Effects of Anti-Hypertensive Agents on Orthostatic Changes: Secondary Analysis of the Treatment of Mild Hypertension Study (TOMHS)
In brief
Doxazosin raises orthostatic hypotension odds 45%, lowers orthostatic hypertension odds 34%
In a secondary analysis of 897 adults in a randomized hypertension trial, doxazosin was linked to 45% higher odds of orthostatic hypotension and 34% lower odds of orthostatic hypertension than placebo. Amlodipine and chlorthalidone were associated with lower odds of orthostatic hypotension over time, but the findings need to be weighed against each drug's other effects when selecting treatment.
- Journal
- American journal of hypertension (Q1)
- Published
- 1 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Esther Y Liu, Grace Lee, Md Marufuzzaman Khan, Aldis Petriceks, Hannah Col, Mingyu Zhang, et al.
- PMID
- 42820774
- DOI
- 10.1093/ajh/hpag119
Why clinicians should know about it
- Picked for Internal Medicine (top studies of the week, 25 October 2026): Secondary analysis of antihypertensive effects on orthostatic changes
Abstract
BACKGROUND: Orthostatic hypotension (OH) and orthostatic hypertension (OHT) are common among adults with hypertension and may complicate antihypertensive treatment selection.However, the impact of specific antihypertensive agents on orthostatic blood pressure (BP) responses and risk of OH or OHT remains incompletely characterized. METHODS: We performed a secondary analysis of the Treatment of Mild Hypertension Study (TOMHS), a multicenter randomized clinical trial (1987-1993). A total of 902 adults aged 45-69 years with diastolic BP 90-99 mmHg were randomized to acebutolol, amlodipine, chlorthalidone, doxazosin, enalapril, or placebo. Orthostatic BP change (standing minus seated BP) was assessed at randomization, 1 month, and every 3 months up to 54 months. OH was defined as a systolic BP decrease ≥20 mmHg or diastolic BP decrease ≥10 mmHg; OHT was defined as a systolic BP increase ≥20 mmHg or diastolic BP increase ≥10 mmHg. Generalized estimating equations evaluated associations between agents and orthostatic BP changes overall, by baseline BP, and over time. RESULTS: Among 897 participants with orthostatic BP measurements (mean age 54.8 years; 38.5% female; 19.6% Black), doxazosin increased odds of OH (OR 1.45; 95% CI, 1.05-2.02) and reduced odds of OHT (OR 0.66; 95% CI, 0.51-0.86) versus placebo. Chlorthalidone reduced OHT among participants with baseline OHT (P=0.018). Amlodipine and doxazosin attenuated orthostatic systolic BP changes across baseline orthostatic BP change strata. Over time, amlodipine and chlorthalidone reduced odds of OH (P=0.001, 0.044). CONCLUSIONS: Specific antihypertensive agents demonstrated distinct effects on orthostatic BP regulation. Consideration of orthostatic effects during antihypertensive selection may help individualize therapy, improve hemodynamic stability, and optimize treatment for patients at risk of orthostatic dysregulation.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.