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October 20, 2004

Chlorthalidone vs Other Low-Dose Diuretics—Reply

Author Affiliations

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

JAMA. 2004;292(15):1816-1817. doi:10.1001/jama.292.15.1817-a

In Reply: We agree with Dr Choi and colleagues that direct comparisons within active control clinical trials are the optimal method of assessing differences between drugs. When the absence of active control data makes the use of indirect comparisons necessary, it is important to compare things that are similar.

Their reference to MRFIT1 is surprising on several counts. First, they make an indirect comparison between hydrochlorothiazide and chlorthalidone even though the choice between the 2 diuretics was a local option and not a part of the randomized design. Second, for the randomized comparison between special intervention and usual care, MRFIT, which did not use a factorial design, has not generally been included in meta-analyses of hypertension trials2 because the effects of antihypertensive treatment cannot be separated from the effects of the MRFIT nutrition and smoking interventions. Finally, high-dose diuretics were used in MRFIT. These differ from low-dose diuretics in their effects on CHD2,3 and are generally no longer used or recommended in clinical practice. For these reasons, our meta-analysis focused only on trials that evaluated low-dose diuretic therapies. Both ALLHAT and the Second Australian National Blood Pressure Trial did use low-dose diuretic therapies.4,5 ALLHAT included a large proportion of African Americans. Among European Americans in ALLHAT, the differences in outcomes between lisinopril and chlorthalidone were minor.4

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