RESUMEN
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).
Asunto(s)
Aspirina , Agregación Plaquetaria , Femenino , Humanos , Aspirina/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Plaquetas , InflamaciónRESUMEN
Aspirin is traditionally taken once daily in the morning and considered to be effective throughout the 24h interval. Cardiovascular events occur most frequently in the early morning, suggesting that these hours are critical in terms of adequate platelet inhibition. This study therefore assed platelet function in the early morning-8.00 AM-in healthy volunteers, during a once-daily (OD) 80 mg morning in comparison with an OD evening regimen and a twice-daily (BID) 40 mg regimen. It was an open-label randomized cross-over study, comprising 12 healthy subjects. Subjects were allocated to three sequential dosage regimens: 80 mg OD at 8.00 AM, 80mg OD at 8.00 PM, and 40 mg BID at 8.00 AM and PM. Platelet function 12 and 24 hours after aspirin intake was measured by means of serum thromboxane B2 (sTxB2) levels, the collagen/epinephrine closure time (Platelet Function Analyzer(PFA)-200®) and the Aspirin Reaction Units (ARU, VerifyNow®). The results demonstrated that early morning sTxB2 concentrations were 5843pg in the morning regimen, 2877pg in the evening OD regimen, and 3343pg in the BID regimen (morning- vs evening regimen p = < 0.01; morning- vs BID regimen p = < 0.01). Early morning PFA-closure time (p = 0.12)) as well as VerifyNow ARU (p = 0.17) mean values were similar for all three regimens. In conclusion, the OD-morning regimen seems to acquire the lowest level of platelet inhibition during the critical early morning window. Switching to an OD-evening or BID intake seems prudent, although further research on clinical cardiovascular outcome in patients with stable cardiovascular disease is needed.