal medications to ondary prevention because it has been shown to reduce the improve frurctional capacity through reduced cardiac workload risk for MI, death, and stroke. High intensity statin therapy (atorvastatin, 40-80 mg/d, or rosuvastatin, 20-40 mg/d) and/or increased myocardial oxygen delivery (Figure 5 and Figure 6). Blood pressure control (with a goal of <130/80 mm Hg) decreases the LDL cholesterol level by 50'7, or more and is pre and diabetes management should be emphasized. f'erred to moderate intensity therapy fbr secondary preven tion, as higher statin dosing and the resultant lower LDL Cardioprotective Medications cholesterol have been associated with graded improvement in Aspirin reduces the risk for Ml and cardiovascular death in outcomes. In patients with statin intolerance (e.g., those who patients with stable angina. Guidelines recommend low dose develop significant myalgia) or inadequate LDL cholesterol aspirin (75 762 mg/d) for secondary prevention because it is as reduction with statin therapy, it is reasonable to address LDL effective as high-dose aspirin (325 mgid) in preventing MI and cholesterol with nonstatin medications, especially ezetimibe confers a lower bleeding risk. In aspirin intolerant patients, or proprotein convertase subtilisin/kexin type 9 (PCSKg) clopidogrel, a platelet P2Yr2 receptor inhibitor, is an acceptable inhibitors. The addition of icosapent ethyl to statin therapy

and diabetes management should be emphasized. f'erred to moderate intensity therapy fbr secondary preven tion, as higher statin dosing and the resultant lower LDL Cardioprotective Medications cholesterol have been associated with graded improvement in Aspirin reduces the risk for Ml and cardiovascular death in outcomes. In patients with statin intolerance (e.g., those who patients with stable angina. Guidelines recommend low dose develop significant myalgia) or inadequate LDL cholesterol aspirin (75 762 mg/d) for secondary prevention because it is as reduction with statin therapy, it is reasonable to address LDL effective as high-dose aspirin (325 mgid) in preventing MI and cholesterol with nonstatin medications, especially ezetimibe confers a lower bleeding risk. In aspirin intolerant patients, or proprotein convertase subtilisin/kexin type 9 (PCSKg) clopidogrel, a platelet P2Yr2 receptor inhibitor, is an acceptable inhibitors. The addition of icosapent ethyl to statin therapy 14

Coronary Artery Disease HbAr. level >5.7%? BMI :35 kg/m'?? eGFR>45 oGFR <45 mUminl 1.7 3 m2 mU minJ 1 -l 3 m2 level 27 risk and F.sing TG >150 mgy'dL (1.69 mmol/L)? risk? LDL-C rcmains Ml? >70 mmol/L)? BPstill >130/80 Shared No Yes mm Hg? LDI--C rcmains .70mg,/dL(1,81 mmoYLP FIGURE 5. Guideline-directedmedical therapyforpatientswithstableischemicheartdisease(SIHD).ACC=AmericanCollegeof Cardiology; ACEI =ACEinhibitor; AHA= American HeartAssociation; ARB =angiotensin receptor blocker; BB = p-blocker; BID=twice daily; BP = blood pressurei CPAP= continuous positive airway pressure; eGFR = estimated glomerular filtration rate; GLP-1 = glucagon-like peptide 1; HbA,, = hemoglobin A1.; LDL-C = LDI- cholesterol; Ml = myocardial infarction; PCSK9 = proprotein convertase subtilisin/kexin type 9; SG[T2 = sodium-glucose cotransporter 2; TG = triglycerides. Guidelino-directed medical ther.py heart disease o pBlocker (if not prescribed previously) r Sublingual nitroglycorin as needed for angina Continued symptoms Continued symptoms and impaired quality of life . Optimize long-acting and blocker . Consider renolazine Continued symptoms and impaired quality of life

Guidelino-directed medical ther.py heart disease o pBlocker (if not prescribed previously) r Sublingual nitroglycorin as needed for angina Continued symptoms Continued symptoms and impaired quality of life . Optimize long-acting and blocker . Consider renolazine Continued symptoms and impaired quality of life Refer ior coronary angiography F IG U n E 6. Management of stable angina pectoris. pfl = parcutaneous coronary intervention.

Refer ior coronary angiography F IG U n E 6. Management of stable angina pectoris. pfl = parcutaneous coronary intervention. No Recommendations based on tihn SD, GardinJM,AbramsJ, etal; Ameri6n College of Gr Coronary anatomy suitable for PCI diology toundation. 201 2 ACCF/AHA/ACP/MTS/PCNA/sCAI/SIS guideline for the diagnosis or surgical rcvascularization? and management 0f patients with stable isdemi( heaft disease: a reportof theAmelicn College olGrdiology toundation/Ameilcn HeartlssodationTask Force 0n PndiceGuide- Yes lines, and the American College of Physicians,American Association forTholacic Sutgery, Preventive Grdiovas.ular Nu6esfusociation, Society for GrdiovascularAngiography and lnteoentions, and Sodety ol lhoracic Surgeons. J Am Coll Grdiol. 201 2;60:e44-e1 64. IPMID: 231821251 doi:10.1016/ija(c2012.07.013 15 L

Coronary Artery Disease provides further risk reduction in high risk patients with sublingual nitrates should be prescribed for acute reliel of ll,pertriglyceridemia. Management of statin and nonstatin angina. Long acting nitrates, including isosorbide mononitrate lipicl lowering therapies is discussed in MKSAP 19 General or dinitrate and nitroglycerin patch formulations. provide lntern:rl Medicine 1. constant vasodilation. A nitrate free intenal of B to 12 hours. ACE inhibitor therapy is indicated for stable angina if generalll' at night. is needed to avoid derelopment ol nitrate there is concomitant diabetes. chronic kidney disease. left tolerance and reduced efficacy. Side effects include headache. ventricular (LV) dysfunction (ejection fraction <40')1,), heart flushing, and hypotension. Because ofthe risk for h1'potension. lirilure, or history of MI. In these populations. ACE inhibitors concurrent use ofnitrates and phosphodiesterase 5 inhibitors have additional benefits unrelated to CAD, including presen'a (e.g.. sildenafil) is contraindicated. tion of kidney function and improvement in LV function. Ranolazine reduces wall tension and myocardial oxlgen Angiotensin receptor blockers (ARBs) may be used as an alter consumption through inhibition of the late sodium current nativc to ACE inhibitors, although combination therapy is not and subsequent prevention of calcium overload. resulting in indic:rted given the associated increase in ad'r,erse erents reduced angina and increased exercise time. Ranolazine has a without clinical benefit. modest QT prolonging effect but no proarrhlthmic effects. The QT interval should be monitored n'ith co administration Antianginal Medications ofother QT-prolonging drugs, and dose reduction is indicated p I3krckers relieve angina by reducing heart rate, myocardial in patients receiving moderate inhibitors olcltochrome P '150 contractility, and blood pressure. resulting in reduced myocar 3A,1 (CYP3A4), such as verapamil and diltiazem. Ranolazine di:rl oxygen demand. They are recommended as first-line ther should not be used in combination r,r'ith strong CYP3A4 inhib ilpv in patients with stable angina. All B-blockers are equally itors (clarithromycin, itraconazole. ketoconazole, severaI HIV efTicacious in reducing angina. and the choice of p blocker medications) because of resultant increases in ranolazine rr-ray depend on concomitant medical conditions (LV dysfunc serum levels. tion, kidnev dysfunction. lung disease, or significant hyper tension). Dosage should be titrated to achieve a resting heart f,rY POTf,TS rate between 55/min and 60/min. B-Blockers should be used o All patients with coronary artery disease should be n,ith caution in patients taking nondihydropyridine calcium counseled on lifestyle modification. blood pressure channel blockers (verapamil, diltiazem) because of additive control, and management of diabetes mellitus. neqrrtive inotropic and chronotropic effects. Caution also o First-line therapy for stable angina includes aspirin. shoulcl be exercised in the setting of significant conduction statin therapy, and p-blocker therapy. disease or LV dysfunction. B, Selective p blockers. such as o ACE inhibitor therapy is indicated for stable angina with n-retoprolol. are preferred in patients with significant lung concomitant left ventricular dysfunction, heart failure. clisease to avoid worsening respiratory flunction. In patients diabetes mellitus, chronic kidney disease. or history of n'ith reduced LV function. metoprolol succinate, bisoprolol. myocardial infarction. anit canreclilol are associated with reduced long term mortal itll Side eflects include fatigue. lethargl sleep disturbances. irnd impotence. Coronary Revascularization Calcium channel blockers improve myocardial oxygen Decision to Revascularize delivery through coronary vasodilation and reduction in Patients with angina refractory to medical therapy or mark corr)nrrry vilscular resistance while also decreasing myocardial edly abnormal stress testing or coronary CT angiography oxlrgen consumption through antihypertensive and negative results should be considered for invasive coronary angiogra inotropic etTects. These agents can be useful when symptoms phy (see Figure 4). The risks. benefits. and alternatives to persist despite B blocker therapy or when p blockers are not angiography should be discussed along u'ith potential findings tolerated. Shoft-acting dihydropyridine formulations. such as and therapeutic options. The primary goals of revasculariza short acting nifedipine, should be avoided because they can tion in stable syndromes are to lessen angina and improve p:rradoxically worsen angina by acutely lowering blood pres- quality ollife. In contrast, in unstable or acute presentations as sure. resulting in reflex tachycardia and increased myocardial lvell as in stable patients \\,ith high-risk anatomic or clinical oxygen demand. Nondihydropyridine calcium channel block f'eatures (left main CAD, large ischemic burden. and or heart er-s shonld not be used in patients with LV dysfunction because failure). revascularization is indicated for prer,ention of future ot'the increased adverse events associated with their negative events and improved survival. chronotropic and inotropic effects. Revascularization targets are identified based on ana Nitrates improve myocardial oxygen delivery through cor tomic and functional physiotogic characteristics associated onary vasodilation and reduce oxygen demand by reducing with myocardial ischemia. Techniques such as fractional flolv prelold, thereby reducing ventricular wall stress. The benefi reserve and instantaneous wave free ratio provide information cja I etfbcts may be offset by reflex tachycardia unless combined on the f'unctional hemodynamic significance of indeterminate n,itlr F blockers or calcium channel blockers. Short acting lesions identified on angiographic imaging (see Diagnostic

provides further risk reduction in high risk patients with sublingual nitrates should be prescribed for acute reliel of ll,pertriglyceridemia. Management of statin and nonstatin angina. Long acting nitrates, including isosorbide mononitrate lipicl lowering therapies is discussed in MKSAP 19 General or dinitrate and nitroglycerin patch formulations. provide lntern:rl Medicine 1. constant vasodilation. A nitrate free intenal of B to 12 hours. ACE inhibitor therapy is indicated for stable angina if generalll' at night. is needed to avoid derelopment ol nitrate there is concomitant diabetes. chronic kidney disease. left tolerance and reduced efficacy. Side effects include headache. ventricular (LV) dysfunction (ejection fraction <40')1,), heart flushing, and hypotension. Because ofthe risk for h1'potension. lirilure, or history of MI. In these populations. ACE inhibitors concurrent use ofnitrates and phosphodiesterase 5 inhibitors have additional benefits unrelated to CAD, including presen'a (e.g.. sildenafil) is contraindicated. tion of kidney function and improvement in LV function. Ranolazine reduces wall tension and myocardial oxlgen Angiotensin receptor blockers (ARBs) may be used as an alter consumption through inhibition of the late sodium current nativc to ACE inhibitors, although combination therapy is not and subsequent prevention of calcium overload. resulting in indic:rted given the associated increase in ad'r,erse erents reduced angina and increased exercise time. Ranolazine has a without clinical benefit. modest QT prolonging effect but no proarrhlthmic effects. The QT interval should be monitored n'ith co administration Antianginal Medications ofother QT-prolonging drugs, and dose reduction is indicated p I3krckers relieve angina by reducing heart rate, myocardial in patients receiving moderate inhibitors olcltochrome P '150 contractility, and blood pressure. resulting in reduced myocar 3A,1 (CYP3A4), such as verapamil and diltiazem. Ranolazine di:rl oxygen demand. They are recommended as first-line ther should not be used in combination r,r'ith strong CYP3A4 inhib ilpv in patients with stable angina. All B-blockers are equally itors (clarithromycin, itraconazole. ketoconazole, severaI HIV efTicacious in reducing angina. and the choice of p blocker medications) because of resultant increases in ranolazine rr-ray depend on concomitant medical conditions (LV dysfunc serum levels. tion, kidnev dysfunction. lung disease, or significant hyper tension). Dosage should be titrated to achieve a resting heart f,rY POTf,TS rate between 55/min and 60/min. B-Blockers should be used o All patients with coronary artery disease should be n,ith caution in patients taking nondihydropyridine calcium counseled on lifestyle modification. blood pressure channel blockers (verapamil, diltiazem) because of additive control, and management of diabetes mellitus. neqrrtive inotropic and chronotropic effects. Caution also o First-line therapy for stable angina includes aspirin. shoulcl be exercised in the setting of significant conduction statin therapy, and p-blocker therapy. disease or LV dysfunction. B, Selective p blockers. such as o ACE inhibitor therapy is indicated for stable angina with n-retoprolol. are preferred in patients with significant lung concomitant left ventricular dysfunction, heart failure. clisease to avoid worsening respiratory flunction. In patients diabetes mellitus, chronic kidney disease. or history of n'ith reduced LV function. metoprolol succinate, bisoprolol. myocardial infarction. anit canreclilol are associated with reduced long term mortal itll Side eflects include fatigue. lethargl sleep disturbances. irnd impotence. Coronary Revascularization Calcium channel blockers improve myocardial oxygen Decision to Revascularize delivery through coronary vasodilation and reduction in Patients with angina refractory to medical therapy or mark corr)nrrry vilscular resistance while also decreasing myocardial edly abnormal stress testing or coronary CT angiography oxlrgen consumption through antihypertensive and negative results should be considered for invasive coronary angiogra inotropic etTects. These agents can be useful when symptoms phy (see Figure 4). The risks. benefits. and alternatives to persist despite B blocker therapy or when p blockers are not angiography should be discussed along u'ith potential findings tolerated. Shoft-acting dihydropyridine formulations. such as and therapeutic options. The primary goals of revasculariza short acting nifedipine, should be avoided because they can tion in stable syndromes are to lessen angina and improve p:rradoxically worsen angina by acutely lowering blood pres- quality ollife. In contrast, in unstable or acute presentations as sure. resulting in reflex tachycardia and increased myocardial lvell as in stable patients \\,ith high-risk anatomic or clinical oxygen demand. Nondihydropyridine calcium channel block f'eatures (left main CAD, large ischemic burden. and or heart er-s shonld not be used in patients with LV dysfunction because failure). revascularization is indicated for prer,ention of future ot'the increased adverse events associated with their negative events and improved survival. chronotropic and inotropic effects. Revascularization targets are identified based on ana Nitrates improve myocardial oxygen delivery through cor tomic and functional physiotogic characteristics associated onary vasodilation and reduce oxygen demand by reducing with myocardial ischemia. Techniques such as fractional flolv prelold, thereby reducing ventricular wall stress. The benefi reserve and instantaneous wave free ratio provide information cja I etfbcts may be offset by reflex tachycardia unless combined on the f'unctional hemodynamic significance of indeterminate n,itlr F blockers or calcium channel blockers. Short acting lesions identified on angiographic imaging (see Diagnostic 16

