Chlorthalidone Versus Hydrochlorothiazide: A New Kind of Veterans Affairs Cooperative Study

Ideas and Opinions1 November 2016Chlorthalidone Versus Hydrochlorothiazide: A New Kind of Veterans Affairs Cooperative StudyFrank A. Lederle, MD, William C. Cushman, MD, Ryan E. Ferguson, ScD, MPH, Mary T. Brophy, MD, MPH, and Louis D. Fiore, MD, MPHFrank A. Lederle, MDFrom the Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota; Veterans Affairs Medical Center, Memphis, Tennessee; and Veterans Affairs Boston Healthcare System, Boston, Massachusetts., William C. Cushman, MDFrom the Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota; Veterans Affairs Medical Center, Memphis, Tennessee; and Veterans Affairs Boston Healthcare System, Boston, Massachusetts., Ryan E. Ferguson, ScD, MPHFrom the Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota; Veterans Affairs Medical Center, Memphis, Tennessee; and Veterans Affairs Boston Healthcare System, Boston, Massachusetts., Mary T. Brophy, MD, MPHFrom the Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota; Veterans Affairs Medical Center, Memphis, Tennessee; and Veterans Affairs Boston Healthcare System, Boston, Massachusetts., and Louis D. Fiore, MD, MPHFrom the Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota; Veterans Affairs Medical Center, Memphis, Tennessee; and Veterans Affairs Boston Healthcare System, Boston, Massachusetts.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-1208 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Thiazide-type diuretics, including hydrochlorothiazide and chlorthalidone, have been used to treat hypertension for more than 50 years. The Seventh Report of the Joint Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (1) and the current Veterans Affairs (VA) and Department of Defense guidelines consider them first-line treatment for hypertension. Hydrochlorothiazide is the most commonly used agent, accounting for 95% of thiazide prescriptions in VA patients compared with 2.5% for chlorthalidone (2). However, indirect evidence summarized in a recent network meta-analysis (3) suggests that chlorthalidone may be more effective than hydrochlorothiazide in preventing cardiovascular events. Possible mechanisms for ...References1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-72. PMID: 12748199 CrossrefMedlineGoogle Scholar2. Ernst ME, Lund BC. Renewed interest in chlorthalidone: evidence from the Veterans Health Administration. J Clin Hypertens (Greenwich). 2010;12:927-34. PMID: 21122058 doi:10.1111/j.1751-7176.2010.00373.x CrossrefMedlineGoogle Scholar3. Roush GC, Holford TR, Guddati AK. Chlorthalidone compared with hydrochlorothiazide in reducing cardiovascular events: systematic review and network meta-analyses. Hypertension. 2012;59:1110-7. PMID: 22526259 doi:10.1161/HYPERTENSIONAHA.112.191106 CrossrefMedlineGoogle Scholar4. Ernst ME, Carter BL, Goerdt CJ, Steffensmeier JJ, Phillips BB, Zimmerman MB, et al. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension. 2006;47:352-8. PMID: 16432050 CrossrefMedlineGoogle Scholar5. Woodman R, Brown C, Lockette W. Chlorthalidone decreases platelet aggregation and vascular permeability and promotes angiogenesis. Hypertension. 2010;56:463-70. PMID: 20625077 doi:10.1161/HYPERTENSIONAHA.110.154476 CrossrefMedlineGoogle Scholar6. D'Avolio L, Ferguson R, Goryachev S, Woods P, Sabin T, O'Neil J, et al. Implementation of the Department of Veterans Affairs' first point-of-care clinical trial. J Am Med Inform Assoc. 2012;19:e170-6. PMID: 22366293 CrossrefMedlineGoogle Scholar7. Wright JT, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, et al; SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-16. PMID: 26551272 doi:10.1056/NEJMoa1511939 CrossrefMedlineGoogle Scholar8. Hernandez AF, Fleurence RL, Rothman RL. The ADAPTABLE Trial and PCORnet: shining light on a new research paradigm. Ann Intern Med. 2015;163:635-6. PMID: 26301537. doi:10.7326/M15-1460 LinkGoogle Scholar9. Pletcher MJ, Lo B, Grady D. Informed consent in randomized quality improvement trials: a critical barrier for learning health systems Editorial. JAMA Intern Med. 2014;174:668-70. PMID: 24615554 doi:10.1001/jamainternmed.2013.13297 CrossrefMedlineGoogle Scholar10. Institute of Medicine. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: National Academies Pr; 2011. Google Scholar Author, Article, and Disclosure InformationAffiliations: From the Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota; Veterans Affairs Medical Center, Memphis, Tennessee; and Veterans Affairs Boston Healthcare System, Boston, Massachusetts.Grant Support: By the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development (Washington, DC).Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-1208.Corresponding Author: Frank A. Lederle, MD, Minneapolis Veterans Affairs Health Care System, One Veterans Drive, Minneapolis, MN 55417; e-mail, frank.email protectedgov.Current Author Addresses: Dr. Lederle: Minneapolis Veterans Affairs Health Care System, One Veterans Drive, Minneapolis, MN 55417.Dr. Cushman: Memphis Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104.Drs. Ferguson, Brophy, and Fiore: Massachusetts Veterans Epidemiology Research and Information Center, Veterans Affairs Boston Healthcare System, 150 South Huntington Avenue, Boston, MA 02130.Author Contributions: Conception and design: F.A. Lederle, W.C. Cushman, R.E. Ferguson, M.T. Brophy, L.D. Fiore.Analysis and interpretation of the data: F.A. Lederle.Drafting of the article: F.A. Lederle, R.E. Ferguson.Critical revision of the article for important intellectual content: F.A. Lederle, W.C. Cushman, R.E. Ferguson, M.T. Brophy.Final approval of the article: F.A. Lederle, W.C. Cushman, R.E. Ferguson, M.T. Brophy, L.D. Fiore.Statistical expertise: R.E. Ferguson.Obtaining of funding: F.A. Lederle, R.E. Ferguson, M.T. Brophy, L.D. Fiore.Administrative, technical, or logistic support: R.E. Ferguson, L.D. Fiore.Collection and assembly of data: F.A. Lederle.This article was published at www.annals.org on 16 August 2016. 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