三种低分子量肝素在急性冠脉综合征介入治疗中安全性和有效性的比较研究

Comparison of safety and efficacy of enoxaparin,natroparin and dalteparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention

目的比较三种低分子量肝素(依诺肝素、那屈肝素和达肝素)在急性冠脉综合症(ACS)介入治疗中的安全性和有效性。方法本研究采用前瞻性、随机、单盲、单中心设计,76例入选的ACS患者随机分为依诺肝素组(1mg/kg)、那屈肝素组(0.01ml/kg)和达肝素组(120IU/kg),每12h皮下注射一次,至少使用48h后行冠状动脉造影或经皮冠状动脉介入术(PCI),所有手术在末次注射低分子量肝素(LMWH)后8h以内完成,术中不追加LMWH或普通肝素(UFH),监测三组手术前和手术结束时的部分活化凝血酶原激酶时间(APTT)和抗Xa因子活性,同时观察30d终点事件包括死亡、急性心肌梗死、急性左心衰和靶血管再次重建和严重出血事件。结果三组病例手术前和手术结束时平均APTT差异无统计学意义,术前和手术结束时APTT≥45s的病例数在依诺肝素组、那屈肝素组和达肝素组分别为24例(96.0%)、23例(95.8%)和26例(96.3%),差异无统计学意义。三组手术前和手术结束时抗Xa因子差异无统计学意义,但达到抗Xa因子≥0.5IU/L的比例不同,在依诺肝素组、那屈肝素组和达肝素组分别为:术前23例(92.0%)、21例(87.5%)和17例(63.0%)(P=0.018),手术结束时22例(88 0%)、19例(79.2%)和15例(55.6%)(P=0.022)。30d随访三组终点事件的发生率差异无统计学意义,未发生严重出血事件发生。依诺肝素组发生1例因急性左心衰导致死亡,1例术后血小板<10×10^(12)/L,另有1例输血200ml;那屈肝素组发生1例靶血管再次重建;达肝素组1例术中支架后急性血栓形成,导致急性前间壁心肌梗死。结论依诺肝素、那屈肝素和达肝素在ACS患者心导管室应用中均安全有效,术前皮下注射LMWH 4次且手术在末次注射的8h内完成,不需在冠状动脉造影和介入手术中静脉追加LMWH或UFH。

Objective To compare safety and efficacy of enoxaparin, natroparin and dalteparin in patients with acute coronary syndromes （ACS） undergoing percutaneous coronary intervention （PCI）. Methods In this prospective, randomized and single blinded study, 76 patients with ACS who were planning to undergo PCI were divided into three groups： group enoxaparin （lmg/kg）, group natroparin （0.01ml/kg） and group dalteparin （120IU/kg）. After at least 4 doses of low molecular weight heparins （LMWHs） and within 8 h of the last subcutaneous injection, coronary angiography or PCI was performed without additional LMWH or unfractionated heparin intravenous bolus. Activated partial thromboplastin time （APTT） and anti- Xa activity were determined before and after surgery, and endpoint events including death, acute myocardial infarction, target vessel revascularization and severe hemorrhage events were evaluated in a 30-day follow-up. Results There was no significant difference in APTT before and after PCI among the three groups. The percentage of patients whose APTT was above 45 s was 96.0 % （24 cases）, 95.8 % （23 cases） and 96.3 % （26 cases） in group enoxaparin, natroparin and dalteparin respectively, though the differences were insignificant. Also, there was no significant difference in anti- Xa activity before and after PCI among the three groups. But the percentage of patients whose anti-Xa activity was above 0.5IU/L in group enoxaparin, natroparin and dalteparin was 92.0 % （23 cases ）, 87.5 % （21 cases ） and 63.0 % （ 17cases ） （P=0.018） beforePCI, and 88.0% （22cases）, 79.2% （19cases） and 55.6% （15cases） （P=0.022） afterPCI. The mobility of endpoint events was similar and no severe hemorrhage events occurred in the three groups. In group enoxaparin, one patient died of left heart failure, one patient had a platelet count below 10 × 10^12/ L after PCI, and another patient received 200ml transfusion. In group natroparin, one patient underwent revascularization of the target vessel. In group dalteparin, one patient developed intraoperative acute thrombosis after stenting, resulting in acute anteroseptal myocardial infarction. Conclusions PCI within 8 h of the last dose after at least 4 doses of LMWH （enoxaparin, natroparin or dalteparin） subcutaneous injection without additional LMWH or UFH intravenous bolus in ACS patients seems to be safe and effective.