Abstract

Background: Intensive blood pressure (BP) treatment reduces the risk of cardiovascular disease, but there are ongoing concerns that it also might be harmful by increasing the risk of orthostatic hypotension (OH). However, individual trials have been inconclusive. Methods: In this individual participant data meta-analysis, we systematically reviewed MEDLINE, EMBASE, and CENTRAL databases through October 7, 2019 for randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) on measured OH. OH was defined as a drop in SBP ≥20 mmHg or DBP ≥10 mmHg after changing positions from seated to standing. Ultimately, five trials of BP treatment goal were identified. Effects were examined overall and in subgroups of baseline characteristics, including diabetes, standing BP pre-randomization (<110 vs ≥110 mm Hg), and pre-randomization OH. Results: There were 18,466 participants with 127,998 follow-up visits. Most trials demonstrated low risk of bias with minimal heterogeneity of effects across trials ( I 2 = 0.0%). Intensive BP treatment significantly lowered risk of OH (OR 0.93; 95% CI: 0.86, 0.99). Effects were strongest among adults without diabetes (OR 0.90 vs 1.10; P -interaction = 0.015) and adults with lower standing SBP (OR 0.66 for <110 mmHg vs 0.96 for ≥110 mmHg; P -interaction = 0.02). Effects did not differ by pre-randomization OH ( P -interaction = 0.80). In sensitivity analyses that included 4 additional placebo-controlled trials, overall and subgroup findings were unchanged ( Figure ). Conclusion: OH prior to or in the setting of more intensive BP treatment should not be viewed as a reason to avoid or to de-escalate treatment for hypertension.

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