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General Principles in Older Adults
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ACS has 3 components: ST-segment elevation myocardial infarction (STEMI), non–ST-segment elevation myocardial infarction (NSTEMI), and unstable angina (UA). All 3 share a common pathophysiologic origin related to progression of coronary plaque, instability, and rupture. STEMI refers to the elevation of the ST segment in at least 2 contiguous leads along with either biomarker evidence (troponin I or T; creatine kinase, myocardial bound [CK-MB]; myoglobin) of myocardial necrosis or symptoms consistent with ischemia. NSTEMI has a similar definition, but without elevation of the ST segment in at least 2 contiguous leads. UA is chest pain or discomfort that is accelerating in frequency or severity and can occur at rest, but does not result in myocardial damage as noted by negative cardiac biomarkers. Patients with UA are at increased risk for progression to myocardial infarction (MI). The percentage of ACS composed of STEMI varies from 29% to 47% but has been decreasing over time.
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Of the estimated 1.2 million MIs or fatal coronary heart disease (CHD) events occurring annually in the United States, 67% occur in persons older than age 65 years and 44% occur in persons older than age 75 years. Older patients are more likely to have NSTEMI than STEMI. Case fatality rates increase markedly with age; 80% of all MI deaths occur in persons older than age 65 years. Although the incidence of MI is higher in men than in women at all ages, the total number of MIs or fatal CHD events is greater in women than men older than age 75 years, reflecting the fact that the proportion of women in the surviving population increases with age. The prevalence of silent or clinically unrecognized MI increases with age and prevalence may be twice as high as recognized MI in older adults. The long-term prognosis after clinically unrecognized MI is similar to that of recognized MI in older adults.
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Despite the high prevalence of CHD and ACS in industrialized countries, these disorders are potentially preventable or can be delayed through early and aggressive management of risk factors as discussed above. Although some risk factors, such as age, sex, and genetics, cannot be modified, lifelong adherence to behavior modification, including regular physical exercise; maintenance of desirable body weight; a diet rich in fruits, vegetables, and whole-grains but low in trans and saturated fats; and avoidance of tobacco products, can significantly reduce this risk.
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Aspirin, adenosine diphosphatase (ADP) receptor antagonists, β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and statins have been shown to improve post-ACS prognosis. In addition, cardiac rehabilitation programs also reduce mortality and rehospitalizations after ACS.
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The proportion of MI patients who have chest pain declines with age; <50% of MI patients older than 80 years complain of chest pain. Likewise, diaphoresis occurs less frequently in older patients with acute MI. Dyspnea is often the presenting manifestation of acute MI in older adults and is the most common initial symptom in persons older than 80 years. The prevalence of atypical symptoms (eg, gastrointestinal disturbances, overwhelming fatigue, dizziness, syncope, confusion, stroke) also increases with age, and up to 20% of patients older than 85 years with acute MI have neurologic complaints (see Chapter 63, “Addressing Chest Pain in Older Adults”).
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Physical findings associated with ACS are nonspecific but may include signs of acute heart failure, occurring in up to 40% of older patients with MI. These signs include an S3 or S4 gallop, new mitral regurgitation murmur, or signs of pulmonary or systemic venous congestion, such as pulmonary rales or elevated jugular venous pressure (JVP). In patients with right ventricular infarction, the Kussmaul sign (rise in JVP with inspiration) may be present.
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Classic electrocardiographic features of a STEMI are ST-segment elevation of at least 1 mm in 2 or more contiguous leads corresponding to the anatomical distribution of a coronary artery (eg, leads II, III, avF), often with subsequent evolution to pathologic Q waves or new left bundle-branch block. ST elevation is not present in NSTEMI or UA, but there can be ST-segment depression or T-wave inversion, or both. Electrocardiographic changes often resolve with resolution of chest pain, so a nondiagnostic or even normal electrocardiogram (ECG) taken when the patient is free of symptoms does not exclude ischemia. However, the initial ECG is often nondiagnostic in older adults because of preexisting conduction system disease (eg, left bundle-branch block), presence of a ventricular pacemaker, prior infarct, left ventricular hypertrophy, metabolic abnormalities, or drug effects (eg, hypokalemia, digoxin), and the high prevalence of NSTEMI.
