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Half a Century of Hydrochlorothiazide: Facts, Fads, Fiction, and Follies

      Abstract

      Hydrochlorothiazide (HCTZ) has become by far the most commonly prescribed antihypertensive drug in the US. In 2008, 47.8 million prescriptions were written for HCTZ alone and 87.1 million prescriptions for HCTZ combinations. However, there is no evidence that HCTZ in its usual dose of 12.5-25 mg daily reduces myocardial infarction, stroke, or death. In a meta-analysis of 19 randomized trials with over 1400 patients, the 24-hour decrease in blood pressure with HCTZ was inferior to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and calcium channel blockers (P <.001 for all). Even in combination with an angiotensin-converting enzyme inhibitor, HCTZ was found to reduce morbidity and mortality less well than a calcium channel blocker. As measured by the adherence rate, thiazides are less well tolerated than any other drug class. Because outcome data at the usual daily dose of 12.5-25 mg are lacking, antihypertensive efficacy is paltry, and adherence is poor, HCTZ is an inappropriate first-line drug in hypertension. If a “thiazide-type” diuretic is indicated, either chlorthalidone or indapamide should be selected.
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      References

      1. IMS Health, National Prescription Audit Plus, Year 2008.
        ([database on the Internet]) (Accessed March 2009)
        • Messerli F.H.
        • Makani H.
        • Benjo A.
        • et al.
        Antihypertensive efficacy of hydrochlorothiazide as evaluated by ambulatory blood pressure monitoring: a meta-analysis of randomized trials.
        J Am Coll Cardiol. 2011; 57: 590-600
        • Chobanian A.V.
        • Bakris G.L.
        • Black H.R.
        • et al.
        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: 2560-2572
        • Poblete P.F.
        • Kyle M.C.
        • Pipberger H.V.
        • Freis E.D.
        Effect of treatment on morbidity in hypertension. Veterans Administration Cooperative Study on Antihypertensive Agents. Effect on the electrocardiogram.
        Circulation. 1973; 48: 481-490
      2. Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party.
        BMJ. 1992; 304: 405-412
        • MRC trial of treatment of mild hypertension: principal results. Medical Research Council Working Party
        Br Med J (Clin Res Ed). 1985; 291: 97-104
        • Amery A.
        • De Schaepdryver A.
        The European Working Party on High Blood Pressure in the Elderly.
        Am J Med. 1991; 90: 1S-4S
        • Wing L.M.
        • Reid C.M.
        • Ryan P.
        • et al.
        A comparison of outcomes with angiotensin-converting enzyme inhibitors and diuretics for hypertension in the elderly.
        N Engl J Med. 2003; 348: 583-592
        • Nissen S.E.
        • Tuzcu E.M.
        • Libby P.
        • et al.
        Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial.
        JAMA. 2004; 292: 2217-2225
        • Siscovick D.S.
        • Raghunathan T.E.
        • Psaty B.M.
        • et al.
        Diuretic therapy for hypertension and the risk of primary cardiac arrest.
        N Engl J Med. 1994; 330: 1852-1857
      3. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group.
        JAMA. 1991; 265: 3255-3264
        • ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group
        The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
        JAMA. 2002; 288: 2981-2997
        • Beckett N.S.
        • Peters R.
        • Fletcher A.E.
        • et al.
        Treatment of hypertension in patients 80 years of age or older.
        N Engl J Med. 2008; 358: 1887-1898
      4. Mortality after 10 1/2 years for hypertensive participants in the Multiple Risk Factor Intervention Trial.
        Circulation. 1990; 82: 1616-1628
        • Dorsch M.P.
        • Gillespie B.W.
        • Erickson S.R.
        • et al.
        Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis.
        Hypertension. 2011; 57: 689-694
        • Woodman R.
        • Brown C.
        • Lockette W.
        Chlorthalidone decreases platelet aggregation and vascular permeability and promotes angiogenesis.
        Hypertension. 2010; 56: 463-470
        • Jamerson K.
        • Weber M.A.
        • Bakris G.L.
        • et al.
        Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients.
        N Engl J Med. 2008; 359: 2417-2428
        • Messerli F.H.
        • Bangalore S.
        • Julius S.
        Risk/benefit assessment of beta-blockers and diuretics precludes their use for first-line therapy in hypertension.
        Circulation. 2008; 117 (discussion 2715): 2706-2715
        • Kronish I.M.
        • Woodward M.
        • Sergie Z.
        • et al.
        Meta-analysis: impact of drug class on adherence to antihypertensives.
        Circulation. 2011; 123: 1611-1621
        • Mancia G.
        • Seravalle G.
        • Grassi G.
        Tolerability and treatment compliance with angiotensin II receptor antagonists.
        Am J Hypertens. 2003; 16: 1066-1073
        • Stafford R.S.
        • Bartholomew L.K.
        • Cushman W.C.
        • et al.
        Impact of the ALLHAT/JNC7 Dissemination Project on thiazide-type diuretic use.
        Arch Intern Med. 2010; 170: 851-858
        • Ho P.M.
        • Zeng C.
        • Tavel H.M.
        • et al.
        Trends in first-line therapy for hypertension in the Cardiovascular Research Network Hypertension Registry, 2002-2007.
        Arch Intern Med. 2010; 170: 912-913
        • Ernst M.E.
        • Lund B.C.
        Renewed interest in chlorthalidone: evidence from the veterans health administration.
        J Clin Hypertens (Greenwich). 2010; 12: 927-934

      Linked Article

      • A Reappraisal of Chlorthalidone Also Is Required
        The American Journal of MedicineVol. 125Issue 6
        • Preview
          Although the authors proposed the choice of chlorthalidone as one of the preferred “thiazide-type” diuretics in hypertension,1 the alternative view is that potential adverse effects of thiazide diuretics, including chlorthalidone, favor the use of an angiotensin-converting enzyme inhibitor of angiotensin receptor blocker+a dihydropyridine calcium channel blocker in high-risk patients who require more than 1 antihypertensive drug to control blood pressure.2
        • Full-Text
        • PDF
      • Can Selection Bias in Trials Allow Hydrochlorothiazide to Be Banned?
        The American Journal of MedicineVol. 125Issue 6
        • Preview
          Messerli and Bangalore stated that “there is no evidence that hydrochlorothiazide (HCTZ) in its usual dose of 12.5-25 mg daily reduces myocardial infarction, stroke or death,” but they failed to provide a systematic analysis of the data.1 This contrasts with a review of randomized trials of at least 1 year duration comparing one of 6 major drug classes with placebo or no treatment, including at least 70% of participants with blood pressure>140/90 mm Hg at baseline.2 Of 57 trials identified, 24 trials with 28 arms (n=58,040) met the inclusion criteria.
        • Full-Text
        • PDF