Clinical Pharmacology of Drugs Used to Treat Angina

CLINICAL PHARMACOLOGY OF DRUGS USED TO TREAT ANGINA

Because the most common cause of angina is atherosclerotic dis-ease of the coronaries (CAD), therapy must address the underlying causes of CAD as well as the immediate symptoms of angina. In addition to reducing the need for antianginal therapy, such primary management has been shown to reduce major cardiac events such as myocardial infarction.

First-line therapy of CAD depends on modification of risk fac-tors such as smoking, hypertension , hyperlipi-demia , obesity, and clinical depression. In addition, antiplatelet drugs  are very important.

Specific pharmacologic therapy to prevent myocardial infarction and death consists of antiplatelet agents (aspirin, ADP receptor blockers) and lipid-lowering agents, especially statins. Aggressive therapy with statins has been shown to reduce the incidence and severity of ischemia in patients during exercise testing and the incidence of cardiac events (including infarc-tion and death) in clinical trials. ACE inhibitors also reduce the risk of adverse cardiac events in patients at high risk for CAD, although they have not been consistently shown to exert antianginal effects. In patients with unstable angina and non-ST-segment elevation myo-cardial infarction, aggressive therapy consisting of coronary stenting, antilipid drugs, heparin, and antiplatelet agents is recommended. The treatment of established angina and other manifestations of myocardial ischemia includes the corrective measures previously described as well as treatment to prevent or relieve symptoms. Treatment of symptoms is based on reduction of myocardial oxy-gen demand and increase of coronary blood flow to the potentially ischemic myocardium to restore the balance between myocardial oxygen supply and demand.

Angina of Effort

Many studies have demonstrated that nitrates, calcium channel blockers, and β blockers increase time to onset of angina and ST depression during treadmill tests in patients with angina of effort (Figure 12–5). Although exercise tolerance increases, there is usu-ally no change in the angina threshold, ie, the rate-pressure prod-uct at which symptoms occur.

For maintenance therapy of chronic stable angina, long-acting nitrates, calcium channel-blocking agents, or β blockers may be chosen; the drug of choice depends on the individual patient’s response. In hypertensive patients, monotherapy with either slow-release or long-acting calcium channel blockers or β blockers may be adequate. In normotensive patients, long-acting nitrates may be suitable. The combination of a β blocker with a calcium chan-nel blocker (eg, propranolol with nifedipine) or two different calcium channel blockers (eg, nifedipine and verapamil) has been shown to be more effective than individual drugs used alone. If response to a single drug is inadequate, a drug from a different class should be added to maximize the beneficial reduction of cardiac work while minimizing undesirable effects (Table 12–7). Some patients may require therapy with all three drug groups.

Surgical revascularization (ie, coronary artery bypass grafting [CABG]) and catheter-based revascularization (ie, percutaneous coronary intervention [PCI]) are the primary methods for promptly restoring coronary blood flow and increasing oxygen supply in unstable or medically refractory angina.

Vasospastic Angina

Nitrates and the calcium channel blockers are effective drugs for relieving and preventing ischemic episodes in patients with variant angina. In approximately 70% of patients treated with nitrates plus calcium channel blockers, angina attacks are completely abol-ished; in another 20%, marked reduction of frequency of anginal episodes is observed. Prevention of coronary artery spasm (with or without fixed atherosclerotic coronary artery lesions) is the princi-pal mechanism for this beneficial response. All presently available calcium channel blockers appear to be equally effective, and the choice of a particular drug should depend on the patient. Surgical revascularization and angioplasty are not indicated in patients with variant angina.

Unstable Angina & Acute Coronary Syndromes

In patients with unstable angina with recurrent ischemic episodes at rest, recurrent platelet-rich nonocclusive thrombus formation is the principal mechanism. Aggressive antiplatelet therapy with a combination of aspirin and clopidogrel is indicated. Intravenous heparin or subcutaneous low-molecular-weight heparin is also indicated in most patients. If percutaneous coronary intervention with stenting is required, glycoprotein IIb/IIIa inhibitors such as abciximab should be added. In addition, therapy with nitroglyc-erin and β blockers should be considered; calcium channel block-ers should be added in refractory cases for relief of myocardialischemia. Primary lipid-lowering and ACE-inhibitor therapy should also be initiated.