Combination therapy of renin–angiotensin system inhibitors plus calcium channel blockers versus other two-drug combinations for hypertension: a systematic review and meta-analysis

Many randomized clinical trials (RCTs) have investigated the efficacy and safety of renin-angiotensin system inhibitors (RASIs) plus calcium channel blockers (CCBs), compared with other two-drug combinations, but systematic assessment in this aspect is still lacking. We carried out the present meta-analysis of randomized controlled trials to evaluate the long-term effect and safety of RASIs plus CCBs. Literatures were searched in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials in September 2014. A fixed-effect model was used to estimate the pooled effect of trials identified. Thirty-four trials with 41 694 patients were included. Compared with RASIs plus diuretics, RASIs plus CCBs decreased total cardiovascular (CV) events (relative risk (RR) 0.82, 95% confidence interval (CI): 0.75, 0.91, adjusted RR (ARR) 1.7%) and withdrawals due to adverse effect (WDAE) (RR 0.87, 95% CI: 0.80, 0.94, ARR 1.3%). Compared with CCBs plus diuretics, RASIs plus CCBs decreased WDAE (RR 0.63, 95% CI: 0.45, 0.90, ARR 1.1%). Our meta-analysis indicates that RASIs plus CCBs provide a superior safety and prevention of CV events to RASIs plus diuretics, whereas this combination is also safer than CCBs plus diuretics. We also raise a new hypothesis. More high-quality RCTs focused on hard end points with CV, cerebrovascular and renal events are needed to confirm the hypothesis we have brought out.