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

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.

Keywords: East Asians; acute coronary syndrome; half-dose reduction; outcomes; pharmacodynamics; prasugrel; ticagrelor.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Patient flow and overall clinical trial design.
Figure 2
Figure 2
Matched-pairs analysis of 1 month versus 3-month pharmacodynamics in each P2Y12 inhibitor group. (a) Prasugrel; (b) ticagrelor; (c) clopidogrel.
Figure 3
Figure 3
Cumulative incidence of safety endpoints (composite of BARC type 1 or 2 bleedings). (a) Kaplan–Meier estimate of safety endpoints at 9 months; (b) Landmark analysis at 1 month for safety endpoints.

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