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Introduction: Blood pressure lowering drugs help prevent cardiovascular events though less is known about the comparative effectiveness of different drug classes. We aimed to compare the effect of different blood pressure lowering drugs classes on cardiovascular risk.Hypothesis: We hypothesized that the cardiovascular preventive effects of blood pressure lowering drugs would vary among different types of drug classes.Methods: PubMed, EMBASE, and Cochrane Library databases were searched for articles published between January 1, 1990 and June 30, 2014. Study eligibility criteria included randomized controlled trials testing blood pressure-lowering drugs, including angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, calcium-channel blockers, beta-blockers, and thiazide diuretics that reported cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, coronary revascularization and composite cardiovascular events) with at least 6 months of follow-up. Data from studies that met inclusion criteria were independently extracted by two reviewers using a standardized extraction form. For each outcome, a Frequentist, random effects network meta-analysis model was used to compare risk reductions between drug classes. The relative ranking probability of each blood pressure lowering drug class being the most effective was estimated using rankogram curves, surface under the cumulative ranking curves, and mean ranks.Results: A total of 102 trials that included 415,047 participants (mean age 65.1 years, 60.0% male) met inclusion criteria. Compared to placebo, blood pressure lowering drugs reduced the risk of composite cardiovascular events by 11-18% in aggregate. Calcium channel blockers were the most effective in reducing composite cardiovascular events risk (RR=0.82, 95% CI: 0.77, 0.88), stroke (RR=0.68, 95% CI: 0.61, 0.75) and revascularization (RR=0.84, 95% CI: 0.77, 0.92); angiotensin-converting-enzyme inhibitors were the most effective in reducing cardiovascular death (RR=0.85, 95% CI: 0.80, 0.91) and myocardial infarction (RR=0.83, 95% CI: 0.77, 0.91). Effects of drugs were influenced by blood pressure, where each 10mmHg reduction in systolic and diastolic blood pressure, regardless of drug class, was associated with a 2.5% (95% CI: -3.8, -1.2) and 5.4% (95% CI: -8.0, -2.4) lower risk of composite cardiovascular events, respectively.Conclusion: Angiotensin-converting-enzyme inhibitors had an advantage over other blood pressure lowering drugs in preventing myocardial infarction and cardiovascular death, while calcium channel blockers were more effective in preventing overall cardiovascular events, stroke and revascularization. Future studies should compare the effectiveness of combination of drug classes in reducing cardiovascular events.