The role of transdermal nitroglycerin in the treatment of coronary heart disease.

Nitroglycerin has long been a mainstay of the treatment of ischemic cardiac pain. The introduction of transdermal formulations and in particular the development of controlled methods of delivery have been responsible for the renaissance of clinical interest in this simple and effective treatment. The pathophysiologic abnormality accompanying myocardial ischemia affords a natural theater for the exhibition of the therapeutic utility of these preparations and methods. The means whereby nitrates induce relaxation of vascular smooth muscle are not entirely clear, but their pharmacodynamic activities are perfectly plain. In the doses used in clinical practice, nitrates exert their predominant hemodynamic effects and therapeutic benefits through their peripheral vasodilator activities. This is particularly marked in veins, although in higher doses nitrates also dilate the larger systemic and coronary arteries. Criticisms of the efficacy of transdermal formulations of nitrates in the treatment of angina pectoris have arisen largely from uncritical acceptance of a small number of studies of questionable methodologic validity. Large-scale general practice studies have invariably found that transdermal nitrate delivery systems improve the quality of life in ambulant patients: anginal attacks are reduced with a minimum of side effects. The widespread acceptance of this novel form of drug delivery has stimulated its application in other therapeutic avenues. The efficacy of transdermal nitroglycerin in the suppression of silent ischemic attacks has been demonstrated. The maintenance of benefit initiated by intravenous nitroglycerin in patients with unstable angina also broadens the use of this method of nitrate delivery. In patients with acute myocardial infarction, whether complicated by left ventricular failure or not, the nitrates, and transdermal nitroglycerin in particular, appear to hold considerable promise. Improvement of hemodynamic abnormalities may cause reduction in infarct size and fewer life-threatening arrhythmias. Even survival may be extended. The utility of transdermal nitrates in the treatment of severe chronic heart failure is less certain. But the use of higher doses and an interval regimen of administration may hold promise for such patients. Naturally, more information is required before the overall therapeutic profile of this new method of controlled nitroglycerin delivery across the whole spectrum of coronary heart disease can be fully described. Fortunately, the high level of efficacy and safety of transdermal nitroglycerin demonstrated in the majority of reported studies encourages the pursuit of such an important therapeutic target.