Very-low-dose twice-daily aspirin maintains platelet inhibition and improves haemostasis during dual-antiplatelet therapy for acute coronary syndrome

Abstract

Higher aspirin doses may be inferior in ticagrelor-treated acute coronary syndrome (ACS) patients and reducing bleeding risk whilst maintaining antithrombotic benefits could improve outcomes. We characterized the pharmacodynamics of a novel dual-antiplatelet-therapy regimen consisting of verylow-dose twice-daily (BD) aspirin with standard-dose ticagrelor. A total of 20 ticagrelor-treated ACS patients entered a randomized crossover to take aspirin 20 mg BD (12-hourly) during one 14-day period and 75 mg once-daily (OD) in the other. After 14 days of treatment, serum thromboxane (TX)B 2 and light-transmittance aggregometry were assessed pre-and 2 h post-morning-dose, bleeding time was measured post-dose, and TXA 2 and prostacyclin stable metabolites were measured in urine collected 2 h post-morning-dose. Data are expressed as mean ± SD. After 14 days treatment, serum TXB 2 levels were significantly greater 2 h post-dosing with aspirin 20 mg BD vs. 75 mg OD (3.0 ± 3.6 ng/mL vs. 0.8 ± 1.9 ng/mL; p = 0.018) whereas pre-dosing levels were not significantly different (3.5 ± 4.1 ng/mL vs. 2.5 ± 3.1 ng/mL, p = 0.23). 1-mmol/L arachidonic acid-induced platelet aggregation was similarly inhibited by both regimens pre-dose (8.5 ± 14.3% vs. 5.1 ± 3.6%, p = 0.24) and post-dose (8.7 ± 14.2% vs. 6.6 ± 5.3%; p = 0.41). Post-dose bleeding time was shorter with 20 mg BD (680 ± 306 s vs. 834 ± 386 s, p = 0.02). Urinary prostacyclin and TX metabolite excretion were not significantly different. In conclusion, compared to aspirin 75 mg OD, aspirin 20 mg BD provided consistent inhibition of platelet TXA 2 release and aggregation, and improved post-dose hemostasis, in ticagrelor-treated ACS patients. Further studies are warranted to assess whether this regimen improves the balance of clinical efficacy and safety.

Thrombotic Complications in Patients with COVID-19: Pathophysiological Mechanisms, Diagnosis, and Treatment

“…Upon activation, several key processes occur. First, arachidonic acid is converted to thromboxane A 2 , a potent pro-aggregatory and vasoconstrictive factor [ 12 ]. Second, platelets degranulate.…”

Measurement of Thromboxane Biosynthesis in Health and Disease

“…Similarly, several independent studies have consistently shown the superior biochemical efficacy of a strategy based on shortening the dosing interval versus a strategy of maintaining or increasing the once daily dose of aspirin in patients with type-2 diabetes mellitus (Spectre et al, 2011; Rocca et al, 2012; Bethel et al, 2016), undergoing CABG (Paikin et al, 2015; Cavalca et al, 2017), or presenting with an acute coronary syndrome (Parker et al, 2019).…”

Ticagrelor: clinical development and future potential

“…Therefore, lower-than-standard dose aspirin could hypothetically reduce the risk of bleeding and associated complications of COX-2 inhibition while maintaining anti-thrombotic efficacy. A recent study (WIL-LOW ACS) characterised a novel regimen of very-low-dose aspirin (20 mg BD) plus ticagrelor over two weeks in 20 patients with recent ACS [188]. Compared with standard-dose aspirin (75 mg OD) plus ticagrelor, the novel regimen reduced peak COX-1 inhibition, which was associated with a significant reduction in bleeding time and without a significant difference in arachidonic acid-induced platelet aggregation.…”