Effects of blood pressure lowering on outcome incidence in hypertension: 7. Effects of more vs. less intensive blood pressure lowering and different achieved blood pressure levels - Updated overview and meta-analyses of randomized trials

Background and objectives: Previous meta-analyses of our group have investigated the cardiovascular effects of more vs. less intense blood pressure (BP) treatment and the BP levels to be achieved by treatment. A few additional trials have been completed recently, particularly the large SPRINT study. Updating of the previous meta-analyses has been done with the objective of further clarifying the practical question of BP targets of antihypertensive treatment. Methods: Among randomized-controlled trials (RCTs) of BP lowering treatment between 1966 and 2015, 16 (52235 patients) compared more vs. less intense treatment and fulfilled other preset criteria, and in 34 (138127 patients) SBP in the active (vs. placebo) or the more (vs. less) intense treatment was below (vs., respectively, above) three predetermined cutoffs. For their meta-analyses risk ratios (RR) and 95% confidence intervals, standardized to -10/-5mmHg SBP/DBP reduction, and absolute risk reductions of seven fatal and nonfatal outcomes were calculated. Results: More intense BP lowering significantly reduced risk of stroke [RR 0.71 (0.60-0.84)], coronary events [0.80 (0.68-0.95)], major cardiovascular events [0.75 (0.68-0.85)] and cardiovascular mortality [0.79 (0.63-0.97)], but not heart failure and all-cause death. When the 16 RCTs were stratified according to cardiovascular death risk, relative risk reduction did not differ between strata, but absolute risk reduction increased with cardiovascular risk, though the residual risk also increased. Stratification of the 34 RCTs according to the three different SBP cutoffs (150, 140 and 130mmHg) showed that a SBP/DBP difference of -10/-5mmHg across each cutoff significantly reduced risk of all outcomes to the same proportion (relative risk reduction), but absolute risk reduction of most outcomes had a significant trend to decrease at lower cutoffs. Conclusion: Updating of previous meta-analyses indicates that more vs. less intense BP lowering can reduce not only stroke and coronary events, but also cardiovascular mortality. Including data from recent RCTs also shows that all major outcomes can be reduced by lowering SBP a few mmHg below vs. above 130mmHg, but absolute risk reduction becomes smaller, suggesting patients at lower initial SBP were at a lower level of cardiovascular risk.