COMPARATIVE EFFICACY AND ACCEPTABILITY OF ANTIHYPERTENSIVE DRUG CLASS COMBINATIONS FOR CARDIOVASCULAR DISEASE PREVENTION: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

Abstract

Objective: European guidelines recommend combination therapy for most hypertensive patients, but direct comparisons between major drug class combinations are lacking. Our aim was to compare the efficacy and acceptability of different drug class combinations. Design and method: We performed a systematic review and network meta-analysis guided by the recommendations from the Cochrane collaboration. We included all trials assessing any antihypertensive drug combination against another combination, single agent or placebo, with at least 1000 patient-years of follow-up in each treatment arm. Risk of bias was assessed using Cochrane Collaborations RoB2 tool, excluding trials at high risk of bias from the analysis. Odds ratios from individual trials were pooled using random-effects network meta-analysis, with composite major cardiovascular events as the primary outcome for efficacy, and treatment discontinuation as the primary outcome for acceptability. Results: 85 trials, including 406 067 participants followed for an average of 4.0 years, were included in the analysis. Mean age was 64.0 years and 41% percent were women. Overall, 15 different drug classes, drug class combinations and placebo were included in the network. Direct comparisons between dug class combinations were sparse, and there were signs of inconsistency between direct and indirect comparisons, particularly for acceptability. The main results are presented in figure 1. Combination therapy using renin-angiotensin system inhibitors (RASi) and calcium channel blockers (CCB) appeared most effective in preventing major cardiovascular events, followed by a combination of thiazide and potassium-sparring diuretics. The combination of RASi and diuretics appeared least effective among combinations studied. For acceptability, no combination differed significantly compared to placebo, although combinations including an angiotensin receptor blocker (ARB) trended towards being more acceptable, and combinations including and angiotensin-converting enzyme inhibitor trended towards being less acceptable, compared to placebo. Conclusions: In this first network meta-analysis of antihypertensive drug combinations, RASi + CCB appears most effective in preventing major cardiovascular events. Based on a more beneficial acceptability profile, combinations including ARB may be preferred over combinations including ACEi, although these findings should be interpreted with caution due to lack of direct comparisons.