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


      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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      Linked Article

      • A Reappraisal of Chlorthalidone Also Is Required
        The American Journal of MedicineVol. 125Issue 6
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          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
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      • 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.
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