Summary of findings for the main comparison. Dose‐ranging blood pressure‐lowering efficacy of hydrochlorothiazide for primary hypertension.
| Hydrochlorothiazide compared with placebo for primary hypertension | |||||
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Patient or population: adults with primary hypertension Settings: outpatient Intervention: hydrochlorothiazide 3 to 100 mg/day Comparison: placebo | |||||
| Outcomes | Daily dose | MD (95% CI) mmHg | No of participants (studies) | Quality of the evidence (GRADE) | Comments |
| Systolic blood pressure | 3 to 6.25 mg | ‐3.6 (‐5.6 to ‐1.5) | 663 (8) | ⊕⊕⊕⊝ moderate1 |
Similar to the effect as a second‐line drug (Chen 2009). This is an indirect comparison of the effect size with a wider confidence interval compared to the Chen review, which is based on 22 trials in 3283 patients using similar inclusion/exclusion criteria with systolic blood pressure‐lowering of ‐3.7 (‐4.6 to ‐2.8) mmHg |
| 12.5 mg | ‐6.3 (‐7.2 to ‐5.3) | 2645 (22) | ⊕⊕⊕⊕ high | A narrow confidence interval based on a large sample size with a magnitude of lowering very similar to the effect as a second‐line drug (Chen 2009), which was ‐6.0 (‐6.5 to ‐5.4) mmHg | |
| 25 mg | ‐8.0 (‐9.0 to ‐7.0) | 3062 (25) | ⊕⊕⊕⊕ high | A narrow confidence interval based on a large sample size with a magnitude of lowering very similar to the effect as a second‐line drug (Chen 2009), which was ‐8.0 (‐8.7 to ‐7.3) mmHg | |
| 50 to 100 mg | ‐10.2 (‐13.1 to ‐7.3) | 315 (2) | ⊕⊕⊝⊝ low1 | The 2 included studies have a high risk of bias. The confidence interval is very wide with small a sample size providing insufficient data in both this review as well as in the Chen review comparing the effect as a second‐line drug (Chen 2009) | |
| Diastolic blood pressure | 3 to 6.25 mg | ‐2.4 (‐3.7 to ‐1.2) | 662 (8) | ⊕⊕⊕⊝ moderate1 |
Similar to the effect as a second‐line drug (Chen 2009). This is an indirect comparison of the effect size with a wider confidence interval compared to the Chen review, which is based on 23 trials in 3364 patients using similar inclusion/exclusion criteria, with diastolic blood pressure‐lowering of ‐1.7 (‐2.2 to ‐1.2) mmHg. |
| 12.5 mg | ‐3.1 (‐3.7 to ‐2.5) | 2877 (25) | ⊕⊕⊕⊕ high | Similar to the effect as a second‐line drug (Chen 2009), with a narrow confidence interval based on a large sample size with a magnitude of lowering similar to the effect as a second‐line drug (Chen 2009), which was ‐3.1 (‐3.4 to ‐2.8) mmHg | |
| 25 mg | ‐3.3(‐3.8 to ‐2.8) | 3359 (29) | ⊕⊕⊕⊕ high | Similar to the effect as a second‐line drug (Chen 2009). This is an indirect comparison of the effect size with a wider confidence interval compared to the Chen review, which is based on 42 trials in 6153 patients using similar inclusion/exclusion criteria with diastolic blood pressure‐lowering of ‐4.0 (‐4.4 to ‐3.6) mmHg | |
| 50 to 100 mg | ‐4.7 (‐6.1 to ‐3.3) | 345 (4) | ⊕⊕⊝⊝ low1 | The 4 included studies had a high risk of bias. The confidence interval is very wide with a small sample size providing insufficient data in both this review as well as in the Chen review comparing the effect as a second‐line drug (Chen 2009) | |
| GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate. CI: confidence interval; MD: mean difference | |||||
1Downgraded due to the small number of patients and wide confidence intervals.