MEDICAL MANAGEMENT OF ANGINA



Angina is treated by decreasing myocardial ox­ygen demand or increasing oxygen supply. Cer­tain general measures may be helpful. Avoiding situations that may increase oxygen demand (for example, cold weather, particularly large meals,and excessive exercise) may be effective. Control of hypertension and correction of other exacer­bating conditions such as anemia, infection, hy­poxia, and thyrotoxicosis is necessary. Cigarette smoking should be stopped. Treatment of conges­tive heart failure decreases oxygen consumption and improves oxygen delivery. After physical training under supervised programs the patient may be able to perform tasks with a lower heart rate-blood pressure product and less angina. Whether exercise increases collateral circulation and oxygen delivery is controversial.

The most time-honored antianginal medication is nitroglycerin (Table 7-3), a smooth muscle re­laxant of both systemic arteries and veins, al­though it affects veins predominantly. A decrease in venous return to the heart decreases preload, decreases left ventricular volume, and subse­quently reduces wall tension and afterload. These hemodynamic effects are also of value in treating congestive heart failure. In addition, nitroglycerin dilates the larger conductance coronary arteries and probably also the collateral vessels, thus di­rectly increasing blood supply to ischemic myo­cardium. The reduction in ventricular diastolic pressure brought about by nitrates may lower re­sistance to coronary blood flow within the myo­cardium during diastole.

Beta-adrenergic receptor blockade slows the resting heart rate, blunts the increase in heart rate with exercise, and decreases myocardial contractility, all of which decrease ox­ygen consumption. In addition, beta-blocking drugs are useful antihypertensive agents and may reduce cardiac afterload in such patients. Beta-adrenergic receptors can be divided into beta-1 and beta-2 subgroups. The beta-1 receptors me­diate the cardiac actions of the sympathetic ner­vous system, whereas beta-2 receptors promote the glycogenolysis induced by catecholamines, vasodilation of peripheral blood vessels, and di­lation of pulmonary bronchi. Therefore, beta blockers that have predominantly beta-1 rather than beta-2 sympathetic antagonism (e.g., atenolol and metoprolol) may be more useful in treating patients with bronchospastic pulmonary disease, chronic obstructive pulmonary disease, diabetes, and peripheral vascular disease. However, selec­tive beta-1 blockade is only relative, and at higher doses (for example, above 100 mg a day of me­toprolol) the selectivity may be lost.- Hydrophilic beta blockers, for example atenolol and nadolol, have relatively long half-lives, can be adminis­tered once daily, and tend not to penetrate into the central nervous system, which may produce fewer neurological side effects such as mental depression and sleep disturbances. Thus, side ef­fects attributed to one beta blocker may be elim­inated by switching to another. Pindolol has mild intrinsic sympathomimetic activity in addition to its beta receptor-blocking activity; that is, it acts as a beta receptor agonist as well as antagonist. Theoretically, some of the effects at rest of beta-receptor blockade such as slow heart rate or pe­ripheral vasoconstriction may be less prominent even though the sympathetic effects of exercise are blocked. Any clinical advantage to beta-re­ceptor blockers with intrinsic sympathomimetic activity is not clear at present.

Calcium ions play critical roles in myocardial contraction, coronary vascular smooth muscle constriction, and the genesis of the cardiac action .potential. Slow channel blocking agents are ef­fective antianginal drugs when used either alone or in combination with beta-receptor adrenergic blockers or nitrates (Table 7-6). All three agents currently available in the United States (nifedi­pine, verapamil, and diltiazem) decrease myocar­dial contractility and relax coronary and periph­eral vascular smooth muscle. Verapamil and diltiazem may decrease the sinus nodal discharge rate and prolong atrioventricular (AV) nodal con­duction time. In clinically used doses, nifedipine is the most potent vasodilator of the three and ex­erts little action on myocardial contractility or on the sinus and AV nodes. Therefore, nifedipine de­creases afterload via peripheral vasodilation and increases coronary blood flow via coronary va­sodilation. The antianginal effect of verapamil may be related to both coronary artery vasodila­tion and decreased myocardial contractility, thus decreasing oxygen demand. The effects on con­tractility and sinus rate are minimized owing to reflex sympathetic stimulation in response to the peripheral vasodilation. Verapamil and the other calcium antagonists enhance left ventricular dias­tolic filling (increase compliance); this is not an effect of simple beta blockade. In general, the ef­fects of diltiazem are intermediate between those of verapamil and nifedipine.

Since the mechanisms of action of nitrates, beta-receptor blockers, and calcium antagonists differ, combination therapy of two or three of these drugs might be effective. Nitrates can cause reflex tachycardia that beta-receptor blockers can prevent. Therefore, in a patient with no contrain­dication to beta-receptor blockade, the combina­tion of nitrates and a beta-receptor blocker may be beneficial antianginal therapy. In addition, the combination of beta blockers and calcium channel blockers is often useful if unwanted electrophy­siological or inotropic side effects do not become manifest. Especially useful combinations may be a beta-receptor blocker plus nifedipine, or vera­pamil and a long-acting nitrate; these combina­tions would provide - coronary arterial dilation along with decreased myocardial contractility and oxygen demand without subjecting the pa­tient to two medications having similar side ef­fects. Patients with particularly severe angina may require one drug from each of the three classes.
A patient experiencing a marked increase in the frequency or severity of angina, the new onset of angina at rest, or nocturnal angina should prob­ably be admitted to an intensive care unit, placed at bed rest, and sedated if necessary. If not con-traindicated, beta blockade should be instituted. Sublingual nitroglycerin, oral and/or cutaneous nitrates should be administered, and if pain re­curs, intravenous nitroglycerin can be initiated. In addition, nifedipine may be useful in the pa­tient with no hypotension or with congestive heart failure. Verapamil or diltiazem may be use­ful in the patient with no heart failure. Most pa­tients having unstable angina experience relief of chest pain with this approach and further evaluation, probably including coronary arteriog­raphy, can be undertaken when the patient is sta­ble and pain-free. If angina does not abate with aggressive medical therapy, the patient should be considered for early coronary arteriography and for angioplasty or bypass surgery. An intra-aortic balloon pump may be inserted before cardiac catheterization or surgery to improve diastolic filling of the coronary arteries and to decrease af-terload. Many patients experience pain relief once balloon counterpulsation is initiated despite re­fractoriness to intensive medical antianginal ther­apy.