Evening intake of aspirin is associated with a more stable 24-h platelet inhibition compared to morning intake: a study in chronic aspirin users

Daily generation of novel platelets may compromise aspirin's platelet inhibitory action, especially near the end of the regular 24-h dosing interval. A contributor to this attenuation could be the endogenous circadian rhythm. The primary objective of this study was to assess platelet activity 12 and 24 h after different times of aspirin intake (c.q. 8.00 AM and 8.00 PM). A randomized open-label crossover study was conducted, comprising outpatients with stable cardiovascular disease taking aspirin once daily. We measured platelet aggregation with the platelet function analyzer (PFA)-200(®) and light transmission aggregometry (LTA). The attenuation of aspirin's inhibitory action was most apparent in the 8.00 AM regimen. The platelet function analyzer-closure time was 78 s faster at 24 h than at 12 h after intake in the 8.00 AM regimen (IQR: 166.8-301 vs. 132.8-301; p = 0.006) and 0 s faster at 24 h than at 12 h after intake in the 8.00 PM regimen (IQR: 198.8-837.0 vs. 169.8-301; p = 0.653). The adenosine diphosphate 1.0 µmol/L maximum amplitude was 5.40% higher at 24 h than at 12 h after intake in the 8.00 AM regimen (95% confidence interval (CI): -0.03--10.8; p = 0.040) and was 0.75% higher 24 h than at 12 h after intake in the 8.00 PM regimen (95% CI: -4.83-3.33; p = 0.705). The platelet inhibitory effect of aspirin decreases after 24 h, particularly after intake in the morning. These results suggest that patients might benefit from evening intake or twice daily intake regimens

The efficacy of aspirin to inhibit platelet aggregation in patients hospitalised with a severe infection: a multicentre, open-label, randomised controlled trial

Patients with severe infection have an increased risk of cardiovascular events. A possible underlying mechanism is inflammation-induced platelet aggregation. We investigated whether hyperaggregation occurs during infection, and whether aspirin inhibits this. In this multicentre, open-label, randomised controlled trial, patients hospitalised due to acute infection were randomised to receive 10 days of aspirin treatment (80 mg 1dd or 40 mg 2dd) or no intervention (1:1:1 allocation). Measurements were performed during infection (T1; days 1–3), after intervention (T2; day 14) and without infection (T3; day > 90). The primary endpoint was platelet aggregation measured by the Platelet Function Analyzer® closure time (CT), and the secondary outcomes were serum and plasma thromboxane B2 (sTxB2 and pTxB2). Fifty-four patients (28 females) were included between January 2018 and December 2020. CT was 18% (95%CI 6;32) higher at T3 compared with T1 in the control group (n = 16), whereas sTxB2 and pTxB2 did not differ. Aspirin prolonged CT with 100% (95%CI 77; 127) from T1 to T2 in the intervention group (n = 38), while it increased with only 12% (95%CI 1;25) in controls. sTxB2 decreased with 95% (95%CI − 97; − 92) from T1 to T2, while it increased in the control group. pTxB2 was not affected compared with controls. Platelet aggregation is increased during severe infection, and this can be inhibited by aspirin. Optimisation of the treatment regimen may further diminish the persisting pTxB2 levels that point towards remaining platelet activity. This trial was registered on 13 April 2017 at EudraCT (2016-004303-32)