Pathophysiological mechanisms underlying the adverse effects of calcium channel-blocking drugs in patients with chronic heart failure.
Although the vasodilator and anti-ischemic actions of calcium channel blocking drugs might be expected to produce hemodynamic benefits in chronic heart failure, none of these agents has been shown to exert favorable clinical effects in these patients. Furthermore, when left ventricular function is markedly impaired, short- and long-term therapy with calcium channel blockers can increase cardiovascular morbidity and mortality. Previous investigators have attributed these unfavorable results to the established negative inotropic effects of calcium channel blockers on the failing heart. Yet, this cardiodepressant action seems to account for only the deleterious responses seen during short-term therapy with these drugs, whereas the detrimental effects of long-term treatment can be more readily explained by the capacity of calcium channel blockers to activate endogenous neurohormonal systems, especially the renin-angiotensin system. According to this hypothesis, a number of cardioactive drugs (including calcium channel blockers, beta-blockers, and converting enzyme inhibitors) can depress myocardial contractility, but only calcium channel blockers, which activate neurohormonal systems, adversely affect patients with left ventricular dysfunction, whereas beta-blockers and converting enzyme inhibitors, which interfere with neurohormonal activity, can favorably modify the long-term outcome of these high-risk patients. If confirmed by future studies, these observations suggest that the effect of antianginal drugs on neurohormonal systems, as well as on cardiac contractility, should be an important consideration in the selection of a therapeutic agent in patients with coronary artery disease and chronic heart failure.
Packer
M
M
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
D002121:Calcium Channel Blockers / Q000009:adverse effects* / Q000627:therapeutic use; D003864:Depression, Chemical; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects; D009490:Neurosecretory Systems / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects; D013997:Time Factors
D002121:Calcium Channel Blockers