Angina Pectoris

Angina pectoris is the result of myocardial ischemia caused by an imbalance between myocardial blood supply and oxygen demand. Angina is a common presenting symptom (typically, chest pain) among patients with coronary artery disease.

Causes
Decrease in myocardial blood supply due to increased coronary resistance in large and small coronary arteries Significant coronary atherosclerotic lesion in the large epicardial coronary arteries (ie, conductive vessels) with at least a 50% reduction in arterial diameter Coronary spasm (ie, Prinzmetal angina) Abnormal constriction or deficient endothelial-dependent relaxation of resistant vessels associated with diffuse vascular disease (ie, microvascular angina) Syndrome X Systemic inflammatory or collagen vascular disease, such as scleroderma, systemic lupus erythematous, Kawasaki disease, polyarteritis nodosa, and Takayasu arteritis Increased extravascular forces, such as severe LV hypertrophy caused by hypertension, aortic stenosis, or hypertrophic cardiomyopathy, or increased LV diastolic pressures Reduction in the oxygen-carrying capacity of blood, such as elevated carboxyhemoglobin or severe anemia (hemoglobin, < 8 g/dL) Congenital anomalies of the origin and/or course of the major epicardial coronary arteries Structural abnormalities of the coronary arteries Congenital coronary artery aneurysm or fistula Coronary artery ectasia Coronary artery fibrosis after chest radiation Coronary intimal fibrosis following cardiac transplantation Risk factors Major risk factors for atherosclerosis: These include a family history of premature coronary artery disease, cigarette smoking, diabetes mellitus, hypercholesterolemia, or systemic hypertension. Other risk factors: These include LV hypertrophy, obesity, and elevated serum levels of homocysteine, lipoprotein (a), plasminogen activator inhibitor, fibrinogen, serum triglycerides, or low high-density lipoprotein (HDL). Metabolic syndrome: This has been characterized by the presence of hyperinsulinemia (fasting glucose level, 100 mg/dL), abdominal obesity (waist circumference, >40 in for men or >35 in for women), decreased HDL cholesterol levels (< 40 mg/dL for men or < 50 mg/dL for women), hypertriglyceridemia (>150 mg/dL), and hypertension ( 130/85 mm Hg). Based on data from the 2000 US census, an estimated 47 million Americans have the metabolic syndrome. Patients with the metabolic syndrome have a 3-fold increased risk for coronary atherosclerosis and stroke compared with those without this syndrome.[7] Precipitating factors: These include factors such as severe anemia, fever, tachyarrhythmias, catecholamines, emotional stress, and hyperthyroidism, which increase myocardial oxygen demand. Preventive factors: Factors associated with reduced risk of atherosclerosis are a high serum HDL cholesterol level, physical activity, estrogen, and moderate alcohol intake (1-2 drinks/d). Medication Summary The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Antiplatelet agents Class Summary Prevent thrombus formation by inhibiting platelet aggregation. Aspirin is proven beneficial in primary and secondary prevention of coronary artery disease. In patients with aspirin intolerance, use clopidogrel. Clopidogrel is also used in combination with aspirin after coronary stent placement. Recently, clopidogrel use in addition to aspirin has been shown to be significantly superior to aspirin alone in patients with acute coronary syndrome without ST-segment elevation MI. View full drug information Aspirin (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin)

Prevents platelet aggregation by irreversible cyclooxygenase inhibition with subsequent suppression of thromboxane A2. Antiplatelet effect can last as long as 7 d. Clopidogrel (Plavix)

Selectively inhibits ADP binding to platelet receptor and subsequent ADP-mediated activation of GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Consider in patients with contraindication to aspirin. Beta-adrenergic blocking agents Class Summary Work by competing with endogenous catecholamines for beta-adrenergic receptors. Reduce myocardial oxygen consumption via several effects, including decrease in resting and exercise heart rates and reductions in myocardial contractility and afterload. Classified as nonselective, beta-1 selective, and having intrinsic sympathomimetic effects. Metoprolol (Lopressor, Toprol XL)

Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. Is lipophilic and penetrates CNS. Atenolol (Tenormin)

Selectively blocks beta-1 receptors with little or no effect on beta-2 receptors. Is hydrophilic and does not penetrate CNS. View full drug information Propranolol (Inderal)

Nonselective beta-blocker that is lipophilic (penetrates CNS). Although generally short-acting agent, long-acting preparations also available. Calcium channel blockers Class Summary Reduce transmembrane flux of calcium via calcium channels. Cause smooth muscle relaxation, resulting in peripheral arterial vasodilation and afterload reduction. Indicated when symptoms persist despite

treatment with beta-blockers or when beta-blockers are contraindicated. Also indicated in patients with Prinzmetal angina with or without nitrates. Amlodipine (Norvasc)

During depolarization, inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium. Diltiazem (Cardizem CD, Dilacor)

During depolarization, inhibits calcium ions from entering slow channels and voltage-sensitive areas of Verapamil (Calan, Covera)

During depolarization, inhibits calcium ion from entering slow channels or voltage-sensitive areas of vascular smooth muscle and myocardium. Short-acting nitroglycerins Class Summary Suitable for immediate relief of exertional or rest angina. Can also be used for prophylaxis several minutes before planned exercise to avoid angina. Reduce myocardial oxygen demand by reduction of LV and arterial pressure, primarily by reducing preload. Nitroglycerin IV (Nitrostat, Nitro-bid, Nitrol)

Causes relaxation of vascular smooth muscle by stimulating intracellular cyclic GMP production. Result is decrease in BP. Long-acting nitroglycerins Class Summary Reduce LV preload and afterload by venous and arterial dilation, which subsequently reduces myocardial oxygen consumption and relieves angina. Also cause dilation of epicardial coronary arteries, which is beneficial in patients with coronary spasm. In addition, nitroglycerin has antithrombotic and antiplatelet effects in patients with angina pectoris. No evidence suggests that nitrates improve survival or slow progression of coronary artery disease. View full drug information Isosorbide (Isordil, ISMO)

Relaxes vascular smooth muscle by stimulating intracellular cyclic GMP. Decreases LV pressure (ie, preload) and arterial resistance (ie, afterload). Reduces cardiac oxygen demand by decreasing LV pressure and dilating arteries. Angiotensin-converting enzyme inhibitors Class Summary Angiotensin-converting enzyme (ACE) Inhibitors have been shown to reduce rates of death, MI, stroke, and need for revascularization procedures in patients with coronary artery disease or diabetes mellitus

and at least one[44] other cardiovascular risk factor, irrespective of the presence of hypertension or heart failure. The 2009 Canadian Hypertension Education Program recommends beta-blockers and ACE inhibitors as first-line therapy that patients with angina, recent myocardial infarction or heart failure.[45] Ramipril (Altace)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion. Anti-ischemic agents, miscellaneous Class Summary Ranolazine elicits action unlike beta-blockers, calcium antagonists, or nitrates. It does not affect hemodynamics or contractile and conduction parameters. View full drug information Ranolazine (Ranexa)

Cardioselective anti-ischemic agent (piperazine derivative) that partially inhibits fatty acid oxidation. Also inhibits late sodium current into myocardial cells and prolongs QTc interval. Indicated for chronic angina unresponsive to other antianginal treatments. Used in combination with amlodipine, betablockers, or nitrates. Unlike beta-blockers, calcium channel blockers, and nitrates, does not reduce blood pressure or heart rate. Effect on angina rate or exercise tolerance appears to be smaller in women than in men. Absorption is highly variable but unaffected by food.