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Review: low-dose thiazides are the most effective first-line drugs for hypertension
  1. Mohammad G Saklayen, MD
  1. Wright State University, Centerville, Ohio, USA

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 QUESTION: In patients with hypertension, which first-line drugs are effective for reducing death and cardiovascular events?

    Data sources

    Studies were identified by searching Medline (1966–97), the Cochrane Library (1998 issue 2), and references of previous meta-analyses (1980–97).

    Study selection

    Studies were selected if patients had systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥90 mm Hg; random allocation was used; a first-line antihypertensive drug was compared with another first-line drug or no treatment (including placebo); group baseline characteristics were reported; end points were defined; ≥1-year of follow-up was reported; and >70% of patients were receiving the study drug after 1 year. Studies were excluded if antihypertensive drugs were used for indications other than hypertension.

    Data extraction

    2 reviewers independently extracted data on patients, study duration, treatment, outcomes (death, stroke, coronary artery disease [CAD], and total cardiovascular events), and withdrawals because of adverse effects.

    Main results

    23 studies (50 853 patients) met the inclusion criteria. Sample sizes ranged from 87–17 354 patients. In meta-analyses of drug-drug comparisons, no differences existed in death, stroke, CAD, or total cardiovascular events. Fewer withdrawals because of adverse effects occurred with thiazides than with β-blockers and in 1 trial with a calcium-channel blocker than with an angiotensin-converting enzyme (ACE) inhibitor (table). In comparisons of drugs with no treatment, low-dose thiazides reduced death, and thiazides (all doses) and a calcium-channel blocker reduced stroke and total cardiovascular events; only low-dose thiazides reduced CAD (table).

    Effectiveness of first-line antihypertensive drugs for hypertension at up to 10 years*


    In patients with hypertension, low-dose thiazides are effective for reducing death, stroke, and coronary artery disease.


    Many large studies have shown that low-dose thiazide diuretics are efficacious and efficient in treating hypertension. Several national guidelines, including the US Joint National Committee on the Prevention, Detection, and Evaluation and Treatment of Hypertension,1 have recommended thiazides as first-line antihypertensive therapy. Yet in practice, use of thiazides lags far behind the newer antihypertensive drugs, even though the effectiveness of these has been less well shown.

    Unfortunately, few direct comparisons have been done among different classes of antihypertensive drugs. Those comparisons that have been done were limited to 2 classes of drugs in any 1 study, usually between β-blockers and thiazides. A comparison of several classes of drugs is now under way in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study.2 It is designed to compare the mortality and cardiovascular outcomes of a relatively high-risk group of patients with hypertension treated with either a thiazide, a calcium-channel blocker, an ACE inhibitor, or an α-blocker. This large study with 42 451 patients is partially completed, and final results are expected in 2–3 years.

    What should clinicians do until then? As concluded in this and other systematic reviews (using somewhat different methods), low-dose thiazides should be the first line of treatment for hypertension. Such treatment reduces not only risk for stroke but also other cardiovascular morbidity and mortality. Thiazides are inexpensive drugs with the strongest evidence for effectiveness from hypertension studies.



    • Sources of funding: British Columbia Ministry of Health and the University of British Columbia.

    • For correspondence: Dr J M Wright, Department of Pharmacology and Therapeutics, 2176 Health Sciences Mall, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. FAX 604-822-0701.