Chlorthalidone compared with hydrochlorothiazide in reducing cardiovascular events: systematic review and network meta-analyses. Several studies, however, support once-daily dosing of HCTZ, demonstrating that the pharmacodynamic response is much longer than predicted by the half-life.Chlorthalidone serum concentrations peak ≈2 to 6 hours after oral administration (Chlorthalidone rapidly enters (half-life, 15 minutes) and concentrates in erythrocytes.The natriuretic effect of chlorthalidone was maximal at 18 hours and lasted >48 hours in one early study of the drug.Doses of HCTZ often exceeded 100 mg daily, and the use of 200 to 450 mg daily was not unusual.Five important principles are evident with HCTZ dosing: (1) some patients will respond to doses of 12.5 mg daily, (2) doses >25 mg daily often lower BP only slightly more than does 25 mg (ie, a relatively flat dose response), (3) hypokalemia is dose related, and the risk increases with dose,Early studies with chlorthalidone used doses of 200 to 600 mg daily.Several other studies have confirmed that lower doses of chlorthalidone, especially 12.5 mg and 25 mg daily, offer the best efficacy-to–side effect ratio with respect to hypokalemia.The studies cited earlier give some insight into dose equivalence between HCTZ and chlorthalidone, but none of these studies directly compared the 2 agents. Outpatient and inpatient care episodes of first-time users of antihypertensive monotherapy in the United States based on two administrative claims databases and one collection of electronic health records were analyzed. Oparil S, Doses above 50mg/day are rarely used and may lead to significant hypokalemia
The exposures of interest were use of chlorthalidone and HCTZ. 2 Initial doses were typically either 25 mg chlorthalidone (70% of patients on chlorthalidone) or 12.5 mg HCTZ (67% of patients on HCTZ). Chlorthalidone was associated with a significantly lower risk of diagnosed abnormal weight gain (HR, 0.73; 95% CI, 0.61-0.86). When all study durations were pooled, 12.5 to 25 mg of chlorthalidone produced a statistically greater reduction in systolic blood pressure compared with HCTZ (−24 mm Hg vs… Roush GC, et al. To make fair comparisons, the dose of the diuretic in each arm was assigned 1 of 3 dose levels. Thiazide diuretics have demonstrated favorable blood pressure lowering efficacy, but the equivalent doses of their more common agents, chlorthalidone and hydrochlorothiazide, are still unclear.
This systematic review retrieved 9765 publications, and from these, it identified 14 randomized trials with 883 patients comparing HCTZ with INDAP and chlorthalidone on antihypertensive potency or metabolic effects. The typical starting doses of HCTZ should be 12.5 mg in the elderly and 25 mg in younger patients. Elderly: Initial: 12.5-25 mg/day or every other day; there is little advantage to using doses >25 mg/day . Holford TR, Meta-analysis of dose-response characteristics of hydrochlorothiazide and chlorthalidone: effects on systolic blood pressure and potassium. use prohibited. INDAP has reduced left ventricular mass index by 17% (For reducing cardiovascular events, in the PATS (Post Stroke Antihypertensive Treatment Study) trial, 2.5 mg of INDAP reduced stroke by 29% and all cardiovascular events by 23% versus placebo.Although HCTZ has less than a 24-hour duration of diuretic and antihypertensive action,In spite of greater antihypertensive potency, INDAP did not have a detectably greater effect than HCTZ on metabolic adverse effects. Carter BL, There are significant pharmacokinetic and pharmacodynamic differences between these diuretics. Answers are drawn from an approved set of evidence-based resources and undergo peer review.The complete database of evidence-based questions and answers is copyrighted by FPIN.
A few studies that included combinations with potassium-sparing diuretics were considered secondary sources of data, because several studies demonstrated that neither amiloride nor triamterene added to the antihypertensive effects of HCTZ or chlorthalidone.It is impossible to directly compare trials because of heterogeneous populations.
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