Effects of calcium channel blockers in patients with heart failure with preserved and mildly reduced ejection fraction: A systematic review and meta-analysis

In contrast to beta-blockers and renin-angiotensin system inhibitors, the role of calcium channel blockers (CCBs) in patients with heart failure with preserved ejection fraction (HFpEF) remains uncertain. Despite several randomized controlled trials (RCTs) and cohort studies exploring the effects of CCBs on prognosis and exercise capacity in HFpEF patients, the findings have been inconsistent, likely due to limited statistical power and/or variations in study design. We aimed to conduct a systematic review and meta-analysis of studies on the effects of CCBs in HFpEF patients. The search of electronic databases identified 2 RCTs including 35 patients and 4 cohort studies including 25,078 patients. In cases of significant heterogeneity (I² > 50 %), data were pooled using a random-effects model; otherwise, a fixed-effects model was used. In pooled analysis of the cohort studies, use of CCBs was not associated with the risk of all-cause death (hazard ratio [95 % CI] = 0.913 [0.732, 1.139], P_random = 0.420) or hospitalization for heart failure (1.050 [0.970, 1.137], P_fix = 0.230). Separate analyses for dihydropyridine and non-dihydropyridine CCBs revealed similar results. In pooled analysis of the RCTs, verapamil increased exercise time (weighted mean difference [95 % CI] = 0.953 [0.109, 1.797] min; P_fix = 0.027) and decreased the congestive heart failure score (2.019 [1.673, 2.365] points; P_fix < 0.001) compared with placebo. In conclusion, in HFpEF patients, verapamil may improve exercise capacity and symptoms but use of CCBs, regardless of subclass, may not be associated with better prognosis. Our meta-analysis is limited by the inclusion of only several studies for each outcome and further research is necessary to confirm our findings.