Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs: A Randomized Clinical Trial
Open accessAbstract
Importance: Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure–lowering therapies are available but the potential for maximizing benefit by personalized targeting of drug classes is unknown. Objective: To investigate and quantify the potential for targeting specific drugs to specific individuals to maximize blood pressure effects. Design, Setting, and Participants: A randomized, double-blind, repeated crossover trial in men and women with grade 1 hypertension at low risk for cardiovascular events at an outpatient research clinic in Sweden. Mixed-effects models were used to assess the extent to which individuals responded better to one treatment than another and to estimate the additional blood pressure lowering achievable by personalized treatment. Interventions: Each participant was scheduled for treatment in random order with 4 different classes of blood pressure–lowering drugs (lisinopril [angiotensin-converting enzyme inhibitor], candesartan [angiotensin-receptor blocker], hydrochlorothiazide [thiazide], and amlodipine [calcium channel blocker]), with repeated treatments for 2 classes. Main Outcomes and Measures: Ambulatory daytime systolic blood pressure, measured at the end of each treatment period. Results: There were 1468 completed treatment periods (median length, 56 days) recorded in 270 of the 280 randomized participants (54% men; mean age, 64 years). The blood pressure response to different treatments varied considerably between individuals (P < .001), specifically for the choices of lisinopril vs hydrochlorothiazide, lisinopril vs amlodipine, candesartan vs hydrochlorothiazide, and candesartan vs amlodipine. Large differences were excluded for the choices of lisinopril vs candesartan and hydrochlorothiazide vs amlodipine. On average, personalized treatment had the potential to provide an additional 4.4 mm Hg–lower systolic blood pressure. Conclusions and Relevance: These data reveal substantial heterogeneity in blood pressure response to drug therapy for hypertension, findings that may have implications for personalized therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02774460
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Based on previous studies, improved medication adherence or personalized antihypertensive treatment could have contributed to HBPM's effectiveness.
“Based on previous studies [77, 78], improved medication adherence or personalized antihypertensive treatment could have contributed to HBPM’s effectiveness.”
From Self-measurement of blood pressure at home using a cuff device for change in blood pressure levels: systematic review and meta-analysis (2025) · cites this paper as [78]
The ‘Evidence of the potential for personalized treatment’ section estimates that selecting an antihypertensive drug for the individual could improve blood-pressure reduction. The Discussion considers future continuous blood-pressure measurement as a way to compare treatments, but the paper does not establish that personalized treatment contributed to HBPM’s effectiveness. Its discussion of adherence also does not show that HBPM improved adherence. (LLM, conf=0.84)
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“Based on previous studies [77, 78], improved medication adherence or personalized antihypertensive treatment could have contributed to HBPM ’ s effectiveness.”
- Authors
- Sundström, J., Lind, L., Nowrouzi, S., Hagström, E., Held, C., Lytsy, P., Neal, B., Marttala, K., & Östlund, O.
- Affiliations
- Uppsala University (SE)
- UNSW Sydney (AU)
- Corresponding author
- Sundström, Johan
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2023-04-11
- Volume
- 329
- Issue
- 14
- Pages
- 1160
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC10091169
- OpenAlex
- W4364352257
- Cited by
- 84
- References
- 31
- Citations by year
- 2026: 21 · 2025: 24 · 2024: 27 · 2023: 12
- FWCI
- 16.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
- Funders
- Vetenskapsrådet
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- hypertension, antihypertensive drugs, personalized medicine, lisinopril, candesartan, hydrochlorothiazide, amlodipine, ACE inhibitors, angiotensin receptor blockers, thiazide diuretics, calcium channel blockers, ambulatory blood pressure, stage 1 hypertension
- MeSH terms
- Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Benzimidazoles, Biphenyl Compounds, Blood Pressure, Calcium Channel Blockers, Diuretics, Double-Blind Method, Female, Humans, Hydrochlorothiazide, Hypertension, Male, Middle Aged, Tetrazoles, Amlodipine, Lisinopril, Cross-Over Studies, Precision Medicine, Angiotensin Receptor Antagonists
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