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Blood pressure lowering efficacy of diuretics as second-line therapy for primary hypertension.

BACKGROUND
Diuretics are widely prescribed for hypertension not only as a first-line drug but also as a second-line drug. Therefore, it is essential to determine the effects of diuretics on blood pressure (BP), heart rate and withdrawals due to adverse effects (WDAEs) when given as a second-line drug.


OBJECTIVES
To quantify the additional reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) of diuretic therapy as a second-line drug in patients with primary hypertension


SEARCH STRATEGY
CENTRAL (The Cochrane Library 2008, Issue 2), MEDLINE (1966-July 2008), EMBASE (1988-July 2008) and bibliographic citations of articles and reviews were searched.


SELECTION CRITERIA
Double-blind, randomized, controlled trials evaluating the BP lowering efficacy of a diuretic in combination therapy with another class of anti-hypertensive drugs compared with the respective monotherapy (without a diuretic) for a duration of 3 to 12 weeks in patients with primary hypertension.


DATA COLLECTION AND ANALYSIS
Two review authors independently extracted the data and assessed trial quality.


MAIN 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 caused 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 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. These RCTs showed a BP lowering effect of a starting dose of about 6/3 mmHg.


AUTHORS' CONCLUSIONS
Thiazides when given as a second-line drug have a dose related effect to lower blood pressure that is similar to when they are added as a first-line drug. This means that the BP lowering effect of thiazides is additive. Loop diuretics appear to have a similar blood pressure lowering effect as thiazides at 1 times the recommended starting dose. Because of the short duration of the trials and lack of reporting of adverse events, this review does not provide a good estimate of the incidence of adverse effects of diuretics given as a second-line drug.