t Coronary Artery Disease Testing in Cardiologz), reducing both unnecessary stenting Although guidelines define minimum DAPT duration, the and the need for urgent revascularization. optimal duration should be individualized according to the patient's risks for thrombotic and bleeding complications. Percutaneous Coronary Intervention In patients requiring oral anticoagulation for atrial fibril Percutaneous coronary intervention (PCI) comprises several lation, warfarin or a direct oral anticoagulant (preferred) plus different catheter based techniques to improve coronary clopidogrel can be considered without aspirin, often after 2 to blood flow by relieving coronary obstruction. Following early 4 weeks of triple therapy. In patients with a mechanical valve \ experience with balloon angioplasty and bare metal stenting, prosthesis, warfarin plus clopidogrel therapy is reasonable; I most PCI procedures currently involve second generation direct oral anticoagulants are contraindicated in these patients. drug eluting stent placement, which reduces the risk fbr in In patients undergoing CABG for stable CAD, DAPT for stent restenosis compared with bare metal stenting. 12 months may be reasonable to improve the patency ol vein PCI is indicated to relieve symptoms in patients with grafts. medically refractory angina, those unable to tolerate optimal t( EY P0lltT5 L medical therapy, and those with high risk features on nonin vasive testing. PCI has not been shown to be superior to o The primary goals of revascularization in stable ischemic L guideline directed medical therapy in reducing the risk for syndromes are to lessen angina and improve quality of death or MI in patients with stable angina with or without life. diabetes. o Percutaneous coronary intervention may alleviate angina symptoms but does not decrease mortality or ! Coronary Artery Bypass Graft Surgery risk for myocardial infarction in patients with stable Coronary artery bypass grafting (CABG) with optimal medi angina. cal therapy is generally recommended for patients with . In patients with stable angina who require revasculari multivessel CAD because it results in decreased recurrence zation, coronary artery bypass graft revascularization is of'angina, lower rates of MI, and fewer repeat revasculariza generally preferred to percutaneous coronary interven tion procedures compared with PCI or medical therapy tion in those with left main or three-vessel coronary alone, especially when arterial (internal mammary artery) artery disease or multivessel coronary artery disease plus conduits are utilized. CABC is associated with improved diabetes mellitus. survival in patients lvith left main or three vessel CAD and is indicated in those with multivessel disease and diabetes. . Ten-year survival is improved in patients with coronary artery disease and severe left ventricular dysfunction CABG also improves 10 year survival compared with medi who undergo coronary artery bypass grafting compared cal therapy alone in patients with severe LV dysfunction. with those who receive medical therapy. Although myocardial viability is associated with improved survival and ventricular recovery following revasculariz:r . In patients with stable angina who undergo percutane- tion in patients with LV dysfunction, the role of viability ous coronary intervention, dual antiplatelet therapy testing before revascularization has not been established as should be continued for at least 1 month after bare a predictor of outcome. metal stent placement and at least 6 months after drug eluting stent placement. After Revascularization Aspirin is recommended indef initely after revascularization. 't'he addition of a P2Y,, inhibitor to aspirin (dual antiplatelet Acute Coronary Syndromes therapy [DAPT]) is indicated to reduce risk fbr stent thrombo General Considerations sis and remote ischemic events. DAPT duration depends on An acute coronary syndrome (ACS) results from acute or sub clinical considerations, including patient presentation and acute plaque rupture or erosion and coronary blood flow bleeding and ischemic risks. impairment, manilesting as acute onset chest pain or an ln patients treated with bare metal stent placement, a angina equivalent, often without a clear precipitant. The spec- minimum of 1 month of DAPT is recommended. Current trum of ACS is further characterized by the presence of serum guidelines recommend treating patients with stable angina biomarkers of myocardial injury (elevated troponin T or I). with DAPT for at least 6 months without interruption after Mycicardial injury or MI may be related to an atherothrombotic drug eluting stent placement, with the option to continue event (type 1) or demand/supply mismatch (type 2) (Figure 7). therapy for a longer duration in those with a high risk for ST elevation Ml (STEMI) is differentiated from non thrombosis related complications (e.g., depressed LV func ST elevation acute coronary syndrome (NSTE ACS) by findings tion, saphenous vein graft stenting, and diabetes) and a favora on ECG (Figure 8). The hallmark ECG features of STEMI are ble bleeding profile. In patients at high risk for bleeding, ST segment elevation of at least 1 mm in two or more contigu current evidence supports 3 months of DAPT followed by ous limb or chest leads, although ST segment elevation in lif'elong antiplatelet monotherapy as a reasonable strategz. leads V, and V" must be at least 2 mm in men and at least

Testing in Cardiologz), reducing both unnecessary stenting Although guidelines define minimum DAPT duration, the and the need for urgent revascularization. optimal duration should be individualized according to the patient's risks for thrombotic and bleeding complications. Percutaneous Coronary Intervention In patients requiring oral anticoagulation for atrial fibril Percutaneous coronary intervention (PCI) comprises several lation, warfarin or a direct oral anticoagulant (preferred) plus different catheter based techniques to improve coronary clopidogrel can be considered without aspirin, often after 2 to blood flow by relieving coronary obstruction. Following early 4 weeks of triple therapy. In patients with a mechanical valve \ experience with balloon angioplasty and bare metal stenting, prosthesis, warfarin plus clopidogrel therapy is reasonable; I most PCI procedures currently involve second generation direct oral anticoagulants are contraindicated in these patients. drug eluting stent placement, which reduces the risk fbr in In patients undergoing CABG for stable CAD, DAPT for stent restenosis compared with bare metal stenting. 12 months may be reasonable to improve the patency ol vein PCI is indicated to relieve symptoms in patients with grafts. medically refractory angina, those unable to tolerate optimal t( EY P0lltT5 L medical therapy, and those with high risk features on nonin vasive testing. PCI has not been shown to be superior to o The primary goals of revascularization in stable ischemic L guideline directed medical therapy in reducing the risk for syndromes are to lessen angina and improve quality of death or MI in patients with stable angina with or without life. diabetes. o Percutaneous coronary intervention may alleviate angina symptoms but does not decrease mortality or ! Coronary Artery Bypass Graft Surgery risk for myocardial infarction in patients with stable Coronary artery bypass grafting (CABG) with optimal medi angina. cal therapy is generally recommended for patients with . In patients with stable angina who require revasculari multivessel CAD because it results in decreased recurrence zation, coronary artery bypass graft revascularization is of'angina, lower rates of MI, and fewer repeat revasculariza generally preferred to percutaneous coronary interven tion procedures compared with PCI or medical therapy tion in those with left main or three-vessel coronary alone, especially when arterial (internal mammary artery) artery disease or multivessel coronary artery disease plus conduits are utilized. CABC is associated with improved diabetes mellitus. survival in patients lvith left main or three vessel CAD and is indicated in those with multivessel disease and diabetes. . Ten-year survival is improved in patients with coronary artery disease and severe left ventricular dysfunction CABG also improves 10 year survival compared with medi who undergo coronary artery bypass grafting compared cal therapy alone in patients with severe LV dysfunction. with those who receive medical therapy. Although myocardial viability is associated with improved survival and ventricular recovery following revasculariz:r . In patients with stable angina who undergo percutane- tion in patients with LV dysfunction, the role of viability ous coronary intervention, dual antiplatelet therapy testing before revascularization has not been established as should be continued for at least 1 month after bare a predictor of outcome. metal stent placement and at least 6 months after drug eluting stent placement. After Revascularization Aspirin is recommended indef initely after revascularization. 't'he addition of a P2Y,, inhibitor to aspirin (dual antiplatelet Acute Coronary Syndromes therapy [DAPT]) is indicated to reduce risk fbr stent thrombo General Considerations sis and remote ischemic events. DAPT duration depends on An acute coronary syndrome (ACS) results from acute or sub clinical considerations, including patient presentation and acute plaque rupture or erosion and coronary blood flow bleeding and ischemic risks. impairment, manilesting as acute onset chest pain or an ln patients treated with bare metal stent placement, a angina equivalent, often without a clear precipitant. The spec- minimum of 1 month of DAPT is recommended. Current trum of ACS is further characterized by the presence of serum guidelines recommend treating patients with stable angina biomarkers of myocardial injury (elevated troponin T or I). with DAPT for at least 6 months without interruption after Mycicardial injury or MI may be related to an atherothrombotic drug eluting stent placement, with the option to continue event (type 1) or demand/supply mismatch (type 2) (Figure 7). therapy for a longer duration in those with a high risk for ST elevation Ml (STEMI) is differentiated from non thrombosis related complications (e.g., depressed LV func ST elevation acute coronary syndrome (NSTE ACS) by findings tion, saphenous vein graft stenting, and diabetes) and a favora on ECG (Figure 8). The hallmark ECG features of STEMI are ble bleeding profile. In patients at high risk for bleeding, ST segment elevation of at least 1 mm in two or more contigu current evidence supports 3 months of DAPT followed by ous limb or chest leads, although ST segment elevation in lif'elong antiplatelet monotherapy as a reasonable strategz. leads V, and V" must be at least 2 mm in men and at least 17

Coronary Artery Disease Elevated Cardiac Troponin Value(s) >9fth percentile URL Troponin rise and/or fall Troponin level stable' With acute Without acute ischemiab ischemiab Acute myocardial Acute myocardial Chronic infaraion injury myocardial injury Oxygen supply Atherosclerosis and demand + thrombosis imbalance Type 1 Ml: triggers Type 2 Ml: examples Examples Examples o Plaque rupture . Severe hypertension o Acute heart failure o Structural heart disease . Plaque erosion o Sustained tachyarrhythmia . Myocarditis o Chronic kidney disease FIGURE 7. Amodel{orinterpreting myocardial injur. lschemicthresholdsvarsubstantially in relationtothe magnitudeofthestressorandtheextentofunderlying cardiac disease. Ml= myocardial infarction; URL= upper reference limit. 'Stable denotes <20% variation of trop0nin values in the appropriate clin cal rontext. blschemia denotes signs and/0r symptoms of clinical myocardial ischemia. @201 I The European Society of Cardiology; American College ol Cardioloqy Foundati0n; American Heart I6s0ciation, lnc ; and lhe World Heart Federation.

'Stable denotes <20% variation of trop0nin values in the appropriate clin cal rontext. blschemia denotes signs and/0r symptoms of clinical myocardial ischemia. @201 I The European Society of Cardiology; American College ol Cardioloqy Foundati0n; American Heart I6s0ciation, lnc ; and lhe World Heart Federation. 1.5 mm in women for diagnosis. Posterior MI typically mani bundle branch block may be considered a STEMI equivalent fests as ST segment depression greater than 2 mm in the ante and potentially reflects an acute left anterior descending artery rior leads (V, through V1) with tall R waves, often with occlusion or extensive injury. ST segment elevation in the inferior or lateral leads and NSTE-ACS is categorized according to the presence ofbio ST-segment elevation in posterior leads V, through Vr. New markers of cardiac injury (troponin T or l) in the serum. Non- ST elevation MI is defined as a biomarker positive presentation Acute coronary syndrome that does not meet criteria for STEMI. Unstable angina is charac- (STEMI and NSTE-ACS) terized by new or worsening angina, with or without ECG changes, and without detectable levels of cardiac injury markers.

