Jin Cai-De, Kim Moo-Hyun, Song Kai, Jin Xuan, Lee Kwang-Min, Park Jong-Sung, Cho Young-Rak, Yun Sung-Cheol, Lee Michael S
Department of Cardiology, Dong-A University Hospital, Busan 49201, Korea.
Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China.
J Clin Med. 2021 Jun 18;10(12):2699. doi: 10.3390/jcm10122699.
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 ( = 39, 60 mg loading dose (LD)/10 mg maintenance dose (MD)), ticagrelor ( = 40, 180 mg LD/90 mg MD), or clopidogrel ( = 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.
接受强效P2Y12抑制剂（普拉格雷或替格瑞洛）治疗的东亚人通常会出现更强的血小板抑制反应，从而导致大出血风险增加。半量递减策略是否能改善韩国急性冠状动脉综合征（ACS）患者的净临床获益仍不确定。共有120例患者被实用地随机分为普拉格雷组（n = 39，负荷剂量（LD）60mg/维持剂量（MD）10mg）、替格瑞洛组（n = 40，LD 180mg/MD 90mg）或氯吡格雷组（n = 41，LD 600mg/MD 75mg），1个月后进行半量减量，或常规剂量75mg氯吡格雷。主要终点是最佳血小板反应性（OPR）的发生率，定义为3个月时通过VerifyNow检测的P2Y12反应单位（PRU）值在85至208之间。与普拉格雷和氯吡格雷相比，替格瑞洛治疗的PRU显著更低（31.0±34.5 vs. 93.2±57.1 vs. 153.1±69.4），导致OPR发生率最低（12.5% vs. 48.7% vs. 63.4%）。在9个月时，强效P2Y12抑制剂组的轻微出血显著高于氯吡格雷组（31.6% vs. 12.2%；HR，2.93；95%CI，1.12 - 7.75）。只有少数患者经历缺血性并发症。在韩国ACS患者中，从标准剂量开始使用半量替格瑞洛和普拉格雷的减量策略显著提高了OPR发生率。与半量普拉格雷以及常规剂量氯吡格雷相比，半量替格瑞洛的OPR发生率更低且血小板抑制作用更强。强效P2Y12抑制剂的最佳剂量降低策略需要进一步研究以平衡安全性和疗效。
