Chlorthalidone is better at lowering the risk of a cardiovascular event, such as a heart attack. Early, small dose-equivalence studiesMen and women aged 18 to 79 years were eligible if they had prehypertension or a new or established diagnosis of hypertension (stage 1 or 2), were not receiving antihypertensive medications, and had average office BP values in the last 6 months between 140 and 179 mm Hg systolic or 90 and 109 mm Hg diastolic.Patients were excluded for the following reasons: (1) office BP ≥180/110 mm Hg; (2) use of a thiazide-type diuretic or any other antihypertensive agent within the last 3 months; (3) type 1 or 2 diabetes; (4) chronic renal insufficiency (serum creatinine ≥1.8 mg/dL); (5) pregnancy; (6) dementia or other cognitive impairment prohibiting informed consent; (7) history of ischemic stroke, unstable angina, or myocardial infarction within the past 6 months; (8) chronic use of decongestants, other sympathomimetic agents, or nonsteroidal antiinflammatory drugs; (9) documented alcoholism or current illicit drug use; (10) chronic atrial fibrillation; (11) history of gout or hyperuricemia; or, (12) known allergy to study medications.The study was a randomized, single-blinded, 8-week active treatment, crossover trial with a 4-week washout between treatments.Patients were identified at a regular clinic visit from 2 primary care practices (1 internal medicine and 1 family medicine) within the University of Iowa Family Care Center.
0000003466 00000 n 0000002575 00000 n Though chemically related to the sulfonamides, Pharmacokinetic differences are often responsible for differences in clinical effects within a given drug class. All of the study procedures were approved by the University of Iowa Institutional Review Board, University of Iowa Hospitals and Clinics Pharmacy and Therapeutics Review Board, and University of Iowa Hospitals and Clinics General Clinical Research Center Review Board.Patients were randomized to receive either HCTZ (Qualitest Pharmaceuticals Inc) or chlorthalidone (Mylan Pharmaceuticals Inc). 0000019612 00000 n 0000058373 00000 n In addition, because ABPM was not performed at week 4, the week-8 responses do not fully represent response to forced-dose titration but are a response to 8 weeks of total therapy. We conducted a randomized, single-blinded, 8-week active treatment, crossover study comparing chlorthalidone 12.5 mg/day (force-titrated to 25 mg/day) and hydrochlorothiazide 25 mg/day (force-titrated to 50 mg/day) in untreated hypertensive patients. 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. 0000009766 00000 n
Blood pressure is only a predictor of cardiovascular risk. 0000022696 00000 n

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In their network metaanalysis, Psaty and FurbergOur study compared the antihypertensive efficacy of usual recommended doses of HCTZ and chlorthalidone using both ABPM and conventional sphygmomanometry. Despite these beliefs, there is some suggestion that cardiovascular outcomes are not necessarily the same with these 2 drugs. Chlorthalidone and indapamide, both thiazide-like diuretics, have been shown to provide greater antihypertensive efficacy and, more importantly, to reduce cardiovascular events and mortality compared with hydrochlorothiazide (a thiazide-type diuretic) . Although it is possible that these differences are related to the population demographics, it is equally possible that cited differences account for the differences in outcome. Visit cvs.com for more details. Thirty patients completed the first active treatment period, whereas 24 patients completed both. Had we been able to use data from both active treatment periods with no carryover effect, it is likely that these tests for group differences would have resulted in smaller Third, we compared only 2 commonly used doses of each drug.

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