Acute coronary syndrome that does not meet criteria for STEMI. Unstable angina is charac- (STEMI and NSTE-ACS) terized by new or worsening angina, with or without ECG changes, and without detectable levels of cardiac injury markers. Sl-Elevation Myocardial t nfarction ST-segment elevation Nonspecific ECG changes ST-segment depression Recognition T-wave inversion STEMI typically involves coronary plaque mpture causing platelet adhesion, activation, and aggregation and acute thrombotic occlusion. The sudden transmural myocardial STEMI NSTE-ACS ischemia manifests as ST-segment elevation and signifies the need for rapid initiation ofreperfusion therapy (Figure 9). Although the presentation of STEMI is olten dramatic and Elevated cardiac clear, several diagnoses can mimic STEML Acute pericarditis Normal cardiac troponin levels troponin levels presents with acute chest pain and ST-segment elevation sugges- tive of STEMI. Distinguishing features may include pleuritic or positional pain and diffuse or localized concave ST-segment ele NSTEMI Unstable angina vation with corresponding PR segment depression (Frgure lO). F I G UR E 8, Diagnosis of acute coronary syndromes. NSTE-ACS = non-Sl-elevation Pericarditis and myopericarditis resulting from viral infections acute coronary syndrome; NSIEMI = non-ST-elevation myocardial infarction; or autoimmune conditions can cause cardiac enzyme release, SIEMI = SI'elevation myocardial infarction. further confusing the clinical picture and necessitating a

Sl-Elevation Myocardial t nfarction ST-segment elevation Nonspecific ECG changes ST-segment depression Recognition T-wave inversion STEMI typically involves coronary plaque mpture causing platelet adhesion, activation, and aggregation and acute thrombotic occlusion. The sudden transmural myocardial STEMI NSTE-ACS ischemia manifests as ST-segment elevation and signifies the need for rapid initiation ofreperfusion therapy (Figure 9). Although the presentation of STEMI is olten dramatic and Elevated cardiac clear, several diagnoses can mimic STEML Acute pericarditis Normal cardiac troponin levels troponin levels presents with acute chest pain and ST-segment elevation sugges- tive of STEMI. Distinguishing features may include pleuritic or positional pain and diffuse or localized concave ST-segment ele NSTEMI Unstable angina vation with corresponding PR segment depression (Frgure lO). F I G UR E 8, Diagnosis of acute coronary syndromes. NSTE-ACS = non-Sl-elevation Pericarditis and myopericarditis resulting from viral infections acute coronary syndrome; NSIEMI = non-ST-elevation myocardial infarction; or autoimmune conditions can cause cardiac enzyme release, SIEMI = SI'elevation myocardial infarction. further confusing the clinical picture and necessitating a 18

Coronary Artery Disease STEMI Evaluate: 1. Time from onset of symptoms" 2. High-risk featuresb 3. Time to device therapy with PCI 4. Risks of thrombolytic therapy (contraindications) lnitiate medical therapy: aspirin, p-blocker, nitrates, anticoagulant PCI-capable facility Non-PCl-capable facility Transfer for primary PCI' Administer P2Yl, inhibitord Thrombolytic therapy glycoprotein llb/llla inhibitor (goal s30 min from arrival)' = Administer clopidogrel (300-mg loading dose) PCI (FMC-to-device goal: <90 min for primary PCI)

Administer P2Yl, inhibitord Thrombolytic therapy glycoprotein llb/llla inhibitor (goal s30 min from arrival)' = Administer clopidogrel (300-mg loading dose) PCI (FMC-to-device goal: <90 min for primary PCI) Thrombolytic failure Successful reperfusion Long-term medical therapy: aspirin, P-blocker, ACE inhibitor, high-intensity statin, P2Y,, inhibitor Emergent transfer Urgent transfer for for rescue PCI elective coronary angiography and possible PCll FIGURE 9. Managementof ST-elevationmyocardial infarction(SIEI\41).Fl\4C=firstmedicalcontact; PCI =percutaneousc0r0naryintervention. 'lf )4 hours have elapsed since symptom 0nset, PCI is prefered. bHigh.risk features, such as cardioqenic shock and heart failure, favor PCl. 'F[,4C.to.device ("doorto balloon") goal for patients beinq transle(ed for primary PCI is as soon as possible and <1 20 minutes. dP2Yr2 inhibitore: dopidogrel, prasugrel, ticagrelor.

FIGURE 9. Managementof ST-elevationmyocardial infarction(SIEI\41).Fl\4C=firstmedicalcontact; PCI =percutaneousc0r0naryintervention. 'lf )4 hours have elapsed since symptom 0nset, PCI is prefered. bHigh.risk features, such as cardioqenic shock and heart failure, favor PCl. 'F[,4C.to.device ("doorto balloon") goal for patients beinq transle(ed for primary PCI is as soon as possible and <1 20 minutes. dP2Yr2 inhibitore: dopidogrel, prasugrel, ticagrelor. within 30 minltes 0l h0spital presentati0n ("door to needle time') as a systems goal unless thrombolytic therapy is contraindicated. thrombolytic therapy administration but is ideally performed within 24 hours. CIR 0h013e3182742r{6 thorough history physical examination, and careful study of Patients with accelerated hyper-tension, significant LV the ECG and biomarker release patterns. hypertrophy, and cardiomyopathies may present with chest Acute aortic syndromes can cause ST-segment elevation if pain and elevated cardiac troponin levels caused by elevated I the dissection involves the left or right coronary artery and is LV filling pressures or wall tension with associated subendo- L due to transmural myocardial ischemia. Early recognition is cardial ischemia. The ECG findings are often abnormal in these i essential for this surgical emergency. Diagnostic clues to aortic patients. LV hypertrophy induced ECG changes may look i

thorough history physical examination, and careful study of Patients with accelerated hyper-tension, significant LV the ECG and biomarker release patterns. hypertrophy, and cardiomyopathies may present with chest Acute aortic syndromes can cause ST-segment elevation if pain and elevated cardiac troponin levels caused by elevated I the dissection involves the left or right coronary artery and is LV filling pressures or wall tension with associated subendo- L due to transmural myocardial ischemia. Early recognition is cardial ischemia. The ECG findings are often abnormal in these i essential for this surgical emergency. Diagnostic clues to aortic patients. LV hypertrophy induced ECG changes may look i L dissection include differential blood pressures in the upper similar to ST segment elevation injury currents; however, I extremities, tearing quality of pain with radiation to the back, these changes are tlpically concave in appearance. Comparison I and mediastinal widening on chest radiograph. with previous ECG findings is helpful in identifying acute I Severe hypercalcemia may result in ST segment elevation changes. t L that mimics ACS; however, other findings include a short QT Patients with supraventricular tachycardias, which may t interval and flattened T waves. dramatically increase the rate pressure product, often present I

that mimics ACS; however, other findings include a short QT Patients with supraventricular tachycardias, which may t interval and flattened T waves. dramatically increase the rate pressure product, often present I t I 19 t i

Coronary Artery Disease with chest pain, ST-segment depression, and elevated cardiac Primarg Percutaneous Coronary Interuention enzyme levels, even if no CAD is present. PPCI refers to the process by which an emergency medical provider activates a team of clinicians to initiate emergent Reperfusion coronary angiography and PCI in patients with STEMI. The Prompt reperfusion with primary PCI (PPCD or thrombolytic goal time from first medical contact until PPCI is 9O minutes therapy is indicated in all patients with STEMI who do not or less. Because rates of achieving vessel patenry are higher have limited life expectancy from other nonreversible disease and more reliable with PPCI than with thrombolysis, PPCI is (see Figure 9). Short times to repedusion are correlated with the preferred method of treating STEMI when the patient pre- improved outcome regardless of reperfusion strates/. sents to a PCl-capable hospital or can be transferred from an 20

Coronary Artery Disease TABLE 7. P2Y.2 lnhibitors Used in the Treatment of Patients With CAD Undergoing PCI Drug lndications Loading Dose Maintenance Dose Adverse Effects Contraindications Clopidogrel Stable CAD treated with 300-600 mg 75 mg/d I ncreased Known allergy to the PCI bleeding risk drug ACS Ticagrelor ACS 180 mg 90 mg twice daily" lncreased Known allergy to the bleeding risk, drug \ dyspnea Prasugrel ACS treated with PClb 60 mg 10 mg/d' lncreased Known allergy to bleeding risk the drug, previous transient ischemic attack/stroked, age >-75 y ACS = acute coronary syndrome; CAD = coronary aa(ery disease; PCI = percutaneous coronary ntervent on. Ticagrelor should be used with aspirin, 81 mg/d. "Prasugrel should not be loaded "upstream" (before catheterization). ' Prasugrel, 5 mg/d, shou ld be consrdered for those weighi ng less than 60 k9 ( 1 32 lb). aftack or stroke

ACS = acute coronary syndrome; CAD = coronary aa(ery disease; PCI = percutaneous coronary ntervent on. Ticagrelor should be used with aspirin, 81 mg/d. "Prasugrel should not be loaded "upstream" (before catheterization). ' Prasugrel, 5 mg/d, shou ld be consrdered for those weighi ng less than 60 k9 ( 1 32 lb). aftack or stroke ir.rdex hospital to a PCI capable center quickly (time from first h-rtracerebral hemorrhage is catastrophic, occurring in approx medical contact to PPCI of <120 minutes). Although the initial imately l'1, of patients. Relative and absolute contraindications fbcus of PPCI is on quickly restoring flow to the acutely to thrombolytic therapy are listed in Table 8. occluded artery there is a demonstrable reduction in cardio ln addition to thrombolytic therapy, all patients without vasclllar death and MI end points associated with complete a specific contraindication should receive a loading dose of revascularization compared with culprit only PCI in patients aspirin (162 325 mg) as well as intravenous unfractionated with multivessel disease. The relative benefit associated with heparin, enoxaparin, or fbndaparinux. Clopidogrel loading timing of PCI of nonculprit vessels during the same procedure (300 mg orally) has been demonstrated to increase rates of or within a short interval after PCI of the infarct related vessel vessel patency and is also recommended in this setting. is not established. Prompt transfer to a PCI capable center following throm Patients undergoing PPCI should receive aspirin (t0Z :ZS mg). bolytic therapy (for possible rescue PCI) is reasonable when intravenous unfractionated heparin (with or without glyco this option is available. The ECG should be monitored at 60 to protein IIb/llla blockade) or bivalirudin, and loading doses of 90 minutes to confirm reperfusion, reflected by at least 50'7, additional antiplatelet drugs (P2Yu inhibitors) prior to or upon improvement in maximal ST segment elevation. One quarter arrival in the catheterization laboratory (Table 7). to one third of patients do not achieve reperfusion, particu larly with delayed presentation. Rescue PCI is associated with Thrombolytic Therapy improved outcomes compared with conservative management 'lhrombolytic therapy is recommended for patients with in cases of failed reperfusion. Comnary angiography is recom STEMI when symptom onset is within 12 hours and PPCI is not mended in all patients before discharge, even after successful available within 120 minutes of first medical contact. If symp thrombolysis. tcrnrs began 12 to 24 hours befbre presentation and there is XEY POIilIS evidence of hemodynamic instability or significant myocar . When available in a timely manner, primary percutane- dium at risk (such as with anterior MI), thrombolytic therapy ous coronary intervention is preferred to thromboly'tic should be considered if timely transfer for PPCI (the pref,erred therapy for the treatment of ST elevation myocardial strategy) is not available. Thrombolytic therapy is most inlarction. eftective within the first 3 to 6 hours from symptom onset, after which time fibrin cross linking renders the clot rela r If primary percutaneous coronary intervention (PCI) is tively resistant to lysis. When compared with streptokinase, not available within 120 minutes of first medical con r.rewer fibrin specific thrombolytic agents (alteplase, reteplase, tact, patients with ST elevation myocardial infarction tenecteplase) are associated with improved infarct artery should receive thrombolytic therapy and be transferred patency and fewer allergic reactions, although they are more urgently to a PCl-capable center. costly and have not lowered the risk tbr intracerebral hemor rhage (0.5'){, 0.97,). Complications of STEMI Although thrombolytic therapy is potentially life saving, Arrhythmias are common in the peri infarct setting. Atrial it carries significant risks, primarily related to bleeding. fibrillation, which aftects up to 20'X, of patients with STEMl,

ir.rdex hospital to a PCI capable center quickly (time from first h-rtracerebral hemorrhage is catastrophic, occurring in approx medical contact to PPCI of <120 minutes). Although the initial imately l'1, of patients. Relative and absolute contraindications fbcus of PPCI is on quickly restoring flow to the acutely to thrombolytic therapy are listed in Table 8. occluded artery there is a demonstrable reduction in cardio ln addition to thrombolytic therapy, all patients without vasclllar death and MI end points associated with complete a specific contraindication should receive a loading dose of revascularization compared with culprit only PCI in patients aspirin (162 325 mg) as well as intravenous unfractionated with multivessel disease. The relative benefit associated with heparin, enoxaparin, or fbndaparinux. Clopidogrel loading timing of PCI of nonculprit vessels during the same procedure (300 mg orally) has been demonstrated to increase rates of or within a short interval after PCI of the infarct related vessel vessel patency and is also recommended in this setting. is not established. Prompt transfer to a PCI capable center following throm Patients undergoing PPCI should receive aspirin (t0Z :ZS mg). bolytic therapy (for possible rescue PCI) is reasonable when intravenous unfractionated heparin (with or without glyco this option is available. The ECG should be monitored at 60 to protein IIb/llla blockade) or bivalirudin, and loading doses of 90 minutes to confirm reperfusion, reflected by at least 50'7, additional antiplatelet drugs (P2Yu inhibitors) prior to or upon improvement in maximal ST segment elevation. One quarter arrival in the catheterization laboratory (Table 7). to one third of patients do not achieve reperfusion, particu larly with delayed presentation. Rescue PCI is associated with Thrombolytic Therapy improved outcomes compared with conservative management 'lhrombolytic therapy is recommended for patients with in cases of failed reperfusion. Comnary angiography is recom STEMI when symptom onset is within 12 hours and PPCI is not mended in all patients before discharge, even after successful available within 120 minutes of first medical contact. If symp thrombolysis. tcrnrs began 12 to 24 hours befbre presentation and there is XEY POIilIS evidence of hemodynamic instability or significant myocar . When available in a timely manner, primary percutane- dium at risk (such as with anterior MI), thrombolytic therapy ous coronary intervention is preferred to thromboly'tic should be considered if timely transfer for PPCI (the pref,erred therapy for the treatment of ST elevation myocardial strategy) is not available. Thrombolytic therapy is most inlarction. eftective within the first 3 to 6 hours from symptom onset, after which time fibrin cross linking renders the clot rela r If primary percutaneous coronary intervention (PCI) is tively resistant to lysis. When compared with streptokinase, not available within 120 minutes of first medical con r.rewer fibrin specific thrombolytic agents (alteplase, reteplase, tact, patients with ST elevation myocardial infarction tenecteplase) are associated with improved infarct artery should receive thrombolytic therapy and be transferred patency and fewer allergic reactions, although they are more urgently to a PCl-capable center. costly and have not lowered the risk tbr intracerebral hemor rhage (0.5'){, 0.97,). Complications of STEMI Although thrombolytic therapy is potentially life saving, Arrhythmias are common in the peri infarct setting. Atrial it carries significant risks, primarily related to bleeding. fibrillation, which aftects up to 20'X, of patients with STEMl, 21

