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A systematic review of the blood pressure lowering efficacy of diuretics as second-line therapy for primary hypertension Chen, Mei Hui


Context: Although other factors independent of their blood pressure (BP) lowering effect may contribute to the reduction in morbidity and mortality associated with antihypertensive drugs, efficacy of an antihypertensive treatment is gauged by the magnitude of BP reduction. Diuretics are widely prescribed for hypertension not only as first-line monotherapy but also second-line in combination therapy. Therefore, it is essential to determine the effects of diuretics on BP, heart rate (HR) and withdrawals due to adverse effects (WDAEs) when used second-line for hypertension. Objectives: 1) To quantify the additional BP reduction of a diuretic as a second-line drug in combination therapy in patients with primary hypertension (systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg); 2) To determine the additional effects on HR and WDAEs. Methods: A systematic review of published, double-blind, randomized controlled trials (RCTs) evaluating the BP lowering efficacy of combination therapy (with a diuretic) compared with the respective monotherapy (without a diuretic) for a duration of 3 to 12 weeks in patients with primary hypertension was conducted. Electronic databases were searched for the relevant trials and data were analyzed using Review Manager 5.0.20. Results: Fifty-three double-blind RCTs evaluating a thiazide in 15129 hypertensive patients (baseline BP of 156/101 mmHg) were included. Hydrochlorothiazide was the thiazide used in 49/53 (92%) of the included studies. The additional BP reduction induced by the thiazide as a second drug was estimated by comparing the difference in BP reduction between the combination and monotherapy groups. Thiazides as a second-line drug reduced BP reduction by 6/3 and 8/4 mmHg at doses of 1 and 2 times the manufacturer's recommended starting dose respectively. The BP lowering effect was dose related. The effect was similar to that obtained when thiazides are used as a single agent. Only 3 double-blind RCTs evaluating loop diuretics were identified; however, at one times the manufacturer’s recommended dose, the BP lowering effect is similar to thiazides. Conclusion: Thiazides when given as a second-line drug have a dose related effect to lower blood pressure that is similar to when they are used as a first-line drug.

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