Comparison of Cardiovascular Events Among Users of Different Classes of Antihypertension Medications: A Systematic Review and Network Meta-analysis

Abstract

Importance: Antihypertension medications have been associated with prevention of cardiovascular events, although less is known about the comparative effectiveness of different medication classes.

Objective: To compare contemporary aggregated first-in-trial cardiovascular events among patients with hypertension and no substantial comorbidities.

Data sources: The PubMed, Embase, and Cochrane Library databases were systematically searched for articles published between January 1, 1990, and October 24, 2017.

Study selection: Randomized clinical trials that tested commonly used antihypertension medications (angiotensin-converting enzyme inhibitors, dihydropyridine calcium channel blockers, nondihydropyridine calcium channel blockers, β-blockers, angiotensin receptor blockers, and diuretics) and that reported selected cardiovascular outcomes for at least 6 months of follow-up.

Data extraction and synthesis: The analysis was conducted from October 2017 to December 2019. Two reviewers extracted the number of cardiovascular events at the end of treatment for all study groups. For each outcome, a frequentist network meta-analysis was used to compare risk reductions between medication classes (random-effects models weighted by the inverse variance). The dose-response association between a 10-mm Hg reduction of systolic blood pressure and a 5-mm Hg reduction of diastolic blood pressure and the risk of first-in-trial cardiovascular events was estimated.

Main outcomes and measures: First-in-trial cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and revascularization.

Results: In this systematic review and network meta-analysis, data were pooled from 46 eligible clinical trials (248 887 total participants with a mean [SD] age of 65.6 [5.8] years; 52.8% men). In the network meta-analysis, compared with placebo, angiotensin-converting enzyme inhibitors, dihydropyridine calcium channel blockers, and thiazide diuretics were reported to be similarly effective in reducing overall cardiovascular events (25%), cardiovascular death (20%), and stroke (35%); angiotensin-converting enzyme inhibitors were reported to be the most effective in reducing the risk of myocardial infarction (28%); and diuretics were reported to be the most effective in reducing revascularization (33%). In the metaregression analyses, each 10-mm Hg reduction in systolic blood pressure and 5-mm Hg reduction in diastolic blood pressure was significantly associated with a lower risk of cardiovascular death, stroke, and overall cardiovascular events.

Conclusions and relevance: In this network meta-analysis of clinical trials of patients with hypertension and no substantial comorbidities, different classes of antihypertension medications were associated with similar benefits in reducing cardiovascular events. Future studies should compare the effectiveness of combinations of antihypertension medications in reducing cardiovascular events.

Figure 1.. PRISMA Diagram of Literature Search and Selection

Reasons for exclusion were not categorized by individual article because each article may have met multiple exclusion criteria.

Figure 2.. Network Plot of Antihypertension Medications

ACEi indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, β-blocker; DH CCB, dihydropyridine calcium channel blocker; and non–DH CCB, nondihydropyridine calcium channel blocker.

Figure 3.. Network Meta-analysis Comparing Single Class of Antihypertension Medications With Placebo for Treatment of Cardiovascular Events

ACE indicates angiotensin-converting enzyme; ARB, angiotensin receptor blocker; DH CCB, dihydropyridine calcium channel blocker; and error bars, 95% CI.