Coronary Artery Disease TABLE 8. Contraindications and Cautions for Thrombolytic no treatment. Atrioventricular block, including Wenckebach Thera py i n ST-Elevation Myocardia I nf a rction' I and complete heart block, may occur after inferior infarction' Absolute Contraindications requiring temporary transvenous pacing: howevet perTnanent pacing is rarely required. Benign forms of vagally mediated Any previous intracranial hemorrhage heart block must be differentiated from Mobitz type 2 second Known structural cerebrovascular lesion (e.9., arteriovenous degree atrioventricular block, which is more frequently malformation) observed with anterior infarction and damage to the conduc Known malignant intracranial neoplasm (primary or metastatic) tion system. Mobitz type 2 block may progress to complete lschemic stroke within 3 mo (except acute ischemic stroke heart block and requires permanent pacing. within 4.5 h) Cardiogenic shock, a common complication of STEMI. Suspected aortic dissection typically results from a large anterior MI due to severely Active bleeding or bleeding diathesis (excluding menses) reduced LV systolic function. Cardiogenic shock carries a Significant closed head or facial trauma within 3 mo mortality rate of 5O'2, to 80'7, and must be recognized early. lntracranial or intraspinal surgery within 2 mo Shock is suggested by hypotension, sinus tachycardia. oligu ria, cool extremities, and altered mentation. Untreated car Severe uncontrolled hypertension (unresponsive to emergency therapy) diogenic shock can progress rapidly to end organ failure. such For streptokinase:treatment within the previous 6 mo as acute kidney or liver failure or mesenteric infarction. Patients, particularly those younger than 75 years. ha\€ a Relative Contraindications higher rate ofsurvival ilthey receive emergent revasculariza History of chronic, severe, poorly controlled hypertension tion. An intra aortic balloon pump (IABP). an LV assist device. Severe uncontrolled hypertension on presentation or extracorporeal membrane oxygenation may be used tem (SBP >1 80 mm Hg or DBP >1 10 mm Hg)" porarily, although limited data support their benefit in cardio History of ischemic stroke (>3 mo previously) genic shock. Once the patient is stabilized. weaning the Dementia patient from mechanical and inotropic support and slow Known intracranial abnormality not covered in absolute uptitration of afterload-reducing agents. such as captopril. contra indications can be attempted. p Blockers should be avoided initially and Traumatic or prolonged (>10 min)CPR can be introduced once the patient is hemodynamically sta- Major surgery within 3 wk ble. Diuretics should be used to treat pulmonary vascular congestion. Recent (within 2-4 wk) internal bleeding Approximately 10'/, to 20'2, of cases of anterior STEMI are Noncompressible vascular puncture site complicated by LV apical thrombus. Anticoagulation is gen Pregnancy erally recommended for at least 3 months to reduce the risk Active peptic ulcer disease for systemic embolization, although LV aneurysm without Oral anticoagulant therapy associated thrombus generally is not treated with anticoagu

TABLE 8. Contraindications and Cautions for Thrombolytic no treatment. Atrioventricular block, including Wenckebach Thera py i n ST-Elevation Myocardia I nf a rction' I and complete heart block, may occur after inferior infarction' Absolute Contraindications requiring temporary transvenous pacing: howevet perTnanent pacing is rarely required. Benign forms of vagally mediated Any previous intracranial hemorrhage heart block must be differentiated from Mobitz type 2 second Known structural cerebrovascular lesion (e.9., arteriovenous degree atrioventricular block, which is more frequently malformation) observed with anterior infarction and damage to the conduc Known malignant intracranial neoplasm (primary or metastatic) tion system. Mobitz type 2 block may progress to complete lschemic stroke within 3 mo (except acute ischemic stroke heart block and requires permanent pacing. within 4.5 h) Cardiogenic shock, a common complication of STEMI. Suspected aortic dissection typically results from a large anterior MI due to severely Active bleeding or bleeding diathesis (excluding menses) reduced LV systolic function. Cardiogenic shock carries a Significant closed head or facial trauma within 3 mo mortality rate of 5O'2, to 80'7, and must be recognized early. lntracranial or intraspinal surgery within 2 mo Shock is suggested by hypotension, sinus tachycardia. oligu ria, cool extremities, and altered mentation. Untreated car Severe uncontrolled hypertension (unresponsive to emergency therapy) diogenic shock can progress rapidly to end organ failure. such For streptokinase:treatment within the previous 6 mo as acute kidney or liver failure or mesenteric infarction. Patients, particularly those younger than 75 years. ha\€ a Relative Contraindications higher rate ofsurvival ilthey receive emergent revasculariza History of chronic, severe, poorly controlled hypertension tion. An intra aortic balloon pump (IABP). an LV assist device. Severe uncontrolled hypertension on presentation or extracorporeal membrane oxygenation may be used tem (SBP >1 80 mm Hg or DBP >1 10 mm Hg)" porarily, although limited data support their benefit in cardio History of ischemic stroke (>3 mo previously) genic shock. Once the patient is stabilized. weaning the Dementia patient from mechanical and inotropic support and slow Known intracranial abnormality not covered in absolute uptitration of afterload-reducing agents. such as captopril. contra indications can be attempted. p Blockers should be avoided initially and Traumatic or prolonged (>10 min)CPR can be introduced once the patient is hemodynamically sta- Major surgery within 3 wk ble. Diuretics should be used to treat pulmonary vascular congestion. Recent (within 2-4 wk) internal bleeding Approximately 10'/, to 20'2, of cases of anterior STEMI are Noncompressible vascular puncture site complicated by LV apical thrombus. Anticoagulation is gen Pregnancy erally recommended for at least 3 months to reduce the risk Active peptic ulcer disease for systemic embolization, although LV aneurysm without Oral anticoagulant therapy associated thrombus generally is not treated with anticoagu CPR = cardiopulmonary resuscitation; DBP = diastolic blood pressure; SBP = systolic lation unless other indications. such as atrial fibrillation, are blood pressure. present. nViewed as advisory for clinical decision making and may not be all-inclusive or Right ventricular (RV) infarction, typically identified by definitive. ST segment elevation on right sided ECG Ieads (V, and V1R), Reproduced with permission lrom O'Gara PT, Kushner FG, Ascheim DD, et al. 201 3 ACCF/AHA guideline for the management of ST.elevation myocardial infarction: a can complicate right coronary artery occlusion. Patients pre report of the American College of Card iology Fou ndation/American Heaft sent with hypotension. elevated central venous pressure, and Association Task Force on Practice Guadelines. J Am Coll Cardiol.2013;61:e78 e140. IPM lD: 232 5691 4l doi:1 0.1 01 6/j.jacc.2O12.1 1 .01 9. O201 3 American College of clear lungs. RV dysfunction causes inadequate filling ofthe LV. Cardiology Foundatron and the American Hean Association, lnc. Published by Elsevier lnc. All rights reserued. resulting in shock. Transthoracic echocardiography reveals RV dilatation and dysfunction and may be useful in establishing the diagnosis. Volume resuscitation, inotropes (dobutamine or complicates management and may cause hemodynamic insta dopamine), and RV mechanical support may be necessary to bility. Ventricular tachycardia or fibrillation may occur during bridge to RV recovery which generally takes 2 to 3 days. MI or after reperfusion. Repetitive and sustained bouts of Nitrates are contraindicated because they may worsen hypo- postinfarction ventricular arrhythmias, especially beyond tension by reducing preload. 48 hours, may warrant a longer period of inpatient telemetry LV free nall rupture produces sudden onset chest pain or and predischarge implantable cardioverter defibrillator ther syncope with rapid progression to pulseless electrical activity. apy. Routine suppression of ventricular ectopy with antiar LV free wall rupture is more common in older adults. \ ,omen. rhythmic agents is not recommended and is associated with patients with anterior MI, those receiving anti inflammatory increased arrhythmias and adverse outcomes. In particular, agents, and patients with delayed reperfusion. Surgical, or accelerated idioventricular rhythm, which commonly arises sometimes percutaneous, repair is indicated, but mortality after reperfusion, is generally benign and transient, requiring rates are very high.

CPR = cardiopulmonary resuscitation; DBP = diastolic blood pressure; SBP = systolic lation unless other indications. such as atrial fibrillation, are blood pressure. present. nViewed as advisory for clinical decision making and may not be all-inclusive or Right ventricular (RV) infarction, typically identified by definitive. ST segment elevation on right sided ECG Ieads (V, and V1R), Reproduced with permission lrom O'Gara PT, Kushner FG, Ascheim DD, et al. 201 3 ACCF/AHA guideline for the management of ST.elevation myocardial infarction: a can complicate right coronary artery occlusion. Patients pre report of the American College of Card iology Fou ndation/American Heaft sent with hypotension. elevated central venous pressure, and Association Task Force on Practice Guadelines. J Am Coll Cardiol.2013;61:e78 e140. IPM lD: 232 5691 4l doi:1 0.1 01 6/j.jacc.2O12.1 1 .01 9. O201 3 American College of clear lungs. RV dysfunction causes inadequate filling ofthe LV. Cardiology Foundatron and the American Hean Association, lnc. Published by Elsevier lnc. All rights reserued. resulting in shock. Transthoracic echocardiography reveals RV dilatation and dysfunction and may be useful in establishing the diagnosis. Volume resuscitation, inotropes (dobutamine or complicates management and may cause hemodynamic insta dopamine), and RV mechanical support may be necessary to bility. Ventricular tachycardia or fibrillation may occur during bridge to RV recovery which generally takes 2 to 3 days. MI or after reperfusion. Repetitive and sustained bouts of Nitrates are contraindicated because they may worsen hypo- postinfarction ventricular arrhythmias, especially beyond tension by reducing preload. 48 hours, may warrant a longer period of inpatient telemetry LV free nall rupture produces sudden onset chest pain or and predischarge implantable cardioverter defibrillator ther syncope with rapid progression to pulseless electrical activity. apy. Routine suppression of ventricular ectopy with antiar LV free wall rupture is more common in older adults. \ ,omen. rhythmic agents is not recommended and is associated with patients with anterior MI, those receiving anti inflammatory increased arrhythmias and adverse outcomes. In particular, agents, and patients with delayed reperfusion. Surgical, or accelerated idioventricular rhythm, which commonly arises sometimes percutaneous, repair is indicated, but mortality after reperfusion, is generally benign and transient, requiring rates are very high. 22

Coronary Artery Disease Acquired ventricular septal defect (VSD) from septal wall TABLE 9. TlMl Risk Score for Non-ST-Elevation Acute rupture may complicate infbrior or anterior STEMI, usually in Coronary Syndromes patients with multivessel CAD. VSDs typically occur within Prognostic Variables (1 Point Each) 5 days of STEMI presentation. Patients present with worsening Age >65 y heart failure and shock, and a harsh holosystolic murmur may >3 Traditional CAD risk factorsu be heard at the left lower sternal border. The diagnosis is con firmed with echocardiography. Although initial management Documented CAD with >50% diameter stenosis may include afterload reduction with medical therapy and ST-segment deviation IABP support, the mortality rate in patients with medically >2 Anginal episodes in the past 24 h treated postinfarct VSDs approaches 100'/u. Surgical closure Aspirin use in the past wk should be considered; however, the mortality rate in surgical Elevated cardiac biomarkers (creatine kinase MB ortroponin) series is still high (approximately 50'/.). Patch closure can be very difficult because of the necrotic tissue and inability tr_r TlMl Risk Score (Sum of Prognostic Variables) find viable myocardium to suture and patch. Percutaneous 0-2 Low risk closure with a VSD occluder device is possible but of'ten 3-4 lntermediate risk unsuccessful because of the nature of the defect. and residual 5-7 High risk shunting around the device is common. CAD = coronary artery disease; TlMl = thrombolysis in myocardial infarction. When the posteromedial papillary muscle bloocl supply oHypertension, hypercholesterolemia, diabetes meilitus, being a current smoker f mm the posterior descending artery is interrupted during Ml, family history of CAD. rupture may occur, resulting in severe acute mitral regurgita, lnformation from Antman Et\4, Cohen M, Bernink PJ, et al. The TlMl risk score {or tion several days after STEMI. Afterload reduction and IABP unstable angina/non ST elevation Ml: a method for prognostication and therapeutic decision making. JAMA. 2000;284:835 42. IPMID: 1 093817 2l placement may be temporizing, although urgent surgical doi:1 0. 1 001 /jama.284. 7.835

