Timing of antihypertensive medication (bedtime versus morning) and cardiovascular risk: an updated systematic review and meta-analysis

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Abstract
Introduction: Previous studies on the optimal timing for antihypertensive medication administration have yielded inconsistent results. While earlier meta-analyses indicated that bedtime dosing significantly reduces myocardial infarction (MI) risk, more recent research has presented conflicting evidence. Therefore, we aimed to evaluate the impact of bedtime versus morning dosing of antihypertensive drugs on cardiovascular outcomes. Methods: We conducted a systematic search across PubMed, EMBASE, and Web of Science databases, covering studies published from inception to 16 July 2025, to identify relevant randomized controlled trials. We calculated risk ratios (RRs) for dichotomous outcomes along with the corresponding 95% confidence intervals (CIs). The study protocol was registered in PROSPERO (ID: CRD420251102968). Results: In total, 8 studies involving 64,235 patients were included in our analysis. Compared with morning dosing, bedtime dosing exhibited no significant differences in all-cause mortality (RR: 0.78; 95% CI: 0.59–1.04; P = 0.09), major adverse cardiovascular events (RR: 0.80; 95% CI: 0.61–1.05; P = 0.10) or cardiovascular death (RR: 0.59; 95% CI: 0.34–1.04; P = 0.07). However, bedtime dosing significantly decreased heart failure risk (RR: 0.67; 95% CI: 0.46–0.96; P = 0.03), lowered clinical systolic blood pressure (mean difference: −3.27 mmHg; 95% CI: −4.13 to −2.41; P < 0.00001), and improved non-dipper conversion (RR: 0.61; 95% CI: 0.47–0.77; P < 0.0001). Non-significant trends favoring bedtime dosing were noted for MI and coronary revascularization. Conclusion: For critical outcomes, including MACE, all-cause mortality and cardiovascular death, no statistically significant benefits associated with bedtime dosing were observed. The overall findings are inconsistent, and the observed advantages for endpoints such as heart failure are closely linked to a single research group, necessitating cautious interpretation. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251102968 , identifier CRD420251102968.

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