Antihypertensive Medication Timing and Cardiovascular Events and Death: The BedMed Randomized Clinical Trial

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• The optimal timing for administering antihypertensive medications remains uncertain, with inconsistent findings from major clinical trials.
• Concerns exist regarding potential adverse effects of bedtime antihypertensive use, including glaucoma-related visual loss and hypotensive/ischemic events.

Purpose of the Study:

• To investigate the impact of bedtime versus morning administration of antihypertensive medications on major cardiovascular events and mortality.
• To assess the safety profile of bedtime antihypertensive dosing.

Main Methods:

• A multicenter, open-label, pragmatic randomized clinical trial involving 3357 adult patients with hypertension across 5 Canadian provinces.
• Participants were randomized to take all once-daily antihypertensive medications either at bedtime (n=1677) or in the morning (n=1680), with blinded end-point assessment.
• Follow-up occurred for a median of 4.6 years, assessing the primary outcome of time to first occurrence of all-cause death or major adverse cardiovascular events (stroke, acute coronary syndrome, heart failure).

Main Results:

• The composite primary outcome occurred at similar rates in both groups (2.3 per 100 patient-years in the bedtime group vs. 2.4 per 100 patient-years in the morning group; adjusted hazard ratio, 0.96; P=.70).
• No significant differences were observed in individual components of the primary outcome, all-cause hospitalizations/emergency department visits, or safety outcomes, including falls, fractures, new glaucoma diagnoses, or cognitive decline.
• Bedtime administration of antihypertensive medications was found to be safe in this population.

Conclusions:

• Bedtime administration of antihypertensive medications in primary care patients with hypertension is safe but does not reduce cardiovascular risk compared to morning dosing.
• The timing of antihypertensive medication administration does not appear to alter the medication's risks and benefits.
• Treatment timing decisions should prioritize patient preferences to enhance adherence and potentially improve long-term management.