Nitrates in the Prophylactic Treatment of Angina Pectoris

IT GENERALLY is recognized that prophylactically administered sublingual nitroglycerine exerts a potent yet short-lived beneficial effect on the exercise capacity of patients with coronary artery disease and angina pectoris. Efforts to achieve more prolonged therapeutic action have resulted in the introduction of a variety of nitrate preparations, some with altered molecular structure, others with altered route of administration, still others with both of these changes. Rather than providing a clear solution to a therapeutic problem, however, these preparations have posed a methodologic dilemma: how does one definitely evaluate longacting agents given prophylactically for angina? Measuring blood levels of nitrate esters or assessing the influence of nitrates on circulatory function will certainly contribute much to our understanding of nitrate effects. Nevertheless, the worth of an agent given primarily for the prevention of angina must ultimately rest upon data relating directly to the precipitation of ischemic chest pain. A drug that maintains suitable blood levels, hemodynamic alterations, or even improved ischemic electrocardiographic patterns for prolonged periods would still have only questionable value in the treatment of exertional angina if a concomitant increase in the patient's ability to perform exercise could not be demonstrated. Experience in our laboratory and elsewhere has shown that, when testing conditions are suitable. individuals consistently develop ischemic chest pain after a given duration of exercise, even when multiple exercise trials are performed.' Measuring exercise capacity and the effects of a therapeutic intervention acutely in this manner avoids the variability that fluctuations in daily activity produce when efficacy of a therapeutic intervention is assessed by counting anginal episodes or recording the consumption of nitroglycerin tablets. However, exercise testing may not be as useful in identifying modes of therapy for angina precipitated by factors unrelated to exertion. For example, interventions,