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Use a Thiazide Diuretic First for Hypertension

The ALLHAT hypertensive-study results are in, and the practice implications are clear.

ACE inhibitors (ACEIs) and calcium-channel blockers (CCBs) are superior to placebo for preventing adverse cardiovascular events, but how effective are they relative to diuretics? In the ALLHAT randomized study, researchers compared 3 antihypertensive agents -- a CCB (amlodipine; 2.5-10 mg/day), an ACEI (lisinopril; 10-40 mg/day), and an alpha-blocker (doxazosin) -- with standard diuretic treatment (chlorthalidone; 12.5-25 mg/day) in hypertensive patients aged 55 and older. The doxazosin arm was halted early because of increased adverse events (Journal Watch Cardiology Jun 16 2000), leaving 33,357 subjects (47% female; 32% black) in the other 3 arms.

At a mean follow-up of 5 years, systolic blood pressure was significantly higher among amlodipine recipients (by about 1 mm Hg) and lisinopril recipients (by about 2 mm Hg) than among chlorthalidone recipients. All-cause mortality rates did not differ significantly among the 3 groups, nor did rates of the primary composite outcome (fatal coronary heart disease or nonfatal MI). However, some secondary outcomes were worse with the CCB and the ACEI than with the diuretic. For example, compared with chlorthalidone recipients, amlodipine and lisinopril recipients each had significantly higher heart-failure rates, and lisinopril recipients experienced significantly more total adverse cardiovascular events.

Comment: In ALLHAT, standard diuretic therapy with chlorthalidone achieved similar primary outcomes, and somewhat better secondary outcomes, compared with amlodipine and lisinopril. Considering the better secondary outcomes with the diuretic and its lower cost, an editorialist urges that thiazide diuretics be considered the preferred initial therapy for hypertension. Given that this study shows that diuretics and ACE inhibitors are comparable first-line therapies for hypertension, the findings should be incorporated into future clinical-practice guidelines.

— JoAnne M. Foody, MD

Published in Journal Watch Cardiology January 31, 2003

Citation(s):

The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. 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 Dec 18; 288:2981-97.

• Original article (Subscription may be required)
• Medline abstract (Free)

Appel LJ. The verdict from ALLHAT -- Thiazide diuretics are the preferred initial therapy for hypertension. JAMA 2002 Dec 18; 288:3039-42.

• Original article (Subscription may be required)
• Medline abstract (Free)