Efficacy and safety of calcium channel blockers in heart failure: Focus on recent trials with second-generation dihydropyridines

Background Chronic heart failure (CHF) has high morbidity and mortality rates despite treatment with angiotensin-converting enzyme inhibitors, diuretics, and digoxin. Adjunctive vasodilation through calcium channel blockade has been suggested as potentially useful. However, the first-generation calcium channel blockers, including the dihydropyridine nifedipine, showed disappointing results in CHF. The second-generation dihydropyridines were expected to be of more value, and of all the calcium channel blockers, these drugs were the ones most studied in patients with CHF. Methods and Results The Medline databank was used to search studies in human beings (published in 1990 or later) that used dihydropyridines in patients with CHF. The references of the studies found were subsequently checked for additional data. In 17 studies and more than 2000 patients with CHF, no consistent beneficial effect was observed with regard to exercise tolerance and functional capacity, whereas plasma neurohormones were not affected. On the other hand, in general, no worsening of CHF was seen with these second-generation dihydropyridines. Two larger studies (PRAISE and V-HeFT III) have given some estimates on the long-term effects of dihydropyridines, and no overall influence on mortality rate was found. Of note, subanalysis of the PRAISE study has suggested that in patients with a nonischemic cause of CHF, amlodipine might have a beneficial effect on survival. Conclusions In this review we have focused on the efficacy and safety of dihydropyridines in patients with CHF, as reported in recent trials. The data do not support the use of dihydropyridines when primarily given as treatment for CHF. The results, however, suggest that these drugs can be safely given to patients with left ventricular dysfunction or CHF who need additional treatment for angina pectoris or hypertension.