Acquired ventricular septal defect (VSD) from septal wall TABLE 9. TlMl Risk Score for Non-ST-Elevation Acute rupture may complicate infbrior or anterior STEMI, usually in Coronary Syndromes patients with multivessel CAD. VSDs typically occur within Prognostic Variables (1 Point Each) 5 days of STEMI presentation. Patients present with worsening Age >65 y heart failure and shock, and a harsh holosystolic murmur may >3 Traditional CAD risk factorsu be heard at the left lower sternal border. The diagnosis is con firmed with echocardiography. Although initial management Documented CAD with >50% diameter stenosis may include afterload reduction with medical therapy and ST-segment deviation IABP support, the mortality rate in patients with medically >2 Anginal episodes in the past 24 h treated postinfarct VSDs approaches 100'/u. Surgical closure Aspirin use in the past wk should be considered; however, the mortality rate in surgical Elevated cardiac biomarkers (creatine kinase MB ortroponin) series is still high (approximately 50'/.). Patch closure can be very difficult because of the necrotic tissue and inability tr_r TlMl Risk Score (Sum of Prognostic Variables) find viable myocardium to suture and patch. Percutaneous 0-2 Low risk closure with a VSD occluder device is possible but of'ten 3-4 lntermediate risk unsuccessful because of the nature of the defect. and residual 5-7 High risk shunting around the device is common. CAD = coronary artery disease; TlMl = thrombolysis in myocardial infarction. When the posteromedial papillary muscle bloocl supply oHypertension, hypercholesterolemia, diabetes meilitus, being a current smoker f mm the posterior descending artery is interrupted during Ml, family history of CAD. rupture may occur, resulting in severe acute mitral regurgita, lnformation from Antman Et\4, Cohen M, Bernink PJ, et al. The TlMl risk score {or tion several days after STEMI. Afterload reduction and IABP unstable angina/non ST elevation Ml: a method for prognostication and therapeutic decision making. JAMA. 2000;284:835 42. IPMID: 1 093817 2l placement may be temporizing, although urgent surgical doi:1 0. 1 001 /jama.284. 7.835 intervention usually is indicated. Acute severe mitral regurgi tation also may result lruim l.V dysfunction and is often related to an inferior MI with restriction of the posterior mitral leaflet, Invasive Versus Ischemia-Guided Treatment termed functional ischemic mitral regurgitation. Ischemic Urgent invasive treatment (within 2 hours) is recommended rnitral regurgitation is treated with revascularization and med. for patients with NSTE ACS who have hemodynamic insta ical therapy. bility, refiactory chest pain, heart failure, or ventricular arrhythmias. Non-ST-Elevation Acute Coronary Syndromes In high risk and troponin positive patients with NSTE NSI'E ACS, like SI'EMI, is on the spectrum of acute ischemic ACS who have been initially stabilized, an early invasive strat disorders attributable to plaque erosion or rupture and throm egy improves the composite clinical end point of death, botic occlusion, manifbsting as acute chest pain at rest or with recurrent MI, and repeat hospitalization compared with an minimal exertion. Unlike the complete coronary obstruction ischemia guided approach. In patients with an elevated clini- resulting in STEMI. NSTI-I ACS involves incomplete or tr:rnsient cal risk score, significant S'l segment deviation, or elevated obstruction without ST segment elevation, although ST segment cardiac biomarkers. cardiac catheterization is usually per clepression is often present. formed within 24 hours of presentation. Other patients, including those with diabetes, stage 2 to 3 chronic kidney Risk Stratification disease, LV dysfunction, and recent PCI without elevated risk Initial assessment of suspected NSTE ACS involves a careful scores, may be saf'ely evaluated with coronary angiography history physical examination. ECG. and serial biomarker meas within 72 hours of presentation (delayed invasive strateSr). Llrement to determine the likelihood of a cardiac process. In The choice ol revascularization procedure (PCI or CABG) is patients with lou' likelihoocl of a coronary event, alternative based on the results ofangiography. causes should be investig:rted. In patients with an intermediate With :rn ischemia guided strategy, patients undergo or a high likelihood ol ACS. prognostic assessment with risk noninvasive stress testing ',{,ith LV function assessment scores. such as TIMI and GRACE risk models. is indicated. The before hospital discharge. Cardiac catheterization is reserved simpler of the two models, the TIMI risk score, predicts 14 day for patients with active or intermittent ischemia, including cleath, recurrent MI, and urgent revascularization rates (Table 9). those with angina despite medical therapy or evidence of 'l'he GRACE risk score (www.gracescore.org) incclrporates ischemia on stress testing, and patients at very high clinical examination findings, clinical teatures, ECG findings, and bio risk based on risk score. The ischemia guided approach is nlarker variables (creatinine levels, elevated cardiac enz.ymes) appropriate lbr low risk patients (TlMl score <2 or GRACE kr predict in house and postclischarge death and Ml risk. score <109). particularly low risk women, who may have Prognostic assessment along with serial troponin me:lsure worse outcomes with an early invasive approach. 'fhe rec' ment and clinical status helps determine the most appnrpriate ommendations fbr non low risk women are identical to therapeutic strate$/ (Figure l1). those for men.

intervention usually is indicated. Acute severe mitral regurgi tation also may result lruim l.V dysfunction and is often related to an inferior MI with restriction of the posterior mitral leaflet, Invasive Versus Ischemia-Guided Treatment termed functional ischemic mitral regurgitation. Ischemic Urgent invasive treatment (within 2 hours) is recommended rnitral regurgitation is treated with revascularization and med. for patients with NSTE ACS who have hemodynamic insta ical therapy. bility, refiactory chest pain, heart failure, or ventricular arrhythmias. Non-ST-Elevation Acute Coronary Syndromes In high risk and troponin positive patients with NSTE NSI'E ACS, like SI'EMI, is on the spectrum of acute ischemic ACS who have been initially stabilized, an early invasive strat disorders attributable to plaque erosion or rupture and throm egy improves the composite clinical end point of death, botic occlusion, manifbsting as acute chest pain at rest or with recurrent MI, and repeat hospitalization compared with an minimal exertion. Unlike the complete coronary obstruction ischemia guided approach. In patients with an elevated clini- resulting in STEMI. NSTI-I ACS involves incomplete or tr:rnsient cal risk score, significant S'l segment deviation, or elevated obstruction without ST segment elevation, although ST segment cardiac biomarkers. cardiac catheterization is usually per clepression is often present. formed within 24 hours of presentation. Other patients, including those with diabetes, stage 2 to 3 chronic kidney Risk Stratification disease, LV dysfunction, and recent PCI without elevated risk Initial assessment of suspected NSTE ACS involves a careful scores, may be saf'ely evaluated with coronary angiography history physical examination. ECG. and serial biomarker meas within 72 hours of presentation (delayed invasive strateSr). Llrement to determine the likelihood of a cardiac process. In The choice ol revascularization procedure (PCI or CABG) is patients with lou' likelihoocl of a coronary event, alternative based on the results ofangiography. causes should be investig:rted. In patients with an intermediate With :rn ischemia guided strategy, patients undergo or a high likelihood ol ACS. prognostic assessment with risk noninvasive stress testing ',{,ith LV function assessment scores. such as TIMI and GRACE risk models. is indicated. The before hospital discharge. Cardiac catheterization is reserved simpler of the two models, the TIMI risk score, predicts 14 day for patients with active or intermittent ischemia, including cleath, recurrent MI, and urgent revascularization rates (Table 9). those with angina despite medical therapy or evidence of 'l'he GRACE risk score (www.gracescore.org) incclrporates ischemia on stress testing, and patients at very high clinical examination findings, clinical teatures, ECG findings, and bio risk based on risk score. The ischemia guided approach is nlarker variables (creatinine levels, elevated cardiac enz.ymes) appropriate lbr low risk patients (TlMl score <2 or GRACE kr predict in house and postclischarge death and Ml risk. score <109). particularly low risk women, who may have Prognostic assessment along with serial troponin me:lsure worse outcomes with an early invasive approach. 'fhe rec' ment and clinical status helps determine the most appnrpriate ommendations fbr non low risk women are identical to therapeutic strate$/ (Figure l1). those for men. 23

Coronary Artery Disease Non-ST-elevation acute coronary syndrome (UA/NSTEMI) lnitiate aspirin, p-blocker, nitrates, statin Risk strati{ication High risk lntermediate risk Low risk (TlMl 5-7 or (TlMl 3-4 or (TlMl 0-2 or GRACE 141-372) GRACE 109-140) GRACE 1-108)

High risk lntermediate risk Low risk (TlMl 5-7 or (TlMl 3-4 or (TlMl 0-2 or GRACE 141-372) GRACE 109-140) GRACE 1-108) Early invasive strategy Delayed invasive lschemia-guided (within 24 hours) strategy (25-72 houB) strat6gY . Antiplatelettherapy . Antiplatelettherapy . Antiplatelet therapy (aspirin plus either (aspirin plus either (aspirin plus either clopidogrel or clopidogrel or clopidogrel or ticagrelor',b) ticagrelol. b) ticagrelor,b) . Anticoagulant therapy: . Anticoagulant therapy: . Anticoagulant therapy: UFH or enoxaparin; UFH or enoxaparin; UFH or enoxaparin; selectively, fondaparinux selectively, fondaparinux alternatively, or bivalirudin or bivalirudin fondaparinux . UrgenVimmediate o Consider diagnostic diagnostic coronary coronary angiography' angiography

Early invasive strategy Delayed invasive lschemia-guided (within 24 hours) strategy (25-72 houB) strat6gY . Antiplatelettherapy . Antiplatelettherapy . Antiplatelet therapy (aspirin plus either (aspirin plus either (aspirin plus either clopidogrel or clopidogrel or clopidogrel or ticagrelor',b) ticagrelol. b) ticagrelor,b) . Anticoagulant therapy: . Anticoagulant therapy: . Anticoagulant therapy: UFH or enoxaparin; UFH or enoxaparin; UFH or enoxaparin; selectively, fondaparinux selectively, fondaparinux alternatively, or bivalirudin or bivalirudin fondaparinux . UrgenVimmediate o Consider diagnostic diagnostic coronary coronary angiography' angiography Stress testing

Early invasive strategy Delayed invasive lschemia-guided (within 24 hours) strategy (25-72 houB) strat6gY . Antiplatelettherapy . Antiplatelettherapy . Antiplatelet therapy (aspirin plus either (aspirin plus either (aspirin plus either clopidogrel or clopidogrel or clopidogrel or ticagrelor',b) ticagrelol. b) ticagrelor,b) . Anticoagulant therapy: . Anticoagulant therapy: . Anticoagulant therapy: UFH or enoxaparin; UFH or enoxaparin; UFH or enoxaparin; selectively, fondaparinux selectively, fondaparinux alternatively, or bivalirudin or bivalirudin fondaparinux . UrgenVimmediate o Consider diagnostic diagnostic coronary coronary angiography' angiography Stress testing Normal or low-risk stress Abnormal stress test results test results and no or recurrent symptoms with recurrent chest pain suspected cardiac etiology

Normal or low-risk stress Abnormal stress test results test results and no or recurrent symptoms with recurrent chest pain suspected cardiac etiology Discharge with Coronary follow-up angiography tIGURE ll.lnitial managementof non-ST-elevationacutecoronarysyndromes.NSTEMl=non-ST-elevationmyocardial infarction; UA=unstableangina; UFH = unfractionated heparin. 'Clopidogrel or licagrelor may be administered at the time oi hospital admission and diagnosis oi a(ute coronary syndrome blf coronary artery bypass g(afting is required, dopidogrel or li(agrelor sh0u d be stopped, and surgery should be delayed lor at least 5 days tlf the decisi0n ls made t0 withh0ld a P2Yri inhibitor until the time ol angiography and a P2Yr: inhibitor rs desired, cloprdogrel, ticagrelor, or prasugrel can be nitialed

blf coronary artery bypass g(afting is required, dopidogrel or li(agrelor sh0u d be stopped, and surgery should be delayed lor at least 5 days tlf the decisi0n ls made t0 withh0ld a P2Yri inhibitor until the time ol angiography and a P2Yr: inhibitor rs desired, cloprdogrel, ticagrelor, or prasugrel can be nitialed f,tY ?orilIt Medical Therapy for Acute . Patients with a non ST elevation acute coronary syn Coronary Syndromes drome who have hemodynamic instability, refractory Medical therapies are consistent across the spectrum of chest pain, heart failure, or ventricular arrh,'thmias atherothrombotic ACS (Table lO). However. importantly. require emergent coronary angiography and percutane thrombolytic therapy has no benefit in patients with NSTE ous coronary inlervention. ACS and is not recommended.

f,tY ?orilIt Medical Therapy for Acute . Patients with a non ST elevation acute coronary syn Coronary Syndromes drome who have hemodynamic instability, refractory Medical therapies are consistent across the spectrum of chest pain, heart failure, or ventricular arrh,'thmias atherothrombotic ACS (Table lO). However. importantly. require emergent coronary angiography and percutane thrombolytic therapy has no benefit in patients with NSTE ous coronary inlervention. ACS and is not recommended. r The decision to pursue an invasive versus ischemia All patients presenting with ACS should receive a loading dose of aspirin. supplemental oxygen for oxygen saturation guided approach in patients with a non-ST-elevation less than 90'X, to 92'7,. therapy to relieve symptonls (nitrates). acute coronary s)mdrome is guided by the patient's risk therapy to reduce infarct size (0 blockers. ACE inhibitors), for clinical events, which in turn is determined by deci- high intensity statin therapy, and antithrombotic therapy sion support tools, such as the TIMI or GRACE score. (antiplatelet agents and anticoagulants). 24

Coronary Artery Disease TABLE 10. MedicalTherapy for Acute Coronary Syndromes Medication Drugs in Class Dosage Indications Comments Antiplatelet Medications Aspirin N/A 81-162 mg/d All patients with ACS, unless Non-enteric formulation intolerant or allergic recommended for aspirin- naive patients with ACS Aspiri n desensitization may be considered for patients with allergy Clopidogrel N/A 75 mg/d P2Y12 inhibitor in combination Clopidogrel is with aspirin is indicated in all recommended as an patients after ACS for at least alternative to aspirin for 1y patients with stable CAD and intolerance or allergy to aspirin Prasugrel N/A 10 mg/d P2Y,2 inhibitor in combination Contraindicated with age with aspirin is indicated in all >75 y or history of stroke/ patients after ACS for at least TIA 1 y; prasugrel is indicated only Dosage adjustmentto 5 mg/d in patients with ACS in whom should be considered for PCI is performed patients weighing <60 kg (1321b) Ticagrelor N/A 90 mg twice P2Y12 inhibitor in combination More rapid onset of action; daily with aspirin is indicated in all does not require first-pass patients after ACS for at least hepatic metabolism; 1y no known genetic polymorphisms lncreased risk for bleeding with aspirin doses >100 mg Cardioprotective Medications p-Blockers Atenolol, metoprolol, Variable All patients with prior Ml or Avoid in patients with carvedilol, nebivolol, LV systolic dysfunction (only cardiogenic shock, bisoprolol metoprolol succinate, hypotension, or conduction carvedilol, or bisoprolol) disturbances ACE inhibitors Benazepril, captopril, Variable All patients with LV systolic Particularly beneficial in enalapril, fosinopril, dysfunction, hypertension, patients with anterior Ml perindopril, trandolapril, diabetes mellitus, or kidney lisinopril, ramipril, quinapril disease Angiotensin Losartan, valsartan, Variable All patients with LV systolic Should not be used in receptor blockers olmesartan, candesartan, dysfu nction, hypertension, patients already taking an irbesartan. telmisartan diabetes, or kidney disease ACE inhibitor who are intolerant of ACE inhibitors Aldosterone Eplerenone 25-50 mg/d Patients with sTEMI who Use with caution in patients in hibitor have an LVEF <40% and with chronic kidney disease either clinical heart failure or hyperkalemia or diabetes High-intensity statin Atorvastatin 40-80 mg/d All patients with evidence therapy of CAD and age <75 y Rosuvastatin 20-40 mg/d Moderate-intensity Atorvastatin 10-20 mg/d All patients with evidence Simvastatin dosage should statin therapy of CAD and age >75 y or be limited to 20 mg/d in Rosuvastatin 5-10 mg/d otherwise intolerant of patients taking amlodipine Simvastatin 20-40 mg/d hi gh-i ntensity statin therapy

