Synergistic Effects Of Blood Pressure-Lowering Drugs And Statins: Systematic Review And Meta-Analysis

Background Synergistic effects of blood pressurelowering drugs and statins are unknown, but are key to risk-based treatment decision strategies and fixed-combination polypills.Objective We conducted a systematic literature review and meta-analysis to test the hypothesis that the combined relative effects of blood pressurelowering drugs and statins on cardiovascular outcomes are multiplicative.Study selection Two persons independently searched five data sources and hand-searched reference lists from earliest available to December 2017. We included factorial trials with at least two randomised interventions including one statin versus placebo factor and one blood pressurelowering drug/more intense blood pressurelowering regimen versus placebo/less intense regimen factor, and reported cardiovascular events or mortality as outcomes. We tested interactions as departures from additivity or multiplicativity using mixed-effects logistic regression models.Findings Seven out of 1017 screened studies fulfilled the selection criteria, contributing a total of 27 020 patients with 857 major cardiovascular events and 725 deaths. The relative risk reduction of major cardiovascular events with active/more intense blood pressure-lowering regimen was not materially different in subgroups randomised to statins (risk ratio 0.81, 95% CI 0.66 to 1.00) or placebo (0.94, 0.79 to 1.11). Likewise, statin effects were not substantially different in subgroups randomised to active/more intense blood pressurelowering regimen (0.69, 0.57 to 0.85) or placebo/ less intense regimen (0.80, 0.67 to 0.96). No departures from either additivity or multiplicativity were observed. Heterogeneity was low.Conclusions The combined relative effects of blood pressure-lowering drugs and statins on cardiovascular events were multiplicative. This supports risk-based treatment decision strategies and fixed-combination polypills.