Effects of Intensive Blood Pressure Treatment on Orthostatic Hypotension : A Systematic Review and Individual Participant-based Meta-analysis

Abstract

Background: Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH).

Purpose: To examine the effects of intensive BP-lowering treatment on OH in hypertensive adults.

Data sources: MEDLINE, EMBASE, and Cochrane CENTRAL from inception through 7 October 2019, without language restrictions.

Study selection: Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) that involved more than 500 adults with hypertension or elevated BP and that were 6 months or longer in duration. Trial comparisons were groups assigned to either less intensive BP goals or placebo, and the outcome was measured OH, defined as a decrease of 20 mm Hg or more in systolic BP or 10 mm Hg or more in diastolic BP after changing position from seated to standing.

Data extraction: 2 investigators independently abstracted articles and rated risk of bias.

Data synthesis: 5 trials examined BP treatment goals, and 4 examined active agents versus placebo. Trials examining BP treatment goals included 18 466 participants with 127 882 follow-up visits. Trials were open-label, with minimal heterogeneity of effects across trials. Intensive BP treatment lowered risk for OH (odds ratio, 0.93 [95% CI, 0.86 to 0.99]). Effects did not differ by prerandomization OH (P for interaction = 0.80). In sensitivity analyses that included 4 additional placebo-controlled trials, overall and subgroup findings were unchanged.

Limitations: Assessments of OH were done while participants were seated (not supine) and did not include the first minute after standing. Data on falls and syncope were not available.

Conclusion: Intensive BP-lowering treatment decreases risk for OH. Orthostatic hypotension, before or in the setting of more intensive BP treatment, should not be viewed as a reason to avoid or de-escalate treatment for hypertension.

Primary funding source: National Heart, Lung, and Blood Institute, National Institutes of Health. (PROSPERO: CRD42020153753).

Figure. Effects of BP treatment on risk for orthostatic hypotension, by study.

Pooled effects are organized by the 5 primary studies (primary effect) and with the 4 additional trials identified through our search. The size of each point estimate is weighted by the number of follow-up visits with orthostatic hypotension assessments. AASK = African American Study of Kidney Disease and Hypertension; ACCORD BP = Action to Control Cardiovascular Risk in Diabetes: Blood Pressure; BP = blood pressure; SPRINT = Systolic Blood Pressure Intervention Trial; SPS3 = Secondary Prevention of Small Subcortical Strokes; UKPDS = U.K. Prospective Diabetes Study; HYVET = Hypertension in the Very Elderly Trial; OR = odds ratio; SHEP = Systolic Hypertension in the Elderly Program; Syst-Eur = Systolic Hypertension in Europe; TOMHS = Treatment of Mild Hypertension Study.

Appendix Figure.. Study search and selection.

Left. Search process for trials comparing BP treatment goals. These 5 trials were included in the primary analysis. Right. Results of contact of investigators of BP trials, leading to the identification of the 4 placebo-controlled trials included in secondary analyses. BP = blood pressure.