Synergistic effects of blood pressure-lowering drugs and statins: systematic review and meta-analysis

BACKGROUND: Synergistic effects of blood pressure-lowering 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 pressure-lowering 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 pressure-lowering drug/more intense blood pressure-lowering 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 pressure-lowering 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.