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Pathophysiological mechanisms underlying the adverse effects of calcium channel-blocking drugs in patients with
1Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
Insights
Calcium channel blockers do not benefit chronic heart failure patients and may increase risks. Their long-term harm is linked to activating neurohormonal systems, unlike beneficial beta-blockers and ACE inhibitors.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Calcium channel blockers (CCBs) are expected to aid chronic heart failure (CHF) due to vasodilation.
- However, CCBs have shown no clinical benefit and can increase morbidity/mortality in CHF patients with impaired left ventricular function.
Purpose of the Study:
- To investigate the mechanisms behind the adverse effects of CCBs in chronic heart failure.
- To differentiate the effects of CCBs from other cardioactive drugs like beta-blockers and ACE inhibitors.
Main Methods:
- The study reviews existing research on CCBs, beta-blockers, and ACE inhibitors in heart failure.
- It hypothesizes mechanisms based on drug effects on cardiac contractility and neurohormonal systems.
Main Results:
- Negative inotropic effects of CCBs explain short-term harm.
- Long-term harm is attributed to CCB activation of neurohormonal systems, particularly the renin-angiotensin system.
- Beta-blockers and ACE inhibitors, which inhibit neurohormonal systems, show favorable outcomes.
Conclusions:
- CCBs adversely affect patients with left ventricular dysfunction by activating neurohormonal systems.
- Beta-blockers and ACE inhibitors offer long-term benefits by interfering with these systems.
- Drug effects on both contractility and neurohormonal systems are crucial for selecting antianginal agents in coronary artery disease and heart failure.
Abstract:
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.