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Juraschek SP, Hu JR, Cluett JL, et al. Effects of Intensive Blood Pressure Treatment on Orthostatic Hypotension : A Systematic Review and Individual Participant-based Meta-analysis. Ann Intern Med. 2020 Sep 10. doi: 10.7326/M20-4298. (Systematic review)

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. (PROSPERO: CRD42020153753).

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: Two investigators independently abstracted articles and rated risk of bias.

DATA SYNTHESIS: Five 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.

Discipline Area Score
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Internal Medicine 6 / 7
Cardiology 5 / 7
Comments from MORE raters

Cardiology rater

In general, the treatment goals for hypertensive patients depends on the practitioner. While some aim for a normal BP, others aim for some lowering of BP. It is interesting that among all the RCTs for treating hypertension, the authors could find 9 trials with more than 500 patients where orthostatic hypotension was clearly defined. Useful study.

General Internal Medicine-Primary Care(US) rater

This is certain to become a highly cited article, an absolute pearl of a study. Some limitations, of course, but the patient-level data and overall methods lend strong validity to the conclusions. Another great example of how research can produce seemingly paradoxical conclusions, and another example of how research can reveal that our physiologic-based thinking may not be correct (just as when we thought beta-blockers were not beneficial in CHF, or when we thought prophylactic lidocaine was helpful in acute MI, or low-dose dopamine in acute renal failure, etc). Supports so much of what we love about EBM.

Internal Medicine rater

This is an interesting and important study. Although it doesn’t address the risks for falls or syncope (or signs suggesting an increased risk), orthostatic hypotension can be a significant side effect that interferes with patient function.

Internal Medicine rater

The paper with specific focus on orthostatic hypotension (defined as blood pressure change from seated to standing positions) is well written except for a few limitations as outlined in the Discussion. This substantially reduces the opportunity to find patients who demonstrate significant reduction in blood pressure from supine to standing.
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