THE ROLE OF DILTIAZEM IN TREATING HYPERTENSION AND CORONARY-ARTERY DISEASE - NEW APPROACHES TO PREVENTING FIRST EVENTS

OBJECTIVE: To review the role of diltiazem in treating and preventing a group of cardiovascular diseases, including painful and silent cardi ac ischemia, stroke, nonfatal myocardial infarction and sudden cardiac death, by modulating certain physiological causes that they appear to share. DATA SOURCES: A MEDLINE search was conducted for all clinical articles on the use of diltiazem for hypertension and coronary artery disease. When clinical data were not available, basic research finding s were reviewed. DATA EXTRACTION AND SYNTHESIS: Because many cardiovas cular events show a marked daily periodicity - which appears to coinci de with circadian peaks in the ability of platelets to aggregate, symp athetic activity, coronary tone, blood pressure, heart rare and hemato crit, and a trough in fibrinolytic activity the impact of diltiazem on these physiological changes was assessed. CONCLUSIONS: Diltiazem infl uences many of these events by increasing myocardial bloodflow, and re ducing myocardial oxygen demand and cardiac workload. However, it diff ers from other calcium antagonists in its mild negative inotropic and moderate negative dromotropic effects, without apparent stimulation of cardiac performance or contractility. In addition, it inhibits platel et aggregation, decreases catecholamine release, diminishes coronary t one and blocks the vasoconstrictive actions of endothelin-1. This appe ars to translate into a beneficial effect on ischemia, thrombolysis, a rrhythmias, infarct parameters, atherosclerosis and hypertension. Dilt iazem has a relatively favourable safety and tolerability profile, and is available in a once-dairy dosage form. The most common adverse eff ects are related to vasodilation (eg, edema and headache), and the mos t frequent serious adverse event is atrioventricular block, which occu rs rarely. In summary, diltiazem appears to be well suited to preventi ng the first occurrence of cardiovascular events and may even have a r ole in preventing certain types of secondary events. The data accumula ted so far indicate the need for a large scale random clinical trial a ddressing these outcomes.