Meta-Analysis of Dose-Response Relationships for Hydrochlorothiazide, Chlorthalidone, and Bendroflumethiazide on Blood Pressure, Serum Potassium, and Urate

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 59; no. 6; pp. 1104 - 1109
• Main Authors: Peterzan, Mark A., Hardy, Rebecca, Chaturvedi, Nish, Hughes, Alun D.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.06.2012; Lippincott Williams & Wilkins
• Subjects: Antihypertensive Agents - administration & dosage; Antihypertensive Agents - therapeutic use; Arterial hypertension. Arterial hypotension; Bendroflumethiazide - administration & dosage; Bendroflumethiazide - therapeutic use; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Cardiology. Vascular system; Chlorthalidone - administration & dosage; Chlorthalidone - therapeutic use; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Hydrochlorothiazide - administration & dosage; Hydrochlorothiazide - therapeutic use; Hypertension - blood; Hypertension - drug therapy; Medical sciences; Potassium - blood; Randomized Controlled Trials as Topic; Treatment Outcome; Uric Acid - blood; Hypertension; Benzothiadiazine derivatives; meta-analysis; Cardiovascular disease; Hydrochlorothiazide; Inorganic element; Dose activity relation; Diuretic; Sulfonamides; diuretics; Antihypertensive agent; Arterial pressure; Blood pressure; Thiazide; Bendroflumethiazide; Potassium; Chlortalidone
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.111.190637

Thiazide and thiazide-like diuretics are widely used in the management of hypertension, but recently the equivalence of hydrochlorothiazide and chlorthalidone for blood pressure (BP) lowering and prevention of cardiovascular disease has been questioned. We performed a meta-analysis to characterize the dose-response relationships for 3 commonly prescribed thiazide diuretics, hydrochlorothiazide, chlorthalidone, and bendroflumethiazide, on BP, serum potassium, and urate. Randomized, double-blind, parallel placebo-controlled trials meeting the following criteria, ≥2 different monotherapy dose arms, follow-up duration ≥4 weeks, and baseline washout of medication ≥2 weeks, were identified using Embase (1980–2010 week 50), Medline (1950–2010 November week 3), metaRegister of Controlled Trials, and Cochrane Central. A total of 26 trials examined hydrochlorothiazide, 3 examined chlorthalidone, and 1 examined bendroflumethiazide. Studies included a total of 4683 subjects in >53 comparison arms. Meta-regression of the effect of thiazides on systolic BP showed a log-linear relationship with a potency seriesbendroflumethiazide>chlorthalidone>hydrochlorothiazide. The estimated dose of each drug predicted to reduce systolic BP by 10 mm Hg was 1.4, 8.6, and 26.4 mg, respectively, and there was no evidence of a difference in maximum reduction of systolic BP by high doses of different thiazides. Potency series for diastolic BP, serum potassium, and urate were similar to those seen for systolic BP. Hydrochlorothiazide, chlorthalidone, and bendroflumethiazide have markedly different potency. This may account for differences in the antihypertensive effect between hydrochlorothiazide and chlorthalidone using standard dose ranges.