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Chlortalidone (chlorthalidone) is chemically unrelated to the thiazide diuretics but shares many of their actions and adverse effects.
It is so closely similar to the thiazide diuretics in most respects that data have generally been regarded as interchangeable.
In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), over 40 000 participants aged 55 years or older with hypertension and at least one other risk factor for coronary heart disease were randomized to chlortalidone, amlodipine, doxazosin, or lisinopril [ , ]. Doxazosin was discontinued prematurely because chlortalidone was clearly superior in preventing cardiovascular events, particularly heart failure [ ]. Otherwise, mean follow-up was 4.9 years. There were no differences between chlortalidone, amlodipine, and lisinopril in the primary combined outcome or all-cause mortality. Compared with chlortalidone, heart failure was more common with amlodipine and lisinopril, and chlortalidone was better than lisinopril at preventing stroke.
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