Benefits and harms of lower blood pressure treatment targets: systematic review and meta-analysis of randomised placebo-controlled trials

OBJECTIVES: To assess the effect of antihypertensive treatment in the 130–140 mm Hg systolic blood pressure range. DESIGN: Systematic review and meta-analysis. INFORMATION SOURCES: PubMed, CDSR and DARE were searched for the systematic reviews, which were manually browsed for clinical trials. PubMed and Cochrane Central Register of Controlled Trials were searched for trials directly in February 2018. ELIGIBILITY CRITERIA: Randomised double-blind trials with ≥1000 patient-years of follow-up, comparing any antihypertensive agent against placebo. DATA EXTRACTION AND RISK OF BIAS: Two reviewers extracted study-level data, and assessed risk of bias using Cochrane Collaborations risk of bias assessment tool, independently. MAIN OUTCOMES AND MEASURES: Primary outcomes were all-cause mortality, major cardiovascular events and discontinuation due to adverse events. Secondary outcomes were cardiovascular mortality, myocardial infarction, stroke, heart failure, hypotension-related adverse events and renal impairment. RESULTS: Eighteen trials, including 92 567 participants (34% women, mean age 63 years), fulfilled the inclusion criteria. Primary preventive antihypertensive treatment was associated with a neutral effect on all-cause mortality (relative risk 1.00, 95% CI 0.95 to 1.06) and major cardiovascular events (1.01, 0.96 to 1.06), but an increased risk of discontinuation due to adverse events (1.23, 1.03 to 1.47). None of the secondary efficacy outcomes were significantly reduced, but the risk of hypotension-related adverse events increased with treatment (1.71, 1.32 to 2.22). In coronary artery disease secondary prevention, antihypertensive treatment was associated with reduced risk of all-cause mortality (0.91, 0.83 to 0.99) and major cardiovascular events (0.85, 0.77 to 0.94), but doubled the risk of adverse events leading to discontinuation (2.05, 1.62 to 2.61). CONCLUSION: Primary preventive blood pressure lowering in the 130–140 mm Hg systolic blood pressure range adds no cardiovascular benefit, but increases the risk of adverse events. In the secondary prevention, benefits should be weighed against harms. PROSPERO REGISTRATION NUMBER: CRD42018088642.