Evening Blood Pressure Medication Administration and Cardiovascular Events: Systematic Review and Meta-analysis.

BACKGROUND

Controversy persists whether evening administration of antihypertensive medications reduces cardiovascular events. We aimed to synthesize the randomized evidence comparing the risk of cardiovascular events with evening vs morning administration of antihypertensive medications.

METHODS

We systematically searched MEDLINE, Embase, and CENTRAL from inception through May 13, 2025. We included randomized controlled trials of adults with hypertension comparing evening administration of 1 or more antihypertensive medication(s) to morning administration of all antihypertensive medications with ≥ 500 patient-years per group and median follow-up ≥ 12 months. Two reviewers extracted data, assessed risk of bias, and evaluated certainty of evidence. The primary outcome was the composite of major adverse cardiovascular events, as defined in each trial. Secondary outcomes included all-cause and cardiovascular deaths, myocardial infarctions, strokes, heart failure exacerbations, all-cause unplanned hospitalization/emergency department visits, fractures, glaucoma-related events, and worsening cognition. We obtained summary-level data from all trials and also obtained patient-level outcome data for 2 trials (BedMed and BedMed-Frail). The primary meta-analysis pooled trial-level data using a random-effects frequentist approach.

RESULTS

We included 5 randomized controlled trials with 46,606 patients (mean age 63.2 years, 25,515 men [55%]). Median follow-up was 5.2 years. Evening administration of antihypertensive medications, compared with morning administration, did not reduce the risk of major adverse cardiovascular events in all trials (hazard ratio 0.71, 95% confidence interval 0.43-1.16, I2 = 94%), or when restricted to 3 trials at low risk of bias (hazard ratio 0.94, 95% confidence interval 0.86-1.03; I2 = 0%).

CONCLUSIONS

Among adults with hypertension, evening, compared with morning, administration of antihypertensive medications did not reduce the incidence of cardiovascular events.

REGISTRATION: PROSPERO CRD42024521152.