London, United Kingdom – 31 August 2024: Evening administration of blood pressure (BP)-lowering medications did not reduce the risk of cardiovascular events or death compared with morning administration, according to late-breaking research presented in a Hot Line session today at ESC Congress 2024.1
“Evidence suggests that higher-than-normal levels of BP at night are associated with an increased risk of cardiovascular events. However, trials2-5 that have assessed the impact of administering BP-lowering medications at night have shown mixed results. In this meta-analysis, we gathered together all of the trial data and concluded that the timing of dosing does not affect outcomes,” explained study presenter, Professor Ricky Turgeon from the University of British Columbia, Vancouver, Canada.
A systematic review and meta-analysis was undertaken that included all parallel-group randomised controlled trials (RCTs) comparing night-time and morning administration of all BP-lowering medications. Studies had to have at least one cardiovascular outcome of interest, with follow-up of ≥500 patient-years per group and median follow-up ≥12 months. Trials were assessed using the Cochrane Risk of Bias 2 tool.
The primary endpoint was major adverse cardiovascular events (MACE, a composite of death from any cause, non-fatal myocardial infarction, non-fatal stroke and heart failure exacerbation). Secondary endpoints included individual components of MACE, all-cause hospitalisation and specific safety events (fractures, glaucoma-related events and worsening cognition).
Five RCTs were included with 46,606 patients – BedMed,2 BedMed-Frail,2 TIME,3 Hygia4 and MAPEC.5 The BedMed, BedMed-Frail and TIME trials were judged to be at overall low risk of bias, while there were some bias concerns with Hygia and MAPEC, particularly regarding the randomisation process.
Across the five trials, the incidence of MACE was not affected by evening vs. morning dosing (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.43–1.16). In a sensitivity analysis by risk of bias, the HR was 0.94 (95% CI 0.86–1.03) for MACE with evening vs. morning dosing in the three trials judged to have low bias and 0.43 (95% CI 0.26–0.72) in the two trials with bias concerns.
There was no difference in all-cause mortality for evening and morning dosing (HR 0.77; 95% CI 0.51–1.16). Similarly, all other secondary endpoints were not affected by evening vs. morning dosing, including for fractures, glaucoma events and cognitive events.
“Results from the meta-analysis provide conclusive evidence that there is no difference between evening and morning dosing. Patients should take their once-daily BP-lowering medications at whatever time best suits their preferences and circumstances,” concluded Professor Turgeon.
ENDS
Notes to editor
Funding: This study was not funded. Ricky Turgeon is supported by a Michael Smith Health Research BC Health Professional-Investigator award.
Disclosures: Ricky Turgeon has no conflict of interest to declare related to this analysis. Dr. Turgeon was not involved in the BedMed or BedMed-Frail trials in any aspect.
References and notes
1‘Meta-analysis of trials of antihypertensive medication bedtime dosing including individual-patient data from BedMed and BedMed-Frail’ will be discussed during Hot Line 2 on Saturday 31 August in room London.
2‘The BedMed and BedMed-Frail randomised controlled trials - Effect of antihypertensive timing on mortality and morbidity’ will be discussed during Hot Line 2 on Saturday 31 August in room London.
3Mackenzie IS, Rogers A, Poulter NR, et al. Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial. Lancet. 2022;400:1417–1425.
4Hermida RC, Crespo JJ, Dominguez-Sardina M, et al. Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia chronotherapy trial. Eur Heart J. 2020;41:4565–4576.
5Hermida RC, Ayala DE, Mojon A, et al. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int. 2010;27:1629–1651.
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