It is useful to classify therapeutic drugs into two categories: antianginal (anti-ischemic) agents and vasculoprotective agents. Although medications for angina are widely used, therapy to slow the progression of coronary artery disease, to induce the stabilization of plaque, or to do both is a newer concept and these forms of treatment are underprescribed.
All antianginal drugs - nitrates, beta-adrenergic blockers, and calcium-channel blockers - have been shown to prolong the duration of exercise before the onset of angina and ST-segment depression as well as to decrease the frequency of angina. Treadmill performance typically increases by 30 to 60 seconds with antianginal drugs as compared with performance with placebo. However, none of these agents have been shown to prevent myocardial infarction or death from coronary disease in patients being treated specifically for chronic stable angina.
Head-to-head comparative trials have not demonstrated that any single class of drugs has greater antianginal efficacy than the others. Thus, it is reasonable to begin therapy with agents from any of the three groups.
Beta-blockers work primarily by decreasing myocardial oxygen consumption through reductions in heart rate, blood pressure, and myocardial contractility. Although beta-blockers have not been shown to reduce the rate of coronary events or mortality specifically in patients with chronic stable angina, they are identified as class I drugs (i.e., there is evidence or general agreement that they are useful and effective), according to the 2002 American College of Cardiology-American Heart Association guidelines for the management of stable angina. This classification is based on older trials showing that these agents prolong survival after myocardial infarction and on recent data showing that they have a similar benefit after primary angioplasty for acute non-ST-elevation myocardial infarction. There have been no large trials assessing the effects of beta-blockers on survival or on rates of coronary events in patients with chronic stable angina. The side effects associated with beta-blockers are often overemphasized; these drugs can be used effectively in many patients with Chronic obstructive pulmonary disease or peripheral Peripheral vascular disease.
Calcium antagonists dilate coronary and systemic arteries, increase coronary blood flow, and decrease myocardial oxygen consumption. Although the safety of long-acting calcium-channel blockers has been questioned, data from ALLHAT (the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart attacks Trial) and the results of a recent meta-analysis by the Blood Pressure Lowering Treatment Trialists’ Collaboration indicate that the use of these drugs for hypertension does not increase morbidity or mortality.
Nitrates dilate systemic and coronary arteries, including some coronary stenoses, and particularly the systemic veins; venous pooling of blood decreases cardiac work and chamber size. Sublingual or oral spray nitroglycerin relieves acute episodes of angina within 5 to 10 minutes; prophylactic use before activity can be helpful in persons with frequent angina. Whereas long-acting nitrates decrease angina and prolong exercise performance, experimental data and data from catheterization laboratories suggest that nitrates increase vascular oxidative stress and may induce paradoxical coronary arterial vasoconstriction. Both appear to contribute to the development of nitrate tolerance. Prevention of tolerance requires an intermittent dosing strategy, with a nitrate-free interval of 12 to 14 hours. Phosphodiesterase type 5 inhibitors (e.g., sildenafil, vardenafil, and tadalafil) and nitrates should not be used within 24 hours of one another because of the potential for serious hypotension.
Underdosing with antianginal agents is common. Even when the dosage is appropriate, physicians should anticipate the need for treatment with two or three agents in many patients. Certain drug combinations are recommended, and others should be avoided because of potential hypotension or bradycardia. Data from randomized clinical trials support the efficacy of combined therapy with two drugs but provide less support for the use of three agents together.
There is considerable evidence that lifestyle changes and pharmacologic therapy may reduce the progression of Atherosclerosis, stabilize plaque, or both in chronic stable angina. Aggressive interventions are warranted to control all cardiovascular risk factors, including Diabetes and hypertension (a target blood pressure of < 130/80 mm Hg is appropriate for both conditions) in persons with coronary artery disease.
Revision date: June 20, 2011
Last revised: by Jorge P. Ribeiro, MD