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

Abstract

Objective: No single trial has compared all major antihypertensive drug classes head-to-head and current guidelines give different recommendations for first-line agents. Our aim was to assess the efficacy for cardiovascular disease prevention as well as acceptability across all antihypertensive drug classes. 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 agent against another 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, and trials at high risk of bias were excluded 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 from 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. There were some signs of inconsistency between direct and indirect comparisons, particularly for acceptability. The main results are presented in figure 1. Angiotensin-converting enzyme inhibitors (ACEi), angiotensin-receptor blockers (ARB), and calcium channel blockers (CCB) all reduced the risk of major cardiovascular events compared to placebo. Diuretics showed a similar trend, whereas beta-blockers (BB) and renin inhibitors did not. For acceptability, ARB and CCB were comparable to placebo, diuretics showed a non-significant trend towards more discontinuations, whereas ACEi, BB and alpha-blockers were significant more prone to treatment discontinuation compared to placebo and other agents. Conclusions: This is the most comprehensive network meta-analysis of antihypertensive agents to date. Our findings indicate that ACEi, ARB and CCB are the most effective agents in preventing major cardiovascular events. Based on a more beneficial acceptability profile, ARB and CCB may be considered most appropriate as first-line agents, although these findings should be interpreted with caution due inconsistency.