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 very-low-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)B2 and light-transmittance aggregometry were assessed pre- and 2 h post-morning-dose, bleeding time was measured post-dose, and TXA2 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 TXB2 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 TXA2 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.
Highlights
The combination of the irreversible cyclo-oxygenase (COX) inhibitor aspirin 75–100 mg once-daily (OD) and the P2Y12 inhibitor ticagrelor 90 mg twice-daily (BD) represents a standard recommended regimen of dual antiplatelet therapy (DAPT) in acute coronary syndromes (ACS) [1,2,3,4]
Mean (± standard deviation (SD)) serum thromboxane B2 (TXB2) levels 2 h post-dose were significantly greater when receiving 20 mg BD when compared to 75 mg OD (3.03 ± 3.64 ng/mL vs. 0.83 ± 1.93 ng/mL, p = 0.018) (Table III, Figure 2(a)) and there was no significant difference between the regimens at pre-dose, which corresponds to the trough effect (3.51 ± 4.07 ng/mL vs. 2.48 ± 3.14 ng/mL, p = 0.23) (Table III, Figure 2(a))
DAPT with aspirin and ticagrelor represents a standard maintenance antithrombotic therapy that is recommended as first-line treatment following ACS [3,4,49]
Summary
The combination of the irreversible cyclo-oxygenase (COX) inhibitor aspirin (acetylsalicylic acid) 75–100 mg once-daily (OD) and the P2Y12 inhibitor ticagrelor 90 mg twice-daily (BD) represents a standard recommended regimen of dual antiplatelet therapy (DAPT) in acute coronary syndromes (ACS) [1,2,3,4]. The PLATelet inhibition and patient Outcomes (PLATO) study showed that DAPT with aspirin and ticagrelor was superior to the previous standard regimen of aspirin and clopidogrel in ACS, reducing the incidence of major adverse cardiovascular events (MACE). Despite such potent antiplatelet therapy, the residual MACE risk remains around 10% at 1 year [5]. Continuing DAPT with aspirin and reduced-dose ticagrelor longterm in stable high-risk individuals further decreases the risk of MACE compared with aspirin alone [6]. Concern about bleeding risk may, dissuade clinicians from recommending DAPT, in the long-term, to the potential detriment of high-risk patients
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