A Cochrane review [Abstract] 1 included 53 studies with a total of 15 129 hypertensive patients (baseline BP of 156/101 mmHg). Hydrochlorothiazide was the thiazide used in 92% of the included studies. Adding a thiazide to another anti-hypertensive drug further reduced the systolic blood pressure (SBP) by an additional of -6.0 mmHg (95% CI -6.5 to -5.4; 32 studies, n= 8482) and diastolic blood pressure (DBP) by an additional of -3.1 mmHg (95% CI -3.4 to -2.8; 35 studies, n= 8804) when given at the starting dose. The corresponding reductions were -8.0 mmHg (95% CI -8.7 to -7.3; 25 studies, n=6079) in SBP and -4.1 mmHg (95% CI -4.4. to -3.6; 29 studies, n=6572) in DBP when given at 2 times the starting dose. The BP lowering effect was dose related. The effect was similar to that obtained when thiazides are used as a single agent.
Adding a loop diuretic as a second drug was effective starting at 1x the manufacturer's recommended dose, resulting in an additional reduction of -6.5 mmHg (95% CI -9.0 to -4.0; 2 studies, n=629) in SBP and -3.1 mmHg (95% CI -4.5 to -1.7) in DBP.
A good estimate of the harms associated with diuretics could not be estimated because of the lack of reporting and the short duration of the trials. Adding a thiazide as a second-line drug did not result in a significant increase or reduction in withdrawals due to adverse effects (RR 1.09, 95% CI 0.84 to 1.42; 35 studies, n=9258). Adding a loop diuretic as the second drug was not shown to have any significant impact on the number of withdrawals due to adverse effects (2 studies).
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment and blinding).
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