Evidence map›Paper›PMID 36516076›Full record

Trial reportThe New England journal of medicine2022

Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events.

Areef Ishani, William C Cushman, Sarah M Leatherman, Robert A Lew, Patricia Woods, Peter A Glassman, Addison A Taylor, Cynthia Hau, Alison Klint, Grant D Huang and 4 more

Registry-linked trialOpen access · bronzeAbstract readComparative StudyPragmatic Clinical TrialRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02185417 (CSP #597 - Diuretic Comparison Project), which is not on this map. Cited by 63 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 7 pooled it
21.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02185417 phase3completednot on this map

CSP #597 - Diuretic Comparison Project

TypeinterventionalSponsorVA Office of Research and DevelopmentRan2016 to 2022Enrolled20,723ConditionsHypertensionArmsHydrochlorothiazide (HCTZ), Chlorthalidone (CTD)
3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 7 syntheses or guidelines pooled it, 143 citations in OpenAlex.

  1. The Japanese Society of Hypertension Guidelines for the management of elevated blood pressure and hypertension 2025 (JSH2025).Hypertension research : official journal of the Japanese Society of Hypertension · 2026
    Guideline
  2. Guideline
  3. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2025
    Guideline
  4. Hypertension Canada guideline for the diagnosis and treatment of hypertension in adults in primary care.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2025
    Guideline
  5. Guideline
  6. Pooled it
  7. Guideline
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Challenges and Perspectives in Optimising the Treatment of Arterial Hypertension: Role of the Ramipril-Amlodipine-Hydrochlorothiazide Single-Pill Combination.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2026
    Review
  15. Article
  16. Pitfalls in the pharmacotherapy of hypertension.Clinical medicine (London, England) · 2026
    Review
  17. Designing Pragmatic Trials to Better Inform Nephrology Practice.Journal of the American Society of Nephrology : JASN · 2026
    Article
  18. Review
  19. Comparative efficacy and safety of chlorthalidoneWorld journal of cardiology · 2026
    Article
  20. Article

3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 7 institutions in 1 country.

Areef IshaniFrom Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).
William C CushmanFrom Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).
Sarah M LeathermanFrom Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).ORCID 0000-0002-9821-9646
Robert A LewFrom Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).
Patricia WoodsFrom Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).
Peter A GlassmanFrom Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).
Addison A TaylorFrom Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).
Cynthia HauFrom Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).
Alison KlintFrom Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).
Grant D HuangFrom Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).
Mary T BrophyFrom Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).
Louis D FioreFrom Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).
Ryan E FergusonFrom Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).ORCID 0000-0001-8695-5024
Diuretic Comparison Project Writing Group
Boston University · USVA Boston Healthcare System · USBaylor College of Medicine · USMichael E. DeBakey VA Medical Center · USUniversity of Minnesota · USUniversity of Tennessee Health Science Center · USVA Office of Research and Development · US

Funding

CSP VA
6 · The paper itself

Abstract

backgroundWhether chlorthalidone is superior to hydrochlorothiazide for preventing major adverse cardiovascular events in patients with hypertension is unclear.

methodsIn a pragmatic trial, we randomly assigned adults 65 years of age or older who were patients in the Department of Veterans Affairs health system and had been receiving hydrochlorothiazide at a daily dose of 25 or 50 mg to continue therapy with hydrochlorothiazide or to switch to chlorthalidone at a daily dose of 12.5 or 25 mg. The primary outcome was a composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer-related death. Safety was also assessed.

resultsA total of 13,523 patients underwent randomization. The mean age was 72 years. At baseline, hydrochlorothiazide at a dose of 25 mg per day had been prescribed in 12,781 patients (94.5%). The mean baseline systolic blood pressure in each group was 139 mm Hg. At a median follow-up of 2.4 years, there was little difference in the occurrence of primary-outcome events between the chlorthalidone group (702 patients [10.4%]) and the hydrochlorothiazide group (675 patients [10.0%]) (hazard ratio, 1.04; 95% confidence interval, 0.94 to 1.16; P = 0.45). There were no between-group differences in the occurrence of any of the components of the primary outcome. The incidence of hypokalemia was higher in the chlorthalidone group than in the hydrochlorothiazide group (6.0% vs. 4.4%, P<0.001).

conclusionsIn this large pragmatic trial of thiazide diuretics at doses commonly used in clinical practice, patients who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or non-cancer-related deaths than patients who received hydrochlorothiazide. (Funded by the Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT02185417.).

Indexed as

ChlorthalidoneHydrochlorothiazideHypertensionAgedAntihypertensive AgentsBlood PressureCardiovascular DiseasesDiureticsHumansSodium Chloride Symporter InhibitorsAntihypertensive AgentsChlorthalidoneDiureticsHydrochlorothiazideSodium Chloride Symporter Inhibitors

Identifiers

PMID36516076
OpenAlexW4311448277

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.