Diuretics are first choice for hypertension

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  • BACKGROUND: Hypertension is common in family practice, but controversy remains about which medication should be used first. This network meta-analysis compares the efficacy of 6 common classes of antihypertensive agents: diuretics, beta-blockers, calcium-channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and alpha-blockers.
  • POPUL ATION STUDIED: This study identified 42 trials with 192,478 patients in many countries, including the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT) study and the Australian National Blood Pressure Study. Some studies included patients with renal disease, diabetes, or existing cardiovascular disease, but those recruiting patients with congestive heart failure or prior myocardial infarction were excluded.
  • STUDY DESIGN AND VALIDITY: Network meta-analysis is a novel methodology that combines direct evaluation of a treatment through traditional meta-analysis with indirect evaluation through comparing effects across trials that share a third treatment in common. Thus, if trial X compares treatments A and B, and trial Y compares treatments B and C, an indirect approach allows comparison of A and C. A network approach is very appropriate for studies of antihypertensives, which represent a patchwork of clinical trials for many different agents.
  • OUTCOMES MEASURED: The primary outcomes measured were coronary heart disease events, congestive heart failure, stroke, total cardiovascular events, cardiovascular mortality, and total mortality. Side effects, cost, quality of life, and patient satisfaction were not addressed.
  • RESULTS: Low levels of incoherence were present for all comparisons. Diuretics decreased all measured outcomes, including cardiovascular disease events (relative risk [RR]= 0.79; 95% confidence interval [CI], 0.69–0.92), congestive heart failure (RR=0.51; 95% CI, 0.42–0.62), stroke (RR=0.71; 95% CI, 0.63–0.81), and total mortality (RR=0.90; 95% CI, 0.84–0.96).



Low-dose diuretics are equal or superior to all other major classes of antihypertensive medications in improving long-term cardiovascular outcomes. Given that diuretics are also inexpensive and have a favorable side-effect profile, clinicians should use low-dose diuretics (eg, hydrochlorothiazide 25 mg/d or less) as a first choice for almost all patients with hypertension.

Clinicians should keep in mind that many patients require more than 1 medication. They should look for further information from pooled studies regarding specific populations such as those with diabetes or chronic renal disease, the elderly, or persons of color.

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