TABLE 10. MedicalTherapy for Acute Coronary Syndromes Medication Drugs in Class Dosage Indications Comments Antiplatelet Medications Aspirin N/A 81-162 mg/d All patients with ACS, unless Non-enteric formulation intolerant or allergic recommended for aspirin- naive patients with ACS Aspiri n desensitization may be considered for patients with allergy Clopidogrel N/A 75 mg/d P2Y12 inhibitor in combination Clopidogrel is with aspirin is indicated in all recommended as an patients after ACS for at least alternative to aspirin for 1y patients with stable CAD and intolerance or allergy to aspirin Prasugrel N/A 10 mg/d P2Y,2 inhibitor in combination Contraindicated with age with aspirin is indicated in all >75 y or history of stroke/ patients after ACS for at least TIA 1 y; prasugrel is indicated only Dosage adjustmentto 5 mg/d in patients with ACS in whom should be considered for PCI is performed patients weighing <60 kg (1321b) Ticagrelor N/A 90 mg twice P2Y12 inhibitor in combination More rapid onset of action; daily with aspirin is indicated in all does not require first-pass patients after ACS for at least hepatic metabolism; 1y no known genetic polymorphisms lncreased risk for bleeding with aspirin doses >100 mg Cardioprotective Medications p-Blockers Atenolol, metoprolol, Variable All patients with prior Ml or Avoid in patients with carvedilol, nebivolol, LV systolic dysfunction (only cardiogenic shock, bisoprolol metoprolol succinate, hypotension, or conduction carvedilol, or bisoprolol) disturbances ACE inhibitors Benazepril, captopril, Variable All patients with LV systolic Particularly beneficial in enalapril, fosinopril, dysfunction, hypertension, patients with anterior Ml perindopril, trandolapril, diabetes mellitus, or kidney lisinopril, ramipril, quinapril disease Angiotensin Losartan, valsartan, Variable All patients with LV systolic Should not be used in receptor blockers olmesartan, candesartan, dysfu nction, hypertension, patients already taking an irbesartan. telmisartan diabetes, or kidney disease ACE inhibitor who are intolerant of ACE inhibitors Aldosterone Eplerenone 25-50 mg/d Patients with sTEMI who Use with caution in patients in hibitor have an LVEF <40% and with chronic kidney disease either clinical heart failure or hyperkalemia or diabetes High-intensity statin Atorvastatin 40-80 mg/d All patients with evidence therapy of CAD and age <75 y Rosuvastatin 20-40 mg/d Moderate-intensity Atorvastatin 10-20 mg/d All patients with evidence Simvastatin dosage should statin therapy of CAD and age >75 y or be limited to 20 mg/d in Rosuvastatin 5-10 mg/d otherwise intolerant of patients taking amlodipine Simvastatin 20-40 mg/d hi gh-i ntensity statin therapy Pravastati n 40-80 mg/d Lovastatin 40 mg/d Fluvastatin 40 mg twice daily (Continued on the nert page)

Pravastati n 40-80 mg/d Lovastatin 40 mg/d Fluvastatin 40 mg twice daily (Continued on the nert page) 25 t

Coronary Artery Disease TABLE 10. MedicalTherapy for Acute Coronary Syndromes (Continued) Medication Drugs in Class Dosage lndications Comments Antianginal Medications Nitroglycerin Nitrostat (SL) 0.4 mg every 5 min As part of multimodal ity Avoid nitrates with SBP for a total o{ three treatment of ongoing chest <90 mm Hg or >30 mm Hg doses pain below baseline, bradycardia, tachycardia, Nitronal(lV) lnitial lV infusion Persistent chest pain RV infarction, PDE-5 rate of 5-10 pg/min following three SL doses inhibitor use within the last and as part of multimodality 24-48h, HCM, or severe AS treatment of heart failure, hypertension Nondihydropyridine Diltiazem,verapamil Variable PAtiENtS With NSTE-ACS No benefit in patients with calcium channel who are intolerant of STEMI blockers p-blockers or with angina May worsen clinical status refractory to nitrates and with coincidental heart p-blockers fa i u re or LV dysfu ncti on I

TABLE 10. MedicalTherapy for Acute Coronary Syndromes (Continued) Medication Drugs in Class Dosage lndications Comments Antianginal Medications Nitroglycerin Nitrostat (SL) 0.4 mg every 5 min As part of multimodal ity Avoid nitrates with SBP for a total o{ three treatment of ongoing chest <90 mm Hg or >30 mm Hg doses pain below baseline, bradycardia, tachycardia, Nitronal(lV) lnitial lV infusion Persistent chest pain RV infarction, PDE-5 rate of 5-10 pg/min following three SL doses inhibitor use within the last and as part of multimodality 24-48h, HCM, or severe AS treatment of heart failure, hypertension Nondihydropyridine Diltiazem,verapamil Variable PAtiENtS With NSTE-ACS No benefit in patients with calcium channel who are intolerant of STEMI blockers p-blockers or with angina May worsen clinical status refractory to nitrates and with coincidental heart p-blockers fa i u re or LV dysfu ncti on I Avoid with evidence of heart failure, cardiogenic shock, or conduction abnormalities

Avoid with evidence of heart failure, cardiogenic shock, or conduction abnormalities ACS=acutecoronarysyndrome;A5=aorticstenosis;CAD=coronaryarterydisease;HCM=hypenrophrccardiomyopathy;lV=intravenous;LV=leftventricular;LVEF=left

Avoid with evidence of heart failure, cardiogenic shock, or conduction abnormalities ACS=acutecoronarysyndrome;A5=aorticstenosis;CAD=coronaryarterydisease;HCM=hypenrophrccardiomyopathy;lV=intravenous;LV=leftventricular;LVEF=left Antiplatelet Medications In patients undergoing PCI for ACS. especially those with Aspirin (162 325 mg) should be administered at presentation kidney dysfunction, unf'ractionated heparin is favored over to all patients with ACS. followed by a daily dose of 81 to enoxaparin because of the ability to monitor the degree of' 162 mg. Early clopidogrel loading has been recommended in anticoagulation with activated clotting times. Fondaparinux patients with ACS regardless of reperfusion or revasculariza is not indicated during PCI given the risk lor procedural tion strategr, although the optimal timing for loading of other thrombosis. oral antiplatelet agents is less clear. Prasugrel loading before For patients proceeding to the catheterization laboratory, coronary angiography is not beneficial. Clopidogrel or ticagre anticoagulant therapy should be provided until revasculariza Ior therapy is recommended for 1 year after ACS presentation. tion with PCI or CABG. In medically treated patients. antico Prasugrel is indicated only in patients treated with PCI agulation is recommended for at least 48 hours and is generally because it is associated with comparable efficacy but increased continued until discharge. bleeding when compared with clopidogrel in medically man aged patients. Evidence supports continuing DAPT beyond Antianginal Medications 1 year in patients at high risk for recurrent vascular events, Orygen therapy. often considered an antianginal therapy. is such as those with depressed LV function, saphenous vein no longer routinely indicated in ACS. Supplemental oxygen in graft stenting, or diabetes, in whom the benefit exceeds the the setting of normal oxygen saturation is associated with bleeding risk. increased mortality in patients with ACS. Guidelines suggest Intravenous glycoprotein Ilb/llla inhibitors are generally initiating oxygen therapy in patients with oxygen saturation of reserved for use during PCI in patients with evident thrombus at less than 90% to 92"/,, and maintaining saturation at 93'X, to the time of coronary angiography and intervention. In patients 96'l,. The American Heart Association. however, recommends tolerant of DAPT. upfront administration of glycoprotein Ilbrllla oxygen therapy for an oxygen saturation less than 90'7, or in inhibition in the emergency department is associated with lack the presence of heart failure or dyspnea without providing an of benefit and increased bleeding risk, and similarly. there is no upper oxygen saturation limit. proven role for initiation lollowing successful PCI. p Blockers decrease myocardial oxygen demand, reduce the incidence ol ventricular arrhythmias, and improve long Anticoagulant Medications term survival in patients with ACS. These agents should be The choice olanticoagulant during ACS depends on the reper administered orally (not intravenously) within 24 hours of fusion strategy available to the patient. In patients receiving presentation. except in patients with evidence of hypotension, thrombolytic therapy, anticoagulation with unfractionated cardiogenic shock, pulmonary congestion. or atrioventricular heparin, enoxaparin, or fondaparinux is associated with block. reduced reocclusion ofthe infarct related artery and improved Nitrates are used primarily to manage angina symptoms in outcomes. ACS. Sublingual nitrates should be administered at presentation

Antiplatelet Medications In patients undergoing PCI for ACS. especially those with Aspirin (162 325 mg) should be administered at presentation kidney dysfunction, unf'ractionated heparin is favored over to all patients with ACS. followed by a daily dose of 81 to enoxaparin because of the ability to monitor the degree of' 162 mg. Early clopidogrel loading has been recommended in anticoagulation with activated clotting times. Fondaparinux patients with ACS regardless of reperfusion or revasculariza is not indicated during PCI given the risk lor procedural tion strategr, although the optimal timing for loading of other thrombosis. oral antiplatelet agents is less clear. Prasugrel loading before For patients proceeding to the catheterization laboratory, coronary angiography is not beneficial. Clopidogrel or ticagre anticoagulant therapy should be provided until revasculariza Ior therapy is recommended for 1 year after ACS presentation. tion with PCI or CABG. In medically treated patients. antico Prasugrel is indicated only in patients treated with PCI agulation is recommended for at least 48 hours and is generally because it is associated with comparable efficacy but increased continued until discharge. bleeding when compared with clopidogrel in medically man aged patients. Evidence supports continuing DAPT beyond Antianginal Medications 1 year in patients at high risk for recurrent vascular events, Orygen therapy. often considered an antianginal therapy. is such as those with depressed LV function, saphenous vein no longer routinely indicated in ACS. Supplemental oxygen in graft stenting, or diabetes, in whom the benefit exceeds the the setting of normal oxygen saturation is associated with bleeding risk. increased mortality in patients with ACS. Guidelines suggest Intravenous glycoprotein Ilb/llla inhibitors are generally initiating oxygen therapy in patients with oxygen saturation of reserved for use during PCI in patients with evident thrombus at less than 90% to 92"/,, and maintaining saturation at 93'X, to the time of coronary angiography and intervention. In patients 96'l,. The American Heart Association. however, recommends tolerant of DAPT. upfront administration of glycoprotein Ilbrllla oxygen therapy for an oxygen saturation less than 90'7, or in inhibition in the emergency department is associated with lack the presence of heart failure or dyspnea without providing an of benefit and increased bleeding risk, and similarly. there is no upper oxygen saturation limit. proven role for initiation lollowing successful PCI. p Blockers decrease myocardial oxygen demand, reduce the incidence ol ventricular arrhythmias, and improve long Anticoagulant Medications term survival in patients with ACS. These agents should be The choice olanticoagulant during ACS depends on the reper administered orally (not intravenously) within 24 hours of fusion strategy available to the patient. In patients receiving presentation. except in patients with evidence of hypotension, thrombolytic therapy, anticoagulation with unfractionated cardiogenic shock, pulmonary congestion. or atrioventricular heparin, enoxaparin, or fondaparinux is associated with block. reduced reocclusion ofthe infarct related artery and improved Nitrates are used primarily to manage angina symptoms in outcomes. ACS. Sublingual nitrates should be administered at presentation 25

