EFFECTS OF AMLODIPINE VERSUS DILTIAZEM ON MORNING PEAK IN MYOCARDIAL ISCHEMIC ACTIVITY IN ANGINA-PECTORIS

Many studies have confirmed a peak in the onset of acute myocardial infarction, sudden cardiac death and ischemic activity in the morning waking hours in patients with coronary artery disease. Factors potentially relevant to this observed surge in activity include marked increases in heart rate, blood pressure, catecholamine release, coronary artery tone and platelet aggregability, and a trough in the fibrinolytic state at this time. 1 Various studies have shown that β-adrenergic blockade is effective in blunting particularly the morning surge in ischemic activity,2,3 onset of acute myocardial infarction, 4 and sudden cardiac death5; however, despite the powerful coronary vasodilating and afterload-reducing properties of calcium antagonists, they have not been shown to alter the morning surge in ischemia2,6 (except in high doses7), or the morning peak in onset of myocardial infarction.4 Although the recently published nifedipine Gastrointestinal Therapeutic System (GITS) study showed an overall modification of the circadian pattern of ischemia with nifedipine GITS as monotherapy, there appeared to be no difference in circadian patterns during such active therapy and subsequent placebo withdrawal.8 It is possible that previous studies of calcium antagonists without either a 24-hour profile or chronotropic control have resulted in (1) the morning waking period being "unprotected" regarding efficacious plasma levels of drug on waking, and/or (2) an absence of modification of the heart rate response to increasing and commencing activity, a mechanism by which β blockers may, at least partially, exert their effects. © 1993.