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How do hydrochlorothiazide and chlorthalidone compare for treating hypertension?

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The 2 groups showed no significant difference in cardiovascular events (3.2 events per 100 person-years for chlorthalidone compared with 3.4 for HCTZ; adjusted hazard ratio [aHR]=0.93; 95% CI, 0.81-1.06).

Serious hypokalemia and hyponatremia are risks

Patients taking chlorthalidone were more likely to be hospitalized for hypokalemia (0.69 per 100 person-years vs 0.27 for HCTZ; aHR=3.1; 95% CI, 2.0-4.6; number needed to harm [NNH]=238 in 1 year) or hyponatremia (0.69 per 100 person-years vs 0.49 for HCTZ; aHR=1.7; 95% CI, 1.2-2.3; NNH=434 in 1 year).2 However, the all-cause hospitalization rates for the 2 drugs were the same (aHR=1.0; 95% CI, 0.93-1.07).

Chlorthalidone may reduce the risk of cardiovascular events in patients with hypertension more than HCTZ.

Lower systolic BP and serum potassium found with chlorthalidone

A smaller retrospective cohort analysis (6441 participants who received either chlorthalidone or HCTZ starting at 50 mg and stepped once to 100 mg) also assessed the difference in cardiovascular events between patients taking the 2 drugs.3 (Cardiovascular events were defined as pooled MIs, onset of angina or peripheral artery occlusive disease, or need for coronary artery bypass.) Although significant reductions in pooled events occurred in both groups over the 7-year study, these reductions were significantly lower in the chlorthalidone group than in the HCTZ group (aHR=0.79; 95% CI, 0.68-0.92).

Systolic blood pressures were statistically lower in the chlorthalidone group during Years 1 through 5 but not in Years 6 and 7 (difference 2-4 mm Hg). Serum potassium was also lower in patients taking chlorthalidone (3.8 mEq/L on chlorthalidone vs 4.0 mEq/L on HCTZ after 7 years; P<.05).

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