氯吡格雷反应阴性不稳定型心绞痛患者PCI术后不同抗血小板治疗的早期和晚期疗效观察

Short-term and late-term clinical effects of different anti-platelet treatment on unstable angina patients with negative response of clopidogrel after percutaneous coronary intervention

目的观察氯吡格雷反应阴性的不稳定型心绞痛患者经皮冠脉介入治疗(PCI)术后不同抗血小板治疗方法的早期和晚期临床效果。方法连续入选择期行PCI治疗术后24 h经血栓弹力图测定氯吡格雷反应阴性(ADP%抑制率低于50%)的不稳定型心绞痛患者286例,在双联抗血小板基础上,随机分为2组,双倍剂量组143例给予氯吡格雷双倍剂量(150 mg/d),联合组143例给予氯吡格雷(75 mg/d)联合西洛他唑(200 mg 2次/d)。出院治疗1个月后复测血栓弹力图,了解ADP%抑制率及随访主要心血管事件。随访1 a,观察主要心血管事件及复查冠状动脉造影观察支架内再狭窄发生率。结果双倍剂量组与联合组PCI术后24 h ADP%抑制率分别为(28.7±12.4)%和(29.1±11.6)%,术后1个月时为(43.7±13.6)%和(48.1±14.2)%,2组术后1个月较术后24 h均有明显提高(P均<0.05);联合组术后1个月抑制率较双倍剂量组有增加趋势,但无统计学差异(P>0.05)。术后1个月内2组均无死亡、急性血栓形成及危及生命的大出血,双倍剂量组发生亚急性血栓1例。随访1 a,2组无死亡和大出血事件,双倍剂量组和联合组急性心肌梗死分别为3例和1例,2组比较有显著性差异(P<0.05)。双倍剂量组和联合组发生支架内再狭窄比率分别为9.1%和4.9%,2组比较有显著性差异(P<0.05)。结论氯吡格雷加倍剂量的双联抗血小板治疗和氯吡格雷联合西洛他唑三联抗血小板治疗对血小板聚集的抑制作用明显增强,早期血栓发生率明显下降,出血未见明显增加。三联抗血小板治疗在晚期降低血栓和支架内再狭窄发生率方面可能优于氯吡格雷加倍的双联抗血小板治疗。

Objective It is to observe the short-term and late-term clinical effects of different anti-platelet treatment on un- stable angina patients with negative response of clopidogrel after percutaneous coronary intervention （PCI）. Methods Two hundreds and eighty-six patients with unstable angina verified by clinical features and negative response of clopidogrel tested by thrombelastogram （Platelet inhibition rate induced by adenosine diphosphate （ADP） was lower than 50% ）were investigated consecutively. All patients based on combination therapy of aspirin and clopidogrel were divided randomly into double dose clo- pidogrel （ 150 mg） group（ DC group, n = 143 ） and cilostazol （200 mg/bid） with clopidogreI （ 75 mg） group （ CC group, n = 143 ）. Platelet inhibition rate induced by ADP was retested by thrombelastogram and major cardiovascular events were followed up after 1 month out of hospital. In-stent restenosis rate was observed by reviewing coronary arteriography and major cardiovas- cular events after 1 year out of hospital. Results Platelet inhibition rate induced by ADP was respectively （28.7 ± 12.4） % and （29.1 ±11.6）% before PCI and （43.7 ±13.6）% and （48.1 ±14.2）% after 1 month out of hospital and was higher after 1 month out of hospital than one before PCI （ P 〈 0.05 ） in two groups, though Platelet inhibition rate induced by ADP was higher in CC group than one in DD group after 1 month, no significant change was found in two groups（ P 〉 0.05 ）. There were no death, acute thrombosis and life-threatening massive hemorrhage in two groups, but there was a case of suhacute thrombosis in DD group after 1 month out of hospital. Though death and life-threatening massive hemorrhage were not founded in two groups, there were respectively 3 cases and 1 case of acute cardiac infarction in DD and CC groups after following up I year and the difference was significant（P 〈 0.05） in two groups, ln-stent restenosis rate was respectively 9. 1% in DD group and 4.9%in CC group, the difference was significant between two groups（ P 〈 0.05 ）. Conclusion Inhibition effects of anti-plate- let on three drugs combination of aspirin and clopidogrel and cilostazol and two drugs combination of aspirin and double dose clopidogrel increase obviously. Incidence rate of thrombosis decreases distinctly and life-threatening massive hemorrhage does not increase in short-term, no significant difference was found in two treatment. Three drugs combination may be superior to two drugs combination in reducing incidence rate of late-term thrombosis and in-stent restenosis.