The role of calcium antagonists in ischaemic heart disease.
Calcium antagonists are well accepted in the prevention of ischaemia in patients with chronic stable angina, unstable angina, variant angina, and silent ischaemia, and in the treatment of hypertension. Although all of these compounds increase myocardial oxygen supply by reducing coronary tone and decrease myocardial oxygen demand by reducing systolic pressure and myocardial contractility, the magnitude of these effects may differ from one agent to another. Some calcium antagonists, such as verapamil and diltiazem, reduce heart rate and attenuate heart rate increases in response to stress, while in contrast, dihydropyridine calcium antagonists such as nifedipine may cause reflex increases in heart rate. These differences may be of importance in light of epidemiologic evidence that lower heart rates are associated with a reduced long-term risk of cardiovascular mortality, and experimental data showing that a lower heart rate may protect against the development of atherosclerosis. Calcium antagonists also inhibit platelet aggregation and thrombus formation which may contribute to their anti-ischaemic effects. Clinical trial data suggest that calcium antagonists may stay the progression of atherosclerosis. Mechanisms underlying an anti-atherosclerotic effect may include attenuation of endothelial dysfunction, prevention of LDL, peroxidation, stimulation of LDL receptor activity, inhibition of superoxide radical generation, and inhibition of vascular smooth muscle cell growth. Heart-rate-controlling calcium antagonists, such as verapamil and diltiazem, may reduce reinfarction rates following acute myocardial infarction and thus may have a role in post-infarction patients who do not show evidence of heart failure. Their use in heart failure patients receiving an angiotension-converting enzyme inhibitor (ACE-I) is under investigation in several large trials. Because calcium antagonists have a mechanism of action different from ACE-I, the pairing of a heart-rate-controlling calcium antagonist with an ACE-I might be expected to offer additive cardioprotective and vascular protective effects.
Pepine
C J
CJ
Division of Cardiology, University of Florida, Gainesville, USA.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D004095:Dihydropyridines / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects; D005609:Free Radicals; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D005609:Free Radicals; D008077:Lipoproteins, LDL; D010975:Platelet Aggregation Inhibitors; D013481:Superoxides