Key result
Bedtime antihypertensive dosing fails to reduce MACE compared with morning dosing.
Why the study?
Previous studies on the optimal timing for antihypertensive medication have yielded inconsistent results, with earlier meta-analyses favoring bedtime dosing to reduce MI risk while recent studies presented conflicting evidence.
Does bedtime dosing of antihypertensive medications reduce major adverse cardiovascular events and mortality compared to morning dosing in patients with hypertension?
Meta-Analysis (n=64,235)
Yes
Does bedtime dosing of antihypertensive medications reduce major adverse cardiovascular events and mortality compared to morning dosing in patients with hypertension?
Relative Risk: 0.8 (95% CI 0.61–1.05)
Absolute Event Rate: 6% vs 8.3%
p-value: p=0.10
This updated meta-analysis demonstrates that administering antihypertensive medications at bedtime does not provide a statistically significant reduction in all-cause mortality, MACE, or cardiovascular death compared to morning administration.
Bedtime dosing does not reduce MACE versus morning; challenges prior chronotherapy claims and supports morning administration as standard.
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.
No takes yet. Share an insight, caveat, or question.
Wang et al. (2026) conducted a meta-analysis in Hypertension (n=64,235). Bedtime dosing of antihypertensive medication vs. Morning dosing of antihypertensive medication was evaluated on Major adverse cardiovascular events (MACE) (RR 0.80, 95% CI 0.61-1.05, p=0.10). Bedtime administration of antihypertensive medications did not significantly reduce major adverse cardiovascular events compared with morning dosing (RR 0.80, 95% CI 0.61-1.05, p=0.10).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: