多廿烷醇治疗老年急性冠状动脉综合征患者药物洗脱支架置入术后血小板高反应性的疗效与安全性研究:SPIRIT研究预设亚组分析

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目的观察多廿烷醇治疗老年急性冠状动脉综合征(acute coronary syndrome,ACS)患者药物洗脱支架(drug eluting stent,DES)置入术后血小板高反应性(high on-treatment platelet reactivity,HPR)的疗效与安全性。方法选取多廿烷醇改善经皮冠状动脉支架置入术后血小板高反应性研究(SPIRIT)中年龄≥60岁、ACS合并HPR患者169例,其中标准双抗组30例(氯吡格雷75 mg、每日1次,维持12个月),双倍氯吡格雷组75例(氯吡格雷150 mg、每日1次,服用30 d,后以75 mg、每日1次,维持至12个月),多廿烷醇组64例(DES置入术后多廿烷醇40 mg、每日1次至术后6个月,氯吡格雷75 mg、每日1次,维持至12个月)。所有患者均接受阿司匹林治疗。主要观察指标为术后30 d时HPR逆转率(定义为血小板聚集率<65%的比例),次要观察指标为24个月时主要不良心血管事件(major adverse cardiovascular event,MACE,包括心源性死亡、非致死性心肌梗死和靶血管血运重建),安全性观察指标为术后24个月按照出血学术研究联合会(bleeding academic research consortium,BARC)等级划分的出血事件。结果术后30 d时,多廿烷醇组HPR逆转率有优于标准双抗组的趋势,但差异无统计学意义(42.9%比23.3%,P=0.068);与双倍氯吡格雷组比较,差异无统计学意义(42.9%比49.3%,P=0.447);术后6个月时,多廿烷醇组HPR逆转率比术后30 d时进一步改善(57.4%比42.9%,P=0.019),且显著优于标准双抗组(57.4%比34.5%,P=0.042),与双倍氯吡格雷组的差异无统计学意义(57.4%比54.1%,P=0.699)。标准双抗组术后24个月MACE事件发生率有高于双倍氯吡格雷组、多廿烷醇组的趋势,但三组间差异并无统计学意义(13.3%比6.7%比4.7%,P=0.352)。双倍氯吡格雷组术后24个月BARC总出血发生率显著高于标准双抗组和多廿烷醇组(17.3%比3.3%比1.6%,P=0.001)。多廿烷醇组、双倍氯吡格雷组和标准双抗组患者术后24个月无MACE事件的累积生存率分别为95.3%、93.3%和86.7%,差异无统计学意义(P=0.146)。结论对于DES置入术后老年ACS合并HPR患者,在标准双抗基础上联用多廿烷醇可以取得与双倍维持剂量氯吡格雷相近的改善HPR的疗效,同时出血风险明显减少,是更为安全、有效的抗血小板治疗策略。 Objective To observe the effect of policosanol on high on-treatment platelet reactivity (HPR) after drug eluting stent (DES) in elderly patients with acute coronary syndrome (ACS) Efficacy and safety. Methods Policosanol was used to improve the platelet hyperreactivity after percutaneous coronary stent implantation (SPIRIT), age ≥ 60 years, 169 patients with ACS and HPR, of which 30 were standard anti-clopidogrel (clopidogrel 75 mg , Once daily for 12 months), 75 patients in the clopidogrel double-dosed group (clopidogrel 150 mg once daily for 30 days and 75 mg once daily for 12 days Month), policosanol group, 64 cases (postoperative policosanol 40 mg DES, daily from 1 to 6 months after surgery, clopidogrel 75 mg, 1 day, up to 12 months ). All patients received aspirin. The primary outcome measure was the HPR reverse rate (defined as the platelet aggregation rate <65%) at 30 days postoperatively. The secondary outcome measure was the major adverse cardiovascular event at 24 months (MACE, including cardiac output Fatal myocardial infarction and target revascularization). The safety observation was based on the bleeding episodes at the level of bleeding academic research consortium (BARC) at 24 months postoperatively. Results At 30 days after operation, the reversal rate of HPR in policosanol group was higher than that of standard double antibody group, but the difference was not statistically significant (42.9% vs. 23.3%, P = 0.068). Compared with double clopidogrel group (42.9% vs 49.3%, P = 0.447). After 6 months, the HPR reversal rate in policosanol group was further improved than that at 30 days (57.4% vs. 42.9%, P = 0.019), and was significantly better than the standard double-antibody group (57.4% vs 34.5%, P = 0.042). There was no significant difference between the two groups (57.4% vs 54.1%, P = 0.699). The incidence of MACE in standard double-antibody group was higher than that in double-clopidogrel group and policosanol group at 24 months after operation, but there was no significant difference among the three groups (13.3% vs 6.7% vs 4.7% , P = 0.352). The incidence of total BARC was significantly higher at 24 months in the double-clopidogrel group than in the standard double-antibody and policosanol groups (17.3% vs 3.3% vs 1.6%, P = 0.001). The cumulative survival rates of non-MACE events at 24 months after policosanol, double clopidogrel and standard double-antibody were 95.3%, 93.3% and 86.7%, respectively, with no significant difference (P = 0.146 ). Conclusions For patients with elderly ACS complicated with HPR after DES insertion, the combination of policosanol with standard double-antibody can achieve the same effect as HPD with double maintenance dose of clopidogrel, and the risk of bleeding is significantly reduced. For safe and effective anti-platelet therapy strategy.
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