More Versus Less Intensive Blood Pressure-Lowering Strategy: Cumulative Evidence and Trial Sequential Analysis

Several randomized trials compared a more versus less intensive blood pressure-lowering strategy on the risk of major cardiovascular events and death. Cumulative meta-analyses and trial sequential analyses can establish whether and when firm evidence favoring a specific intervention has been reached from accrued literature. Therefore, we conducted a cumulative trial sequential analysis of 18 trials that randomly allocated 53 405 patients to a more or less intensive blood pressure-lowering strategy. We sought to ascertain the extent to which trial evidence added to previously accrued data. Outcome measures were stroke, myocardial infarction, heart failure, cardiovascular death, and all-cause death. Achieved blood pressure was 7.6/4.5 mm Hg lower with the more intensive than the less intensive blood pressure-lowering strategy. For stroke and myocardial infarction, the cumulative Z curve crossed the efficacy monitoring boundary solely after the SPRINT (Systolic Blood Pressure Intervention Trial) study, thereby providing firm evidence of superiority of a more intensive over a less intensive blood pressure-lowering strategy. For cardiovascular death and heart failure, the cumulative Z curve crossed the conventional significance boundary, but not the sequential monitoring boundary, after SPRINT. For all-cause death, the SPRINT trial pushed the cumulative Z curve away from the futility area, without reaching the conventional significance boundary. We conclude that evidence accrued to date strongly supports the superiority of a more intensive versus a less intensive blood pressure-lowering strategy for prevention of stroke and myocardial infarction. Cardiovascular death and heart failure are likely to be reduced by a more intensive blood pressure-lowering strategy, but evidence is not yet conclusive.