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Atypical symptoms and physical findings, coupled with the high prevalence of nondiagnostic ECGs, often lead to delayed presentation and recognition of ACS. This time lag increases the risk of complications and reduces the window of opportunity for timely and effective intervention. Clinicians should maintain a high index of suspicion for ACS in all older patients with a wide range of unexplained symptoms and/or significant physical distress.
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Definitive diagnosis of STEMI or NSTEMI requires abnormal cardiac biomarker elevation. Troponins I and T have become the gold standard for diagnosis because of their greater sensitivity and specificity compared with the CK-MB isoenzyme. Serial measures of biomarkers that exceed the normal range and exhibit a typical rise-and-fall pattern in a patient with clinical and/or electrocardiographic features of cardiac ischemia are diagnostic of MI. In the absence of recurrent ischemia, CK-MB levels rise within 4–6 hours, peak at approximately 24 hours after MI onset and return to normal within 36–48 hours. Troponin levels rise within 2–3 hours of onset of symptoms, peak at 24–72 hours, and may remain elevated for up to 10–14 days, especially in large infarctions.
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Differential Diagnosis
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The differential diagnosis of ACS in older adults includes other cardiovascular conditions as well as pulmonary, gastrointestinal, musculoskeletal, and neurologic disorders. Important cardiovascular conditions that should be considered include aortic dissection, pericarditis, myocarditis, acute pulmonary edema resulting from cardiomyopathy, valvular heart disease, and arrhythmia. Pulmonary disorders include pneumonia, pulmonary embolus, pneumothorax, pleurisy, and pleural effusion. Gastrointestinal disorders include esophagitis, esophageal spasm, esophageal rupture, gastroesophageal reflux, peptic ulcer disease, cholelithiasis, and pancreatitis. Musculoskeletal disorders include muscular strains, costochondritis, injuries involving the cervical or thoracic spine, disorders of the shoulder joint, and chest wall trauma. Neurologic conditions include stroke or transient ischemic attack, radiculopathy, and altered sensorium or delirium. Psychogenic conditions, including anxiety and hyperventilation syndrome, may also mimic the ACS symptoms.
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Major MI complications include acute heart failure, conduction disturbances (eg bundle branch block, advanced atrioventricular [AV] block), atrial fibrillation, myocardial rupture, sudden death and cardiogenic shock. Each complication is associated with worse prognosis and occurs 2–4 times more frequently in older patients.
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Table 28–2 lists the major therapeutic options for ACS. Management of STEMI and NSTEMI differs with respect to the use of early reperfusion therapy but is otherwise similar. For UA, the primary goals of therapy are symptom relief and preventing progression to NSTEMI or STEMI. Guidelines recommend that older patients receive the same treatment as younger patients with close monitoring for adverse events and with the caution that their general health, comorbidities, cognitive status, and life expectancy be taken into account and that increased sensitivity to hypotension-inducing drugs and possible altered pharmacokinetics be considered.
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Maintenance of adequate arterial oxygenation and relief of chest discomfort are important goals. Intravenous morphine should be administered every 5–30 minutes as needed for relief of chest pain, monitoring closely for signs of respiratory depression, bradycardia, hypotension, and impaired sensorium, all of which are more common in older adults. Sublingual nitroglycerin should be administered acutely for the treatment of ischemic chest pain or dyspnea.
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Patients with persistent chest pain or signs of pulmonary congestion should receive topical nitroglycerin ointment or an intravenous nitroglycerin infusion, titrated to control symptoms while avoiding excessive blood pressure (BP) reduction. In patients with signs of right ventricular infarction (ST elevation or depression in right precordial or inferior leads with elevated JVP and Kussmaul sign), nitroglycerin should be avoided as it may precipitate severe hypotension.
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Recanalization of the involved coronary artery as quickly as possible reduces mortality and morbid MI complications. Reperfusion can be achieved either pharmacologically with fibrinolytics or mechanically with percutaneous coronary intervention (PCI) with stent implantation. In general, mechanical reperfusion is more effective than fibrinolysis if it can be achieved in a timely manner. The recommended time from hospital presentation to reperfusion is 90 minutes.
