Timing of blood pressure medication administration does not affect outcomes

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.

Evidence suggests that higher-than-normal levels of BP at night are associated with an increased risk of cardiovascular events. However, trials 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."

Professor Ricky Turgeon, study presenter from the University of British Columbia, Vancouver, Canada

A systematic review and meta-analysis was undertaken that included all parallel-group randomized 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 hospitalization 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 randomization 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.