The certainty of evidence is downgraded by study limitations (lack of allocation concealment and selective outcome reporting), by imprecise results (wide confidence intervals), and by indirectness (no data on participants with other risk factors of myocardial infarction and strokes).
A Cochrane review [Abstract] 1 included 27 studies, and the quantitative analysis included 25 studies with a total of 3 016 subjects with primary hypertension. All studies excluded people with risk factors of myocardial infarction and strokes. The studies compared once-daily administration of monotherapy antihypertensive drug (angiotensin-converting enzyme inhibitors (ACEIs) in 6 studies, calcium channel blockers (CCBs) in 9 studies, angiotensin II receptor blockers (ARBs) in 7 studies, diuretics in 2 studies, alpha-blockers in 1 study, and beta-blockers in 1 study) at night (6 p.m. to midnight) or in the morning (6 a.m. to noon).
No difference between evening versus morning dosing was observed in all-cause mortality after 26 weeks of active treatment (RR 0.49, 95% CI 0.04 to 5.42; 1 study, n=735), serious adverse events after 8 to 26 weeks of active treatment (RR 1.17, 95% CI 0.53 to 2.57; 2 studies, n=833), overall adverse events after 6 to 26 weeks of active treatment (RR 0.89, 95% CI 0.67 to 1.20; 7 studies, n=1 541) and withdrawals due to adverse events after 6 to 26 weeks of active treatment (RR 0.76, 95% CI 0.47 to 1.23; 7 studies, n=1 777).
Evening dosing slightly reduced 24-hour mean systolic blood pressure (SBP -1.34 mmHg, 95% CI -2.38 to -0.30 mmHg; statistical heterogeneity I2 =87%; 25 studies, n=3 073) and 24-hour mean diastolic blood pressure (DPB -1.01 mmHg, 95% CI -1.75 to -0.27 mmHg, statistical heterogeneity I2 =88%; 25 studies, n=3 073) compared to morning dosing.
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