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Mechanical reperfusion has a lower risk of intracranial hemorrhage, particularly in patients older than 75 years, in whom the risk of intracranial bleeding is 1% to 2% with fibrinolysis. Mechanical reperfusion benefits patients with both STEMI and NSTEMI, whereas fibrinolytic therapy is only effective in STEMI and is contraindicated in treatment of NSTEMI.
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Patients with UA who have severe or recurrent symptoms or electrocardiographic abnormalities should undergo coronary angiography followed by percutaneous or surgical revascularization based on anatomic findings. Patients who respond to medical therapy and have no further symptoms should undergo a symptom-limited stress test for risk stratification. Patients with severe ischemia, ischemia at low cardiac workload, or ischemia in association with reduced left ventricle (LV) systolic function should proceed to angiography and possibly revascularization. Those with less-severe ischemia or a normal stress test may be managed medically.
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The 5 fibrinolytic agents approved for intravenous use for the treatment of STEMI in the United States are streptokinase, alteplase, anistreplase, reteplase, and tenecteplase. Use of fibrinolytic agents should be restricted to those who fulfill criteria for fibrinolysis and can be treated within 6 hours of symptom onset (Table 28–3). In-hospital mortality increases with increasing age along with the risk of intracranial hemorrhage and ventricular free wall rupture in older patients receiving fibrinolytics.
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Mechanical reperfusion (ie, PCI with or without stenting) is associated with improved outcomes in patients of all ages and is superior to fibrinolysis in older patients. Either bare metal stents or drug-eluting stents may be implanted. The latter are generally preferred, given the lower risk of restenosis, although they require a longer duration of treatment with dual antiplatelet agents. Early angiography and coronary intervention is associated with improved short- and long-term outcomes in patients with either STEMI or NSTEMI. In STEMI patients, the target door-to-balloon time is 90 minutes. Mechanical reperfusion, if available, is the preferred strategy in older patients with documented ACS, although used less often than in younger patients. Older patients do have a lower rate of angiographic success and less ST-segment resolution and more postinfarction complications.
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Antithrombotic Therapy
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Aspirin is indicated for all patients with ACS. It is effective in older adults and should be continued indefinitely in all patients with documented CHD. The recommended dosage in the acute setting of ACS is 325 mg daily; dosages of 75–325 mg daily are suitable for long-term use.
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Anticoagulation is indicated in patients with NSTEMI and UA, although the benefits in STEMI are less well-established. Its benefit is even greater in ACS complicated by recurrent ischemia or atrial fibrillation. Anticoagulation is also indicated in patients receiving a short-acting fibrinolytic agent (eg, recombinant tissue-type plasminogen activator) and those receiving a glycoprotein IIb/IIIa inhibitor.
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Anticoagulant options include unfractionated heparin (UFH), bivalirudin, low-molecular-weight heparin (LMWH) agents such as enoxaparin and dalteparin, and fondaparinux. LMWH provides more stable anticoagulation than UFH and offers the advantage of subcutaneous administration without the need to monitor activated partial thromboplastin time (aPTT). In addition, LMWHs have been associated with improved clinical outcomes although they are contraindicated in renal failure and have been associated with increased bleeding in older adults, which may be due to decreased creatinine clearance.
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Antiplatelet therapy—
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Antiplatelet agents that block the ADP receptor have been shown to reduce repeat major cardiac events after percutaneous coronary stent implantation in ACS patients. In addition, these agents reduce cardiovascular mortality, nonfatal MI, and nonfatal stroke by approximately 20% compared with aspirin alone during long-term therapy after NSTEMI. Currently available agents include clopidogrel, prasugrel, and ticagrelor. Prasugrel is more potent than clopidogrel but is not recommended in patients older than 75 years because of the bleeding risk. Clopidogrel recently became generic and is the most commonly used ADP receptor antagonist. The initial dosage is 300–600 mg orally followed by 75 mg daily.
