Calcium channel blockers in heart failure

A considerable effort has been made in the last 15 years to evaluate the safety and efficacy of calcium channel blockers (CCBs) in the treatment of patients with chronic congestive heart failure (CHF). Available studies have provided strong evidence for a potential detrimental effect of the first-generation calcium antagonists in patients with CHF, indicating the need for great caution when these drugs are used in patients with significant depression of left ventricular systolic function. A number of second-generation CCB have demonstrated a strong vasodilatory effect and favorable hemodynamic action but failed to show a similar improvement in exercise capacity, morbidity and mortality. Moreover, drugs such as nicardipine and nisoldipine have resulted in a detrimental effect in some patients and, therefore, cannot be considered safe when used in patients with moderate-to-severe heart failure. Available information from the V-HeFT III study demonstrate a lack of an unfavorable effect of felodipine on exercise tolerance in patients with chronic heart failure. Although mortality rate was similar in both the felodipine and the placebo group, because of the relatively small number of patients in this study, no clear conclusion can be drawn regarding the effect of felodipine on mortality in patients with CHF. An encouraging signal regarding a potential role of CCB in the treatment of chronic heart failure has been provided by the recently completed PRAISE study. This prospective large-scale study demonstrated the safety of amlodipine, a long-acting dihydropyridine derivative, when used in patients with heart failure due to coronary artery disease. Furthermore, this study demonstrated a substantial reduction in mortality in patients with CHF due to nonischemic cardiomyopathy and provided a strong indication for a potential therapeutic benefit of amlodipine when added to standard CHF therapy in this patient population. No clear explanation is available at the present time regarding the reason for the deleterious effect demonstrated with some of the dihydropyridines and the contrasting benefit seen with amlodipine. Finally, more information regarding the safety and efficacy of dihydropyridines should become available in the next year. The PRAISE II study is ongoing and will provide further information regarding the therapeutic role of amlodipine in patients with nonischemic dilated cardiomyopathy. The MACH-1 study is evaluating the effect of mibefradil, a predominant T-type channel blocker with an ideal activity profile, on morbidity and mortality in patients with chronic CHF.