What is the effect of bedtime aspirin on the risk of recurrent cardiovascular events compared with morning aspirin in patients taking aspirin for prevention of cardiovascular disease (CVD)?
Despite improved medical therapy, still 27,000 patients develop recurrent CVD in the Netherlands each year. The risk of CVD is the highest during the morning hours (6-12 AM). Surprisingly, no interventions have been developed to reduce the excess of cardiovascular events during morning hours. Aspirin is the cornerstone of CVD treatment and bedtime intake of aspirin (chronotherapy) has been shown to reduce morning activity of platelets, which play a key role in CVD events. So, aspirin intake at bedtime might be a simple and novel strategy to reduce recurrent CVD events.
Parallel double blinded randomized clinical trial.
Patients using low-dose (80-100mg) aspirin for prevention of CVD on a daily basis from a multidose drug dispensing unit.
(1) morning aspirin + evening placebo
(2) morning placebo + evening aspirin
- Primary outcome: major adverse cardiovascular events.
- Secondary outcomes:
(1) Time of the day of primary outcome
(2) Severe or moderate bleeding events
(4) platelet function during 24-hours
With a recurrence rate of 7% per year and a reduction of 20% of the primary endpoint, we need to include 4,000 patients in total.