Bonten · Thrombosis and haemostasis 2014 · randomized open-label crossover trial · n=14

Effect of aspirin intake at bedtime versus on awakening on circadian rhythm of platelet reactivity. A randomised cross-over trial.

Cited 67 times in the scientific literature.

Level 2 - randomized trial

Individual randomized crossover trial

PubMed 25208590 · doi:10.1160/TH14-05-0453 · record verified 2026-08-28

What was done

A randomised, open-label crossover trial in 14 healthy subjects evaluated the effect of aspirin timing on circadian platelet reactivity. Participants took 80 mg acetylsalicylic acid either on awakening or at bedtime for two 2-week periods separated by a 4-week washout. At the end of each period, blood was drawn every 3 hours to measure COX-1-dependent (VerifyNow-Aspirin, serum thromboxane B2 [STxB2]) and COX-1-independent (flow cytometry CD62p expression, microaggregation) platelet activity.

What was found

VerifyNow platelet reactivity across the whole day was similar between intake on awakening and at bedtime (mean difference: -9 [95% CI -21 to 4]). However, bedtime aspirin reduced the morning peak in COX-1-dependent activity compared to awakening intake (mean difference VerifyNow: -23 Aspirin Reaction Units [95% CI -50 to 4]; STxB2: -1.7 ng/ml [95% CI -2.7 to -0.8]). COX-1-independent assays showed no effect from timing.

Why it matters

Taking aspirin at bedtime suppresses morning peak COX-1-dependent platelet activity better than morning administration, supporting further study of chronotherapy for cardiovascular protection.

Limits

Sample size was very small (n=14), participants were healthy volunteers rather than cardiovascular patients, the trial was open-label, and clinical cardiovascular events were not measured.

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