The combination of antianginal drugs: effects and indications.

Today, three classes of drugs, all acting differently on the myocardium, the coronary circulation, and the peripheral circulation, that is, on the determinants for myocardial oxygen consumption (heart rate, contractility, and wall tension), are at the physician's disposition for anti-ischemic medical treatment: nitrates, beta-receptor blocking agents and Ca antagonists. All three drugs have been proven to exhibit a marked antianginal effect when given alone, as demonstrated both by an improvement in exercise performance as well as in perfusion and a significant decrease in symptomatic and silent ischemic episodes. Treatment should cover the total ischemic burden, which can be assessed today more accurately by Holter monitoring than with exercise tests alone. It has been shown in patients with stable angina that the majority of ischemic episodes are silent (over 75%); therefore, the question arose as to whether medical anti-ischemic treatment should aim at the prevention not only of symptomatic, but also of silent episodes. Furthermore, ischemia was revealed to be not only a marker for the presence of high-grade life-threatening obstructions, but also to have prognostic implications, not only in symptomatic, but also in asymptomatic episodes. In addition, ischemia can lead to life-threatening arrhythmia and irreversible myocardial damage, especially localized fibrosis. To what extent this is prevented by vigorous anti-ischemic treatment is still unanswered; however, as pathophysiologically symptomatic and asymptomatic ischemic episodes behave similarly, the latter should be included in treatment. The combinations of drugs, especially of nitrates and beta blockers, Ca antagonists and beta blockers, and also nitrates and Ca antagonists result in a further improvement in exercise performance and a reduction in ischemic episodes, allow the dose to be reduced, and minimize side effects. In addition, as is indicated from their hemodynamics, in special clinical situations, combinations might be preferable. Whether treatment should primarily reduce sympathetic drive or, rather, be directed towards vasodilation depends on the type of angina and the individual need. Hence, combining drugs in treating angina pectoris represents a true therapeutic challenge for the physician.