CALCIUM-CHANNEL BLOCKERS IN HEART-FAILURE

A considerable effort has been made in the last 15 years to evaluate t he safety and efficacy of calcium channel blockers (CCBs) in the treat ment of patients with chronic congestive heart failure (CHF). Availabl e studies have provided strong evidence for a potential detrimental ef fect of the first-generation calcium antagonists in patients with CHF, indicating the need for great caution when these drugs are used in pa tients with significant depression of left ventricular systolic functi on. A number of second-generation CCB have demonstrated a strong vasod ilatory effect and favorable hemodynamic action but failed to show a s imilar improvement in exercise capacity, morbidity and mortality. More over, drugs such as nicardipine and nisoldipine have resulted in a det rimental effect in some patients and, therefore, cannot be considered safe when used in patients with moderate-to-severe heart failure. Avai lable information from the V-HeFT III study demonstrate a lack of an u nfavorable effect of felodipine on exercise tolerance in patients with chronic heart failure. Although mortality rate was similar in both th e felodipine and the placebo group, because of the relatively small nu mber of patients in this study, no clear conclusion can be drawn regar ding the effect of felodipine on mortality in patients with CHF. An en couraging signal regarding a potential role of CCB in the treatment of chronic heart failure has been provided by the recently completed PRA ISE 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. Furthermor e, this study demonstrated a substantial reduction in mortality in pat ients with CHF due to nonischemic cardiomyopathy and provided a strong indication for a potential therapeutic benefit of amlodipine when add ed to standard CHF therapy in this patient population. No clear explan ation is available at the present time regarding the reason for the de leterious effect demonstrated with some of the dihydropyridines and th e contrasting benefit seen with amlodipine. Finally, more information regarding the safety and efficacy of dihydropyridines should become av ailable in the next year. The PRAISE II study is ongoing and will prov ide further information regarding the therapeutic role of amlodipine i n patients with nonischemic dilated cardiomyopathy. The MACH-1 study i s evaluating the effect of mibefradil, a predominant T-type channel bl ocker with an ideal activity profile, on morbidity and mortality in pa tients with chronic CHF.