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A systematic review of the blood pressure lowering efficacy of thiazide and loop diuretics in the treatment of primary hypertension Musini, Vijaya Manavendra


Context- First-line treatment of hypertension with low- or high-dose thiazide therapy compared to placebo or untreated control group reduced blood pressure to a similar extent but their effect on mortality or coronary events appeared to be different. Objectives.- To determine the dose-related decrease in systolic and diastolic blood pressure, withdrawal due to adverse drug effects and metabolic adverse effects of thiazide and loop diuretic monotherapy compared to a placebo control, for a duration of 3-12 weeks, in patients with primary hypertension (SBP > 160 and/or DBP > 90 mmHg). Design.- A systematic review of all randomised placebo controlled trials. Setting.- Electronic databases were searched using the standard search strategy of the Cochrane Hypertension Review group. Data were analysed using Review Manager 4.0. Participants.- 33 trials, involving 4,811 patients reported data on thiazides and only 3 trials involving 150 patients reported data on loop diuretics. Results.- BP lowering efficacy: The dose of thiazide approaching near maximal systolic and diastolic blood pressure lowering efficacy with the best overall estimate in mm Hg identified was: hydrochlorothiazide 25 mg/day (9/5); chlorthalidone 12.5 mg/day (10/3) and indapamide 1.0 mg/day (7/4). The overall best estimate for combined doses of all thiazide drugs was 10/4 mm Hg. Lowand high-dose thiazides lowered blood pressure to a similar extent. Evidence relating to loop diuretics is insufficient to determine a dose-related effect on any of the outcome measures. Withdrawal due to adverse drug effects were similar to the placebo group in low and high-dose thiazide trials. The overall relative risk of withdrawal due to adverse events for thiazides was 1.2(0.8, 1.2). Metabolic adverse effects: Combined high doses of all thiazide drugs showed a significant decrease in serum potassium levels as compared to combined lowdoses. A significant decrease in serum potassium and a significant increase in serum uric acid, creatinine, triglyceride and total cholesterol were observed compared to the placebo control group. Conclusion.- The lowest range of clinically used doses of thiazide diuretic showed near maximal blood pressure lowering efficacy and a lower incidence of adverse metabolic effects. It is recommended that there is no advantage to using doses higher than those defined as low dose.

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