Antihypertensive Efficacy of Hydrochlorothiazide vs Chlorthalidone Combined with Azilsartan Medoxomil
Abstract
Background Chlorthalidone has proven efficacy to reduce cardiovascular morbidity and mortality, yet it is infrequently used in practice. This study provides a direct comparison of chlorthalidone with hydrochlorothiazide, each combined with the angiotensin receptor blocker azilsartan medoxomil, on blood pressure reduction and control rates.Methods This is a randomized, double-blind, titrate-to-target blood pressure trial comparing the single-pill combination of azilsartan medoxomil and chlorthalidone versus co-administration of azilsartan medoxomil and hydrochlorothiazide in participants with stage 2 primary hypertension. After 2 weeks of treatment with azilsartan medoxomil 40 mg alone, all participants also received 12.5 mg of diuretic for 4 weeks (up to week 6) and were titrated to 25 mg for another 4 weeks (up to week 10) if they failed to achieve target blood pressure. The primary end point was change in clinic systolic blood pressure. Target blood pressure was defined as clinic blood pressure <140/90 mm Hg for participants without diabetes or chronic kidney disease or <130/80 mm Hg for participants with diabetes or chronic kidney disease.Results The mean age of the 609 participants was 56.4 years, and the mean baseline clinic blood pressure was 164.6/95.4 mm Hg. The primary end point analysis at week 6 demonstrated a greater reduction of clinic systolic blood pressure for the chlorthalidone (-35.1 mm Hg) versus hydrochlorothiazide combination (-29.5 mm Hg) (mean difference, -5.6 mm Hg; 95% confidence interval, -8.3 to -2.9; P <.001). The mean difference in 24-hour ambulatory systolic blood pressure at week 6 was -5.8 mm Hg (95% confidence interval, -8.4 to -3.2; P <.001), favoring the azilsartan medoxomil/chlorthalidone group. The percentage of participants achieving target clinic blood pressure at week 6 was greater for the chlorthalidone versus hydrochlorothiazide combination (64.1% vs 45.9%, P <.001). Drug discontinuations due to adverse events were not statistically significantly different between groups (9.3% vs 7.3%, P = .38), and hypokalemia was uncommon in both groups.Conclusions Chlorthalidone combined with azilsartan medoxomil provides better blood pressure reduction and a higher likelihood of achieving blood pressure control than hydrochlorothiazide combined with azilsartan medoxomil. This benefit occurred without a difference in safety measurements.
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Comparative studies show an additional SBP reduction of 7 to 8 mm Hg simply by switching from hydrochlorothiazide to the same daily dose of chlorthalidone.
“Comparative studies show an additional SBP reduction of 7 to 8 mm Hg simply by switching from hydrochlorothiazide to the same daily dose of chlorthalidone.370–372”
From Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association (2018) · cites this paper as [372]
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- Authors
- Bakris, G. L., Sica, D., White, W. B., Cushman, W. C., Weber, M. A., Handley, A., Song, E., & Kupfer, S.
- Affiliations
- University of Chicago (US)
- Virginia Commonwealth University (US)
- University of Connecticut (US)
- University of Tennessee Health Science Center (US)
- SUNY Downstate Health Sciences University (US)
- Takeda (United States) (US)
- Corresponding author
- Bakris, George L.
- Venue
- The American Journal of Medicine
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 125
- Issue
- 12
- Pages
- 1229.e1-1229.e10
- ISSN
- 0002-9343 (ISSN-L)
- OpenAlex
- W2052409620
- Cited by
- 90
- References
- 26
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 8 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 6 · 2017: 11 · 2016: 6 · 2015: 10 · 2014: 6 · 2013: 15 · 2012: 1
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Keywords
- chlorthalidone, hydrochlorothiazide, azilsartan medoxomil, combination antihypertensive therapy, stage 2 hypertension, blood pressure control, diuretics, angiotensin receptor blockers, single-pill combination, ambulatory blood pressure, systolic blood pressure reduction
- MeSH terms
- Aged, Antihypertensive Agents, Benzimidazoles, Chlorthalidone, Creatinine, Double-Blind Method, Drug Combinations, Drug Therapy, Combination, Female, Humans, Hydrochlorothiazide, Hypertension, Male, Middle Aged, Oxadiazoles, Potassium, Systole, Blood Pressure Monitoring, Ambulatory, Angiotensin II Type 1 Receptor Blockers
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