Comparing clinical effectiveness and drug toxicity with hydrochlorothiazide and chlorthalidone using two potency ratios in a managed care population.

This study compared the clinical effectiveness and drug toxicity of chlorthalidone and hydrochlorothiazide. Electronic health records and claims data were used to identify patients initially prescribed chlorthalidone or hydrochlorothiazide. A total of 214 patients prescribed chlorthalidone 25 mg were matched with 428 patients prescribed hydrochlorothiazide 25 mg (1:1 potency ratio) and 214 patients prescribed hydrochlorothiazide 50 mg (1:2 potency ratio). Mean systolic blood pressure/diastolic blood pressure values at least 30 days after initial prescription were lower with chlorthalidone (132.2/74 mm Hg) compared with hydrochlorothiazide 25 mg (137.0/77.5 mm Hg) and hydrochlorothiazide 50 mg (138.6/78.5 mm Hg) (P<.05 for all comparisons). Goal systolic blood pressure/diastolic blood pressure values were achieved in a higher percentage of patients prescribed chlorthalidone (45.0%/78.3%) than with either hydrochlorothiazide 25 mg (32.1%/63.9%) or hydrochlorothiazide 50 mg (32.8%/68.9%) (P<.05 for all comparisons). Mean serum potassium was 3.94 mEq/L with chlorthalidone 25 mg, 4.13 mEq/L with hydrochlorothiazide 25 mg (P<.01 vs chlorthalidone), and 3.96 mEq/L with hydrochlorothiazide 50 mg. These findings indicate that chlorthalidone 25 mg is associated with a better antihypertensive response than hydrochlorothiazide 25 mg or 50 mg, without clinically significant differences in serum potassium.

Should chlorthalidone be the diuretic of choice for antihypertensive therapy?

For decades, diuretic therapy has been a cornerstone in treating hypertension, an approach supported by multiple randomized controlled trials demonstrating reduced morbidity and mortality from cardiovascular events. Yet controversy persists regarding the potential detrimental metabolic effects and side effects of diuretic agents. Within the risk-benefit debates about diuretic therapy is a second dialogue regarding the best thiazide or thiazidelike agent to prescribe. Proponents of chlorthalidone emphasize the demonstrated reductions in cardiovascular events reported from multiple classic trials and its longer half-life, whereas opponents point to its limited availability in low-dose forms and comparable favorable results from hydrochlorothiazide-based therapy to discredit claims of superiority. This review presents the data available on both sides of this issue to help the reader decide which claims are most valid, and offers recommendations for treatment.

Assessment of a fixed-dosage combination of atenolol and chlorthalidone (Tenoretic) in hypertensive Nigerians.

The antihypertensive effect of a fixed dosage combination of the cardioselective beta-adrenoceptor blocker, atenolol, and the oral thiazide-like diuretic, chlorthalidone (Tenoretic) was studied in 24 hypertensive Nigerians in a double-blind, cross-over comparison with three other treatments. These were atenolol alone, 100 mg daily, chlorthalidone alone, 25 mg daily, and atenolol (100 mg) plus chlorthalidone (25 mg) daily taken as separate formulations. Tenoretic was taken as a once-daily tablet containing 100 mg atenolol plus 25 mg chlorthalidone. The order of administration of the drugs was randomized. Each drug was taken for 4 weeks. The results showed that atenolol and chlorthalidone lowered blood pressure to the same extent. Combination of the two drugs whether taken separately or in fixed-dosage combination was better than either product singly. The drugs were well tolerated.

A pharmacokinetic and pharmacodynamic assessment of a combined slow-release metoprolol-chlorthalidone preparation.

Beta adrenoceptor blocking drugs and diuretics are frequently given together to control hypertension and increasingly the two agents are being combined in a single preparation. Possible interactions between the two agents are therefore of interest. In this study the addition of chlorthalidone has been shown not to influence the plasma levels or beta-blocking action of a sustained release form of metoprolol. In addition, when the combination product containing sustained release metoprolol and chlorthalidone is given over 21 days, the plasma levels of each drug are similar to those reported for each drug when given alone.