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Glycoprotein IIb/IIIa inhibitors—
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These potent antiplatelet agents block the final pathway leading to platelet aggregation. Available agents include abciximab, eptifibatide, and tirofiban. Most data for these agents came prior to the routine use of ADP receptor antagonists, where they were shown to reduce the risk of recurrent ischemic events and improve clinical outcomes in patients with documented MI, particularly those undergoing percutaneous coronary revascularization. These agents similarly benefit younger and older patients, although the risk of bleeding is higher in those who are older; dosage adjustment may be necessary in patients with impaired renal function.
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Early administration of intravenous β blockers reduces mortality partly because of reduced sudden cardiac death, recurrent ischemic events, and both supraventricular and ventricular tachyarrhythmias in appropriately selected ACS patients. Intravenous β-blocker therapy should be initiated as soon as possible in all patients with suspected ACS in the absence of contraindications (ie, heart rate <50 beats/min, systolic BP <90–100 mm Hg, PR interval ≥240 milliseconds, heart block greater than first degree, moderate or severe pulmonary congestion, or active bronchospasm).
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Cardioselective β blockers are preferred, and intravenous metoprolol and atenolol have been approved for treatment of ACS. Patients receiving intravenous β blockers should be carefully observed for bradyarrhythmias, hypotension, dyspnea, and bronchospasm. It is prudent to use lower dosages and a slower dose titration schedule in patients older than 75 years and in those with multiple comorbidities or unstable hemodynamics. Dose adjustment is necessary for atenolol in renal impairment.
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Angiotensin-Converting Enzyme Inhibitors & Angiotensin Receptor Blockers
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Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are beneficial in patients 65–74 years of age, but there is no clear evidence of benefit in patients older than age 75 years. Data suggest that ACE inhibitors are particularly beneficial in patients with anterior STEMIs and MIs complicated by clinical heart failure or significant LV systolic dysfunction (LV ejection fraction <40%). Contraindications to ACE inhibitors include systolic BP <90–100 mm Hg, advanced renal insufficiency—especially if worsening renal function is evident, bilateral renal artery stenosis, and hyperkalemia. ACE inhibitor therapy can be initiated with captopril 6.25 mg 3 times a day or enalapril 2.5 mg twice daily. Once the maintenance dose has been achieved, changing to a once-daily agent at equivalent dosage (eg, lisinopril 20–40 mg) is appropriate. Throughout the initiation and titration phase of ACE inhibitor therapy, BP, serum creatinine, and potassium should be carefully monitored. ARBs are generally used for patients who do not tolerate ACE inhibitors because of cough.
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Lipid-Lowering Agents
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3-Hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitors (statins) should be initiated early in the course of ACS at high doses (eg, atorvastatin 80 mg) and continued indefinitely. These agents have been shown to decrease mortality and recurrent ischemic events after NSTEMI and STEMI.
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Nitrate preparations are effective in controlling ischemia, treating heart failure, and managing hypertension in patients with ACS. As noted above, the options include sublingual nitroglycerin, topical nitroglycerin ointment, and intravenous nitroglycerin infusion. Nitrate tolerance generally occurs within about 24 hours.
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Calcium Channel Blockers
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Calcium channel blockers have not been shown to improve mortality in ACS patients, and the use of short-acting dihydropyridines (eg, nifedipine) is contraindicated, as are the nondihydropyridines (eg, verapamil and diltiazem) in patients with heart failure and LV dysfunction.
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Potassium & Magnesium
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Potassium should be maintained within a range of 3.5–4.5 mEq/L and magnesium above 2.0 mEq/L.
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Approximately 15% to 20% of patients with STEMI die before reaching the hospital, a proportion that likely increases with advancing age. Among patients with recognized ACS, both short- and long-term mortality increase progressively with age. Other factors associated with increased mortality include anterior MI, clinical heart failure, impaired LV systolic function, atrial fibrillation, complex ventricular arrhythmias, poor functional status, diabetes mellitus, and lack of guideline-based treatment. Although short-term prognosis is more favorable in NSTEMI than in STEMI, mortality rates at 2 years are similar.
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