Chlorthalidone appears better than hydrochlorothiazide for high-risk patients with hypertension
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Chlorthalidone appears to be superior to hydrochlorothiazide for hypertension treatment in high-risk patients, a new study reports.
Researchers at the University of Michigan performed a retrospective observational cohort study using data from the National Heart, Lung and Blood Institute's Multiple Risk Factor Intervention Trial (MRFIT). MRFIT examined primary cardiovascular prevention with chlorthalidone (CTD) or hydrochlorothiazide (HCTZ) in high-risk men (defined as those in the upper 15% of risk for death from coronary heart disease based on elevated cholesterol, elevated diastolic blood pressure and cigarette smoking). Cardiovascular and several laboratory values, including systolic blood pressure, cholesterol, and triglycerides, were measured yearly beginning at study enrollment in 1973. The current trial's primary objective was comparing cardiovascular end points in patients who took CTD and those who took HCTZ. The researchers also compared change in systolic blood pressure; total, low-density lipoprotein and high-density lipoprotein cholesterol; triglycerides; potassium; glucose; and uric acid. The study was published early online March 7 by Hypertension.
The MRFIT included 12,866 patients, of whom 2,392 were initially prescribed CTD and 4,049 were initially prescribed HCTZ. Median follow-up was six years. Seventy-five percent of patients who began the study on HCTZ and 76% of those who began the study on CTD either crossed over to the other drug group or stopped taking diuretics at some point during follow-up. After performing repeated-measures mixed modeling, adjusting each model for predictors of each variable, the authors found that cardiovascular event rates were statistically significantly lower in patients taking CTD or HCTZ (adjusted hazard ratios, 0.51 [95% CI, 0.43 to 0.61] and 0.65 [95% CI, 0.55 to 0.75]) than in those who took neither drug (P<0.0001 for both comparisons). Patients taking CTD had statistically significantly fewer cardiovascular events than those taking HCTZ (P=0.0016). Systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and potassium levels were statistically significantly lower over time in patients taking CTD than in those taking HCTZ, while uric acid levels were statistically significantly higher.
The authors speculated that CTD may work better than HCTZ because of greater potency and longer half-life, and because it may lead to greater reductions in systolic blood pressure. Limitations of the study include its observational design and potential unmeasured confounding, the authors acknowledged. They concluded that both CTD and HCTZ reduce cardiovascular events compared to no treatment in high-risk patients with hypertension, but that CTD is more effective although HCTZ is more commonly prescribed, and that randomized trials are needed for confirmation. The authors of an accompanying editorial agreed, writing that until data from such trials are available, “the totality of the evidence favors the use of chlorthalidone over HCTZ as the preferred diuretic in hypertension treatment.”