Pharmacodynamics and Outcomes of a De-Escalation Strategy with Half-Dose Prasugrel or Ticagrelor in East Asians Patients with Acute Coronary Syndrome: Results from HOPE-TAILOR Trial.

Cai-De Jin,Michael S Lee,Young-Rak Cho,Sung-Cheol Yun,Xuan Jin,Jong-Sung Park,Moo-Hyun Kim,Kai Song,Kwang-Min Lee

doi:10.3390/jcm10122699

Abstract

East Asians treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) generally experience more intense platelet inhibitory responses resulting in an increased risk of major bleeding. Whether a half-dose de-escalation strategy improves the net clinical benefit in Korean patients with acute coronary syndrome (ACS) remains uncertain. A total of 120 patients were pragmatically randomized to either prasugrel (n = 39, 60 mg loading dose (LD)/10 mg maintenance dose (MD)), ticagrelor (n = 40, 180 mg LD/90 mg MD), or clopidogrel (n = 41, 600 mg LD/75 mg MD) followed by a half-dose reduction at 1 month, or conventional dose 75 mg clopidogrel. The primary endpoint was the incidence of optimal platelet reactivity (OPR), defined as a P2Y12 reaction unit (PRU) value between 85 and 208 (by VerifyNow) at 3 months. Ticagrelor treatment achieved a significantly lower PRU compared with prasugrel and clopidogrel (31.0 ± 34.5 vs. 93.2 ± 57.1 vs. 153.1 ± 69.4), resulting in the lowest rate of OPR (12.5% vs. 48.7% vs. 63.4%). At 9 months, the minor bleeding was significantly higher with potent P2Y12 inhibitors than with clopidogrel (31.6% vs. 12.2%; HR, 2.93; 95% CI, 1.12–7.75). Only a few patients experienced ischemic complications. In Korean ACS patients, a de-escalation strategy with half-dose ticagrelor and prasugrel from standard dose increased the OPR rate significantly. Half-dose ticagrelor had a lower OPR rate and greater platelet inhibition compared with half-dose prasugrel as well as conventional-dose clopidogrel. Optimal dose reduction strategies for potent P2Y12 inhibitors require further investigation to balance safety and efficacy.

Highlights

The TRITONTIMI 38 and PLATO trials both reported that a potent oral P2Y12 inhibitor was superior to clopidogrel in reducing ischemic events but came at the cost of increased major bleedings [1,2]
For low-dose loading and maintenance doses of prasugrel for high platelet reactivity (HPR) and CYP2C19 polymorphic patients, we previously reported that half-dose prasugrel achieved a lower rate of HPR and a higher therapeutic window range (30 days) in Korean percutaneous coronary intervention (PCI) patients [9,10]
The study was originally designed as a prospective, randomized, open-label, blinded, endpoint (PROBE) single-center trial in acute coronary syndrome (ACS) patients with three different drug loading strategies and de-escalation to half dose with potent

Summary

Introduction

The TRITONTIMI 38 and PLATO trials both reported that a potent oral P2Y12 inhibitor (prasugrel and ticagrelor, respectively) was superior to clopidogrel in reducing ischemic events but came at the cost of increased major bleedings [1,2]. Current American College of Cardiology/American Heart Association and European Society of Cardiology guidelines recommend prasugrel or ticagrelor as the preferred oral P2Y12 inhibitor for the management of ACS patients undergoing percutaneous coronary intervention (PCI) [3]. East Asian patients have a different pharmacodynamic and pharmacokinetic response to potent P2Y12 inhibitors compared with non-East Asians. The optimal dose for potent P2Y12 inhibitors in East Asians with ACS appears to be different with non-East Asians in daily practice

Methods

Results

Conclusion