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.