Coronary Artery Disease to relieve chest pain and thereby reduce counterproductive Acute Coronary Syndromes Not Associated sympathetic drive. For patients with persistent chest pain With Obstructive Coronary Artery Disease despite B-blockade, intravenous nitroglycerin can alleviate Some patients with chest pain, elevated cardiac troponin levels. symptoms, particularly in those with hypertension. Patients and characteristic ST segment elevation on ECG have MI in the receiving nitroglycerin infusions for a prolonged time often absence of obstructive CAD (MINOCA). Other related syn require increased doses because of the development of nitrate dromes may mimic MINOCA but do not involve frank infarc- tolerance. Nitrates should be avoided in patients who have had tion. Regardless of whether there is irreversible myocardial recent exposure (within 24 48 hours) to phosphodiesterase 5 injury. treatment of these conditions with thrombolytic agents inhibitors, such as sildenafil. and in those with shock or RV and revascularization in the absence ofocclusive coronary dis- infarction. ease and plaque rupture is not beneficial or recommended. Spontaneous coronary artery dissection (SCAD) is a com- Li p id -Low e r i ng Me d ic at io ns mon cause of chest pain among younger women who present Statin therapy reduces mortality and adverse clinical event with ACS and in the peripartum period. Although the patho- rates after ACS. High-intensity statin therapy is recommended physiologr is not clearly established, SCAD involves develop- because it improves outcomes compared with Iower intensity ment of a nontraumatic and non iatrogenic intramural treatment. Initiating statins in the inpatient setting is associ hematoma with or without intimal dissection with luminal ated with greater medication adherence. Furthermore, statin communication. The enlarging hematoma in the false lumen preloading bef<-rre PCI has been associated with lower rates of compresses the true lumen of the coronary artery and in poten- periprocedural MI. tial combination with obstructing dissection leads to chest pain, ischemia. and/or infarction. Diagnosis requires a high index of Angiotensin Receptor and Aldosterone Agents suspicion and confirmation by invasive or noninvasive angiog ACE inhibitors are indicated in patients with ACS, particularly raphy, using care to minimize unnecessary radiation exposure. those with impaired LV function, heart failure, anterior wall infarction, or diabetes. ARBs may be used in patients intoler When associated with STEMI, SCAD may be managed inva- ant of ACE inhibitors. These agents have shown significant sively; CABG, however, is rarely indicated. PCI may be safely early benefit fbllowing STEMI and should be administered deferred when coronary flow is preserved and symptoms can be within the first 24 hours of presentation in the absence of controlled and closely monitored, because acute vascular contraindications. manipulation often results in dissection extension, and early Eplerenone, an aldosterone antagonist, has proved bene- vascular healing often occurs without further intervention. ficial in patients with STEMI who have an ejection fiaction of Coronary vasospasm is sudden coronary artery constric- 4O"/,, or less and either heart failure or diabetes, especially tion occurring spontaneously or lollowing use of illicit sub when initiated within l week of presentation. Potassium levels stances (methamphetamines, cocaine) or prescription drugs must be monitored carefully, especially in patients with pre- (5 fluorouracil, bromocriptine). Spontaneous coronary vaso existing kidney dysfunction and those receiving concomitant spasm often occurs at night and may occur at rest or following ACE inhibitors or ARBs. exercise. ECG abnormalities may be nonspecific or mimic STEMI patterns. Coronary vasospasm is a diagnosis of exclu rEY POI lIIS sion and often involves coronary angiography to exclude fixed HVC r Thrombolytic therapy is not indicated in patients with disease. Invasive provocative testing can be performed but non-ST elevation acute coronary syndromes. usually is not indicated. Patients suspected of having vaso o All patients presenting with acute coronary syndrome spasm (or the related microvascular endothelial dysfunction) should receive a loading dose of aspirin, supplemental often are treated empirically with nitrates and/or calcium oxygen for oxygen saturation less than 90%, nitrates, a channel blockers. B blockel an ACE inhibitor, a high-intensity statin, a Cardiac syndrome X is a poorly defined condition charac- P2Y,, inhibitor, and an anticoagulant. terized by anginal chest pain in the presence ofangiographi- . Dual antiplatelet therapy is indicated for at least 1 year cally normal coronary arteries or insignificant CAD (<50'1, after acute coronary syndrome (ACS); clopidogrel and stenosis). Several hypotheses have been proposed to explain ticagrelor may be used in all patients with ACS, whereas the pathogenesis of this syndrome, with one of the most prasugrel may be used only in patients treated with per- accepted centering on microvascular dysfunction as the cause. cutaneous coronary intervention. Cardiac syndrome X is a frequent cause of chest pain syn- o p Blockers decrease myocardial oxygen demand, reduce dromes in women and may be associated with adverse out the incidence of ventricular arrhythmias, and improve comes despite the frequent lack of traditional risk factors for long-term survival in patients with acute coronary syn CAD. Patients may be treated with p blockers. calcium chan- drome; however, these agents are contraindicated with nel blockers, nitrates, and ranolazine. cardiogenic shock or high-grade atrioventricular block. Takotsubo cardiomyopathy presents as acute chest pain, ECG changes (often ST-segment elevation), and elevated

to relieve chest pain and thereby reduce counterproductive Acute Coronary Syndromes Not Associated sympathetic drive. For patients with persistent chest pain With Obstructive Coronary Artery Disease despite B-blockade, intravenous nitroglycerin can alleviate Some patients with chest pain, elevated cardiac troponin levels. symptoms, particularly in those with hypertension. Patients and characteristic ST segment elevation on ECG have MI in the receiving nitroglycerin infusions for a prolonged time often absence of obstructive CAD (MINOCA). Other related syn require increased doses because of the development of nitrate dromes may mimic MINOCA but do not involve frank infarc- tolerance. Nitrates should be avoided in patients who have had tion. Regardless of whether there is irreversible myocardial recent exposure (within 24 48 hours) to phosphodiesterase 5 injury. treatment of these conditions with thrombolytic agents inhibitors, such as sildenafil. and in those with shock or RV and revascularization in the absence ofocclusive coronary dis- infarction. ease and plaque rupture is not beneficial or recommended. Spontaneous coronary artery dissection (SCAD) is a com- Li p id -Low e r i ng Me d ic at io ns mon cause of chest pain among younger women who present Statin therapy reduces mortality and adverse clinical event with ACS and in the peripartum period. Although the patho- rates after ACS. High-intensity statin therapy is recommended physiologr is not clearly established, SCAD involves develop- because it improves outcomes compared with Iower intensity ment of a nontraumatic and non iatrogenic intramural treatment. Initiating statins in the inpatient setting is associ hematoma with or without intimal dissection with luminal ated with greater medication adherence. Furthermore, statin communication. The enlarging hematoma in the false lumen preloading bef<-rre PCI has been associated with lower rates of compresses the true lumen of the coronary artery and in poten- periprocedural MI. tial combination with obstructing dissection leads to chest pain, ischemia. and/or infarction. Diagnosis requires a high index of Angiotensin Receptor and Aldosterone Agents suspicion and confirmation by invasive or noninvasive angiog ACE inhibitors are indicated in patients with ACS, particularly raphy, using care to minimize unnecessary radiation exposure. those with impaired LV function, heart failure, anterior wall infarction, or diabetes. ARBs may be used in patients intoler When associated with STEMI, SCAD may be managed inva- ant of ACE inhibitors. These agents have shown significant sively; CABG, however, is rarely indicated. PCI may be safely early benefit fbllowing STEMI and should be administered deferred when coronary flow is preserved and symptoms can be within the first 24 hours of presentation in the absence of controlled and closely monitored, because acute vascular contraindications. manipulation often results in dissection extension, and early Eplerenone, an aldosterone antagonist, has proved bene- vascular healing often occurs without further intervention. ficial in patients with STEMI who have an ejection fiaction of Coronary vasospasm is sudden coronary artery constric- 4O"/,, or less and either heart failure or diabetes, especially tion occurring spontaneously or lollowing use of illicit sub when initiated within l week of presentation. Potassium levels stances (methamphetamines, cocaine) or prescription drugs must be monitored carefully, especially in patients with pre- (5 fluorouracil, bromocriptine). Spontaneous coronary vaso existing kidney dysfunction and those receiving concomitant spasm often occurs at night and may occur at rest or following ACE inhibitors or ARBs. exercise. ECG abnormalities may be nonspecific or mimic STEMI patterns. Coronary vasospasm is a diagnosis of exclu rEY POI lIIS sion and often involves coronary angiography to exclude fixed HVC r Thrombolytic therapy is not indicated in patients with disease. Invasive provocative testing can be performed but non-ST elevation acute coronary syndromes. usually is not indicated. Patients suspected of having vaso o All patients presenting with acute coronary syndrome spasm (or the related microvascular endothelial dysfunction) should receive a loading dose of aspirin, supplemental often are treated empirically with nitrates and/or calcium oxygen for oxygen saturation less than 90%, nitrates, a channel blockers. B blockel an ACE inhibitor, a high-intensity statin, a Cardiac syndrome X is a poorly defined condition charac- P2Y,, inhibitor, and an anticoagulant. terized by anginal chest pain in the presence ofangiographi- . Dual antiplatelet therapy is indicated for at least 1 year cally normal coronary arteries or insignificant CAD (<50'1, after acute coronary syndrome (ACS); clopidogrel and stenosis). Several hypotheses have been proposed to explain ticagrelor may be used in all patients with ACS, whereas the pathogenesis of this syndrome, with one of the most prasugrel may be used only in patients treated with per- accepted centering on microvascular dysfunction as the cause. cutaneous coronary intervention. Cardiac syndrome X is a frequent cause of chest pain syn- o p Blockers decrease myocardial oxygen demand, reduce dromes in women and may be associated with adverse out the incidence of ventricular arrhythmias, and improve comes despite the frequent lack of traditional risk factors for long-term survival in patients with acute coronary syn CAD. Patients may be treated with p blockers. calcium chan- drome; however, these agents are contraindicated with nel blockers, nitrates, and ranolazine. cardiogenic shock or high-grade atrioventricular block. Takotsubo cardiomyopathy presents as acute chest pain, ECG changes (often ST-segment elevation), and elevated 27

Coronary Artery Disease cardiac enzyme levels in the absence of coronary occlusion. erectile dysfunction and decreased satisfaction during sex Takotsubo cardiomyopathy more commonly occurs in women, ual activity are not uncommon following MI. Drug therapy and there is often an antecedent psychological or physical for erectile dysfunction is effective and safe for patients who stressor. It is a diagnosis of exclusion based on lack of signifi- are not taking nitrates (see I\4KSAP 19 General Internal cant coronary stenosis with significant wall motion abnormal Medicine 2). ity (often systolic apical ballooning and notable sparing ofthe Physicians should counsel patients that treatment goals base ofthe heart) on echocardiography or ventriculography. after MI are focused on risk reduction and achieving baseline functional status, although that expectation must be tem- Care After an Acute Coronary Syndrome pered in those with post MI heart failure or significant Ali patients with ACS should continue aspirin, preferably reduction in ejection fraction. Depression after MI is com 81 mg/d, indefinitely. DAPT is recommended for at least l year mon, and screening is recommended; cognitive behavioral (see Table 10). There is some evidence fbr extending DAPT therapy and selective serotonin reuptake inhibitors are first beyond 1 year; however, the decision to prolong therapy should line therapies. be individualized, with the risk for bleeding weighed against the risk fbr thrombosis. rtY PornI Statin therapy should continue indefinitely. Patients with . All patients with acute coronary syndrome should be a history of multiple major atherosclerotic cardiovascular dis referred fbr cardiac rehabilitation. which reduces mor ease (ASCVD) events or one major ASCVD event and multiple tality while improving functional capacity, medication high risk conditions are judged to be at very high risk for adherence, and risk factor profiles. recurrent ASCVD events. These patients may benefit from the addition of nonstatin drug therapy to maximally tolerated statin therapy (see N4KSAP 19 Ceneral Internal Medicine 1). Management of Coronary Artery B Blockers should be continued indefinitely in all patients. ACE inhibitors should be continued indeflnitely in Disease in Specific Populations patients with LV dysfunction and may be beneficial in patients Patients With Asymptomatic Vascular Disease with preserved LV function, especially in those with diabetes. Silent myocardial ischemia is a long recognized syndrome Guidelines recommend avoiding NSAIDs if possible, because with widely varying prevalence and risk estimates, and its of the increased cardiovascular risk associated with these recognition is increasing with the use of diagnostic chest drugs. imaging and dedicated coronary artery calcium scoring stud In patients at risk for sudden cardiac death after MI, guide ies. Although it is clear that patients with silent myocardial iines do not recommend placement of an implantable cardio ischemia, especially those with known underlying heart dis verter defibrillator for primary prevention within 40 days ease, have a worse prognosis, there are no guideline recom of infarction because of lack of benefit. Despite a theoretical mendations on which patients should be evaluated with stress primary prevention benefit in high-risk patients following MI. testing, ambulatory monitoring, or cardiac catheterization nor routine use of a temporary wearable cardioverter defibrillator on how establishing the diagnosis modifles secondary preven has not shown benefit in reducing arrhyhmic death within tion opportunities. 84 days of MI in the large, randomized VEST study. There are no clear indications for a wearable cardioverler defibrillator: Patients Older Than 75 Years however, it is an option for select patients with a high risk for Patients older than 75 years are at heightened cardiovascular sudden death before implantation of a permanent deflbrillator risk because of a higher prevalence and greater severity and device. extent of CAD. Comorbid conditions, loss of muscle mass, and Patients with ACS should be refbrred for cardiac rehabili gait abnormalities often limit or prohibit the use of exercise tation, a medically observed exercise program that reduces stress testing for prognostic and diagnostic purposes. When mortality while improving functional capacity, medication cardiovascular disease is identified. older adults often are not adherence, and risk factor profiies. Patients at low risk (aged treated with recognized secondary prevention therapies (e.g., <75 years with symptoms less than New York Heart Association antiplatelet agents, B-blockers, ACE inhibitors, and statins). functional class III to IV a normal ejection fraction, and no This is at least partly due a perceived heightened risk for arrhythmia) who prefer home based cardiac rehabilitation adverse therapeutic response compounded by the lack of out with remote coaching and indirect exercise supervision ben come data in these patients, who are often excluded from efit as well. prospective trials. Furthermore, invasive angiography and Sexual activity can generally resume after 2 weeks in revascularization are used less often in older adults, likely due younger, previously fit patients with uncomplicated MI and to higher procedural morbidi[z and mortality. Exercise, diet, after 6 weeks in patients with more extensive infarcts, and healthy lifestyle choices remain essential elements of risk assuming other aspects of cardiac rehabilitation are pro reduction in all age groups, with antiplatelet therapy, Iipid ceeding uneventfully. Patients should be counseled that lowering therapy, blood pressure control, and glycemic control

