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To the Editor: In the Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial,¹ the first-line therapy in the low-dose diuretic arm was chlorthalidone. Some recent trials of low-dose diuretics, however, have used other treatments such as indapamide and hydrochlorothiazide, sometimes in combination with triamterene or amiloride.^2-3 Although chlorthalidone is about 1.5 to 2.0 times more potent and has a much longer duration of action than hydrocholorthiazide,⁴ it remains unknown whether different diuretics are associated with different clinical outcomes.

Methods
Using data from our network meta-analysis,⁵ we divided placebo-controlled trials of low-dose diuretics into those that used chlorthalidone (n = 2)^6-8 and those that used other low-dose diuretic therapies (n = 3)^2-3,9 (Table 1). We used fixed-effects techniques for the comparison of 6 clinical outcomes, including coronary heart disease (CHD) events, heart failure, stroke, cardiovascular disease (CVD) events, CVD mortality, and total mortality. We first computed the relative risk of the 2 types of diuretics against placebo, and then computed the ratio of the 2 relative risks in order to obtain an indirect estimate of the effect of chlorthalidone vs other diuretics.⁵

View this table: [in this window] [in a new window] Table. Direct and Indirect Comparisons of Low-Dose Diuretics: Chlorthalidone and Nonchlorthalidone Treatments for 6 Outcomes Based on Placebo-Controlled Trials

Results
These 5 trials included 214 CHD events and 660 deaths among the 7146 participants randomized to receive low-dose diuretic therapy and another 370 CHD events and 871 deaths among the 7940 randomized to receive placebo. Although there were no data available for heart failure in the nonchlorthalidone group, each of the other 5 pairs of estimates for the 2 types of low-dose diuretic therapies were similar. The indirect comparisons and their 95% confidence intervals suggest that large differences between them are not likely (Table 1).

Comment
Based on the available data from the placebo-controlled trials evaluating low-dose diuretics, major health outcomes for chlorthalidone and other thiazide-like drugs appear to be similar.

Bruce M. Psaty, MD, PhD
psaty{at}u.washington.edu

Thomas Lumley, PhD
Cardiovascular Health Research Unit
University of Washington
Seattle

Curt D. Furberg, MD, PhD
Department of Public Health Sciences
Wake Forest University
Winston-Salem, NC

1. 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;288:2981-2997. FREE FULL TEXT 2. Amery A, Birkenhager W, Brixko P, et al. Mortality and morbidity from the European Working Party on High Blood Pressure in the Elderly trial. Lancet. 1985;1:1349-1354. ISI | PUBMED 3. Medical Research Council Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ. 1992;304:405-412. ISI | PUBMED 4. Carter BL, Ernst ME, Cohen JD. Hydrochlorothiazide versus chlorthalidone. Hypertension. 2004;43:4-9. FREE FULL TEXT 5. Psaty BM, Lumley T, Furberg CD, et al. Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis. JAMA. 2003;289:2534-2544. FREE FULL TEXT 6. Perry MH Jr, Smith WM, McDonald RH, et al. Morbidity and mortality in the Systolic Hypertension in the Elderly Program (SHEP) pilot study. Stroke. 1989;20:4-13. FREE FULL TEXT 7. SHEP Cooperative Research Group. 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). JAMA. 1991;265:3255-3264. ABSTRACT 8. Kostis JB, Davis BR, Cutler J, et al. Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. JAMA. 1997;278:212-216. ABSTRACT 9. PATS Collaborating Group. Post-Stroke Antihypertensive Treatment Study: a preliminary report. Chin Med J (Engl). 1995;108:710-717.

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2004;292:43-44.

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