De-escalation strategy with half-dose prasugrel or ticagrelor on pharmacodynamics and outcome in East Asians patients with acute coronary syndrome

Abstract Background East Asians treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) are exposed to more potent platelet inhibitory response. Whether half-dose de-escalation strategy would be benefit for chronic antiplatelet strategy in East Asian patients with acute coronary syndrome (ACS) remain uncertain. Method In half-dose de-escalation strategy, 129 Korean ACS patients were assigned to receive standard-dose potent P2Y12 inhibitors (n=86, prasugrel [n=38], ticagrelor [n=48]), followed by half-dose reduction at 1 month for maintenance, and was compared to clopidogrel (n=43) as control. The primary safety outcome was any clinically significant bleeding according to BARC (Bleeding Academic Research Consortium) criteria at 12 months. The pharmacodynamic response is accessed by VerifyNow P2Y12 reaction unit (PRU) at 1 month and 3 months post PCI. Results Ticagrelor achieved significantly lower PRU (7 [4–32] vs. 11 [5–76] vs. 167 [97–212]) than prasugrel and clopidogrel, resulting OPR rate 0% vs. 21.6% vs. 58.5%, respectively at 1 month post PCI. Similar results were observed at 3 months (PRU 12 [6–43] in ticagrelor vs. 88 [58–148] in prasugrel vs. 169 [107–199] in clopidogrel), with OPR rate 7.1% vs. 51.5% vs. 65.9%, respectively. At 12 months, the incidence of BARC type-1 or -2 bleeding was significantly higher in potent P2Y12 inhibitors (37.5% in ticagrelor, 34.2% in prasugrel) than in clopidogrel (36.0 vs. 14.0%; HR, 2.86; 95% CI, 1.19–6.87; p=0.018). Conclusion In Korean ACS patients, pharmacodynamic response (OPR rate) with half-dose prasugrel appears comparable to that with clopidogrel, whereas ticagrelor still exhibit potent platelet inhibition either standard or half doses. De-escalation strategy with half-dose potent P2Y12 inhibitor was associated with higher incidence of clinically insignificant bleeding compared with clopidogrel. Optimal dose reduction strategies in potent P2Y12 inhibitors to balance safety and effectiveness remain uncertain, and require further studies. Pharmcodynamics to oral P2Y12 inhibitors Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): National Research Foundation of Korea