cardiac enzyme levels in the absence of coronary occlusion. erectile dysfunction and decreased satisfaction during sex Takotsubo cardiomyopathy more commonly occurs in women, ual activity are not uncommon following MI. Drug therapy and there is often an antecedent psychological or physical for erectile dysfunction is effective and safe for patients who stressor. It is a diagnosis of exclusion based on lack of signifi- are not taking nitrates (see I\4KSAP 19 General Internal cant coronary stenosis with significant wall motion abnormal Medicine 2). ity (often systolic apical ballooning and notable sparing ofthe Physicians should counsel patients that treatment goals base ofthe heart) on echocardiography or ventriculography. after MI are focused on risk reduction and achieving baseline functional status, although that expectation must be tem- Care After an Acute Coronary Syndrome pered in those with post MI heart failure or significant Ali patients with ACS should continue aspirin, preferably reduction in ejection fraction. Depression after MI is com 81 mg/d, indefinitely. DAPT is recommended for at least l year mon, and screening is recommended; cognitive behavioral (see Table 10). There is some evidence fbr extending DAPT therapy and selective serotonin reuptake inhibitors are first beyond 1 year; however, the decision to prolong therapy should line therapies. be individualized, with the risk for bleeding weighed against the risk fbr thrombosis. rtY PornI Statin therapy should continue indefinitely. Patients with . All patients with acute coronary syndrome should be a history of multiple major atherosclerotic cardiovascular dis referred fbr cardiac rehabilitation. which reduces mor ease (ASCVD) events or one major ASCVD event and multiple tality while improving functional capacity, medication high risk conditions are judged to be at very high risk for adherence, and risk factor profiles. recurrent ASCVD events. These patients may benefit from the addition of nonstatin drug therapy to maximally tolerated statin therapy (see N4KSAP 19 Ceneral Internal Medicine 1). Management of Coronary Artery B Blockers should be continued indefinitely in all patients. ACE inhibitors should be continued indeflnitely in Disease in Specific Populations patients with LV dysfunction and may be beneficial in patients Patients With Asymptomatic Vascular Disease with preserved LV function, especially in those with diabetes. Silent myocardial ischemia is a long recognized syndrome Guidelines recommend avoiding NSAIDs if possible, because with widely varying prevalence and risk estimates, and its of the increased cardiovascular risk associated with these recognition is increasing with the use of diagnostic chest drugs. imaging and dedicated coronary artery calcium scoring stud In patients at risk for sudden cardiac death after MI, guide ies. Although it is clear that patients with silent myocardial iines do not recommend placement of an implantable cardio ischemia, especially those with known underlying heart dis verter defibrillator for primary prevention within 40 days ease, have a worse prognosis, there are no guideline recom of infarction because of lack of benefit. Despite a theoretical mendations on which patients should be evaluated with stress primary prevention benefit in high-risk patients following MI. testing, ambulatory monitoring, or cardiac catheterization nor routine use of a temporary wearable cardioverter defibrillator on how establishing the diagnosis modifles secondary preven has not shown benefit in reducing arrhyhmic death within tion opportunities. 84 days of MI in the large, randomized VEST study. There are no clear indications for a wearable cardioverler defibrillator: Patients Older Than 75 Years however, it is an option for select patients with a high risk for Patients older than 75 years are at heightened cardiovascular sudden death before implantation of a permanent deflbrillator risk because of a higher prevalence and greater severity and device. extent of CAD. Comorbid conditions, loss of muscle mass, and Patients with ACS should be refbrred for cardiac rehabili gait abnormalities often limit or prohibit the use of exercise tation, a medically observed exercise program that reduces stress testing for prognostic and diagnostic purposes. When mortality while improving functional capacity, medication cardiovascular disease is identified. older adults often are not adherence, and risk factor profiies. Patients at low risk (aged treated with recognized secondary prevention therapies (e.g., <75 years with symptoms less than New York Heart Association antiplatelet agents, B-blockers, ACE inhibitors, and statins). functional class III to IV a normal ejection fraction, and no This is at least partly due a perceived heightened risk for arrhythmia) who prefer home based cardiac rehabilitation adverse therapeutic response compounded by the lack of out with remote coaching and indirect exercise supervision ben come data in these patients, who are often excluded from efit as well. prospective trials. Furthermore, invasive angiography and Sexual activity can generally resume after 2 weeks in revascularization are used less often in older adults, likely due younger, previously fit patients with uncomplicated MI and to higher procedural morbidi[z and mortality. Exercise, diet, after 6 weeks in patients with more extensive infarcts, and healthy lifestyle choices remain essential elements of risk assuming other aspects of cardiac rehabilitation are pro reduction in all age groups, with antiplatelet therapy, Iipid ceeding uneventfully. Patients should be counseled that lowering therapy, blood pressure control, and glycemic control 28

Coronary Artery Disease of benefit in patients at suitable risk. regardless ol age. Medical Therapy and Secondary Prevention Hyperlipidemia remains associated with adverse outcomes in Optimal medical therapy, including aggressive risk factor the elderly, with a recent meta analysis of primary and sec reduction. glucose control, and antianginal therapy. is founda ondary prevention trials demonstrating reduction in cardiac tional for patients with diabetes and CAD. Although specific events and disabiliry in this group. blood pressure goals remain controversial, a blood pressure goal ofl less than l4Ol90 mm Hg provides a balance of safety Women and efficacy for most patients with diabetes. The American Clinical Presentation Diabetes Association (ADA) recommends a blood pressure Women usually develop ischemic heart disease at an older age target of less than 140/90 mm Hg in patients at lower risk for than men and more commonly present with stable CAD than ASCVD and suggests that a blood pressure target ofless than ACS. In women with typical angina symptoms, nonobstructive 130,80 mm Hg may be appropriate for patients with either coronary stenoses are present on coronary angiography in existing ASCVD or a l0 year ASCVD risk of lS'X, or greater. if more than 50'7, of cases, and microvascular dysfunction it can be achieved without undue treatment burden. The (endothelium-dependent or endothelium independent) is American College of Cardiologr/American Heart Association thought to be a predominant cause of symptoms in these guidelines recommend antihypertensive treatment \ rith a tar patients. In women with acute MI. the predominant symptom get blood pressure below 130/80 mm Hg in patients \(ith dia- is chest pain or pressurei however, women can have atypical betes. ACE inhibitors or ARBs are the preferred antihyperten symptoms, such as fatigue, dyspnea. nausea, or abdominal sive therapies given their renal protective effects. High intensity symptoms. statin therapy is indicated in patients with diabetes and CAD. Several unique manifestations of cardiovascular disease, with the addition of ezetimibe or PCSK9 inhibitors as needed including SCAD, takotsubo cardiomyopathy, and coronary for optimal lipid control. vasospasm. occur primarily in women. Aspirin is recommended for secondary prevention in all patients with diabetes and CAD. The role of P2Y,, inhibition Evaluation and Treatment (clopidogrel or ticagrelor) with or without aspirin continues to Diagnostic and therapeutic recommendations for CAD do not evolve, with evidence supporting a secondary prevention ben- differ for men and women. Noninvasive stress testing has a efit at the expense of excess bleeding. lower sensitivity and specificity in women than in men, and Tight glycemic control reduces microvascular compli- exertional ST segment deviation has a lower reported accuracy cations but does not reduce the risk lor Ml. particularly in women. when initiated late in the disease course. The use of sodium Reports from observational studies and secondary analy glucose cotransporter 2 (SGLT2) inhibitors or glucagon like sis of randomized controlled trials suggest that women have peptide 1 (GLP 1) receptor agonists in patients with type 2 worse outcomes after STEMI presentation. possibly due to diabetes reduces rates ofacute MI, stroke, and cardiovascu delays in recognition and longer ischemic time, as well as a lar death. Based on strong evidence. the ADA recommends recognized increase in complication rates after reperfusion introducing an SGLT2 inhibitor or a GLP I receptor agonist therapy for STEMI. with demonstrated cardiovascular disease benefit as part of a glycemic control regimen in patients r.t,ith type 2 diabetes Patients With Diabetes Mellitus and clinical ASCVD. If the patient is already taking met Risk and Evaluation formin combined with another therapeutic agent or agents Diabetes is associated with a two to threefold increase in age and not taking an SGLT2 inhibitor or GLP I receptor ago adjusted risk for CAD events, including cardiovascular mortal nist. the ADA recommends considering switching to one of ity. This increased risk is multifactorial and is associated with these agents. a higher incidence of cardiovascular risk factors as well as underlying vascular and myocardial dysfunction accompany Invasive Treatment ing the diabetic state. Outcome following both surgical and percutaneous revas- Evaluation and diagnostic strategy for CAD are similar cularization is impaired in patients with diabetes. The in patients with or without diabetes. although cardiac choice of revascularization strategv is based on the severity symptoms such as dyspnea and nausea are more common. and extent of CAD. comorbid conditions. and patient pref requiring a high index of suspicion in at risk patients. The erence. recognizing that CABG is associated with improved diagnostic accuracy of noninvasive stress testing in sympto outcomes, including lower rates of repeat revascularization matic patients with diabetes is similar to that in patients and the composite of death. MI. or stroke. Regardless of the without diabetes. Although traditional CAD risk factors strateg), employed. optimal technique is essential. including should be aglressively managed in all patients with diabetes. drug eluting stent placement in PCI and arterial conduit screening for CAD in asymptomatic persons is controversial use in CABG. Optimal medical therapy has been shown to and without proven outcome beneflt: thus, routine stress provide lasting benefit independent of revascularization testing is not recommended. modality.

of benefit in patients at suitable risk. regardless ol age. Medical Therapy and Secondary Prevention Hyperlipidemia remains associated with adverse outcomes in Optimal medical therapy, including aggressive risk factor the elderly, with a recent meta analysis of primary and sec reduction. glucose control, and antianginal therapy. is founda ondary prevention trials demonstrating reduction in cardiac tional for patients with diabetes and CAD. Although specific events and disabiliry in this group. blood pressure goals remain controversial, a blood pressure goal ofl less than l4Ol90 mm Hg provides a balance of safety Women and efficacy for most patients with diabetes. The American Clinical Presentation Diabetes Association (ADA) recommends a blood pressure Women usually develop ischemic heart disease at an older age target of less than 140/90 mm Hg in patients at lower risk for than men and more commonly present with stable CAD than ASCVD and suggests that a blood pressure target ofless than ACS. In women with typical angina symptoms, nonobstructive 130,80 mm Hg may be appropriate for patients with either coronary stenoses are present on coronary angiography in existing ASCVD or a l0 year ASCVD risk of lS'X, or greater. if more than 50'7, of cases, and microvascular dysfunction it can be achieved without undue treatment burden. The (endothelium-dependent or endothelium independent) is American College of Cardiologr/American Heart Association thought to be a predominant cause of symptoms in these guidelines recommend antihypertensive treatment \ rith a tar patients. In women with acute MI. the predominant symptom get blood pressure below 130/80 mm Hg in patients \(ith dia- is chest pain or pressurei however, women can have atypical betes. ACE inhibitors or ARBs are the preferred antihyperten symptoms, such as fatigue, dyspnea. nausea, or abdominal sive therapies given their renal protective effects. High intensity symptoms. statin therapy is indicated in patients with diabetes and CAD. Several unique manifestations of cardiovascular disease, with the addition of ezetimibe or PCSK9 inhibitors as needed including SCAD, takotsubo cardiomyopathy, and coronary for optimal lipid control. vasospasm. occur primarily in women. Aspirin is recommended for secondary prevention in all patients with diabetes and CAD. The role of P2Y,, inhibition Evaluation and Treatment (clopidogrel or ticagrelor) with or without aspirin continues to Diagnostic and therapeutic recommendations for CAD do not evolve, with evidence supporting a secondary prevention ben- differ for men and women. Noninvasive stress testing has a efit at the expense of excess bleeding. lower sensitivity and specificity in women than in men, and Tight glycemic control reduces microvascular compli- exertional ST segment deviation has a lower reported accuracy cations but does not reduce the risk lor Ml. particularly in women. when initiated late in the disease course. The use of sodium Reports from observational studies and secondary analy glucose cotransporter 2 (SGLT2) inhibitors or glucagon like sis of randomized controlled trials suggest that women have peptide 1 (GLP 1) receptor agonists in patients with type 2 worse outcomes after STEMI presentation. possibly due to diabetes reduces rates ofacute MI, stroke, and cardiovascu delays in recognition and longer ischemic time, as well as a lar death. Based on strong evidence. the ADA recommends recognized increase in complication rates after reperfusion introducing an SGLT2 inhibitor or a GLP I receptor agonist therapy for STEMI. with demonstrated cardiovascular disease benefit as part of a glycemic control regimen in patients r.t,ith type 2 diabetes Patients With Diabetes Mellitus and clinical ASCVD. If the patient is already taking met Risk and Evaluation formin combined with another therapeutic agent or agents Diabetes is associated with a two to threefold increase in age and not taking an SGLT2 inhibitor or GLP I receptor ago adjusted risk for CAD events, including cardiovascular mortal nist. the ADA recommends considering switching to one of ity. This increased risk is multifactorial and is associated with these agents. a higher incidence of cardiovascular risk factors as well as underlying vascular and myocardial dysfunction accompany Invasive Treatment ing the diabetic state. Outcome following both surgical and percutaneous revas- Evaluation and diagnostic strategy for CAD are similar cularization is impaired in patients with diabetes. The in patients with or without diabetes. although cardiac choice of revascularization strategv is based on the severity symptoms such as dyspnea and nausea are more common. and extent of CAD. comorbid conditions. and patient pref requiring a high index of suspicion in at risk patients. The erence. recognizing that CABG is associated with improved diagnostic accuracy of noninvasive stress testing in sympto outcomes, including lower rates of repeat revascularization matic patients with diabetes is similar to that in patients and the composite of death. MI. or stroke. Regardless of the without diabetes. Although traditional CAD risk factors strateg), employed. optimal technique is essential. including should be aglressively managed in all patients with diabetes. drug eluting stent placement in PCI and arterial conduit screening for CAD in asymptomatic persons is controversial use in CABG. Optimal medical therapy has been shown to and without proven outcome beneflt: thus, routine stress provide lasting benefit independent of revascularization testing is not recommended. modality. 29