Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
Circ Cardiovasc Interv. 2010 Feb 1;3(1):17-26. doi: 10.1161/CIRCINTERVENTIONS.109.880179. Epub 2010 Jan 26.
Optimal platelet inhibition is an important therapeutic adjunct in patients acute myocardial infarction (AMI) undergoing coronary stenting. Whether adjunctive cilostazol to dual antiplatelet therapy (triple antiplatelet therapy) can inhibit enhanced platelet reactivity in patients with AMI yet has not been determined. The aim of this study was to assess the degree of platelet inhibition by triple antiplatelet therapy in patients with AMI.
Immediately after emergency room arrival, patients with AMI received clopidogrel (600-mg loading dose, followed by 75 mg daily) and aspirin (300-mg loading dose and 200 mg daily throughout the study period). After patients underwent coronary stenting (n=90), they were randomly assigned to 1 of 3 groups before discharge: standard group, clopidogrel of 75 mg daily (n=30); high maintenance dose (MD) group, clopidogrel of 150 mg daily (n=30); and triple group, adjunctive cilostazol of 100 mg twice daily to clopidogrel of 75 mg daily (n=30). Platelet reactivity was assessed at predischarge and 30-day follow-up by conventional aggregometry and the VerifyNow P2Y12 assay. Predischarge platelet reactivities were similar in the 3 groups. At 30-day follow-up, inhibition of maximal aggregation with 20 microM ADP stimuli was 6.0% in the standard group, 19.1% in the high-MD group, and 42.4% in the triple group (P<0.001), whereas inhibition of late aggregation with 20microM ADP stimuli was 10.8%, 38.1%, and 66.4%, respectively (P<0.001). Similar results were demonstrated when 5 microM ADP was used. Furthermore, percent changes of P2Y12 reaction unit were significantly different among regimens (10.6% in the standard group, 30.7% in the high-MD group, and 43.0% in the triple group; P<0.001). With respect to high-postclopidogrel platelet reactivity (prespecified as 20 microM ADP-induced maximal aggregation >50% of light transmission), fewer patients in the triple group (13.3%) met the criteria as compared with those in the standard (76.7%) and high-MD groups (56.7%) at 30-day follow-up (P<0.001). In the triple group, there were more potent and consistent platelet inhibitions by all parameters as compared with the high-MD group except for percent changes of P2Y12 reaction unit (P=0.071).
Among patients with AMI undergoing coronary stenting, triple antiplatelet therapy results in a greater antiplatelet effect at 30 days as compared with a high-MD clopidogrel or standard dual antiplatelet therapy.
在接受冠状动脉支架置入术的急性心肌梗死（AMI）患者中，最佳的血小板抑制作用是一种重要的治疗辅助手段。辅助西洛他唑联合双联抗血小板治疗（三联抗血小板治疗）是否能抑制 AMI 患者增强的血小板反应性尚未确定。本研究的目的是评估 AMI 患者三联抗血小板治疗的血小板抑制程度。
AMI 患者在急诊室到达后立即接受氯吡格雷（负荷剂量 600mg，随后每天 75mg）和阿司匹林（负荷剂量 300mg，研究期间每天 200mg）。在患者接受冠状动脉支架置入术（n=90）后，他们在出院前随机分为 3 组：标准组，氯吡格雷每天 75mg（n=30）；高维持剂量（MD）组，氯吡格雷每天 150mg（n=30）；三联组，氯吡格雷每天 75mg 加用西洛他唑 100mg，每日 2 次（n=30）。通过常规聚集仪和 VerifyNow P2Y12 测定法在出院前和 30 天随访时评估血小板反应性。3 组患者出院前血小板反应性相似。在 30 天随访时，用 20μM ADP 刺激时最大聚集的抑制率在标准组为 6.0%，高 MD 组为 19.1%，三联组为 42.4%（P<0.001），而用 20μM ADP 刺激时晚期聚集的抑制率分别为 10.8%、38.1%和 66.4%（P<0.001）。当使用 5μM ADP 时，也得到了相似的结果。此外，不同方案的 P2Y12 反应单位的百分比变化差异有统计学意义（标准组为 10.6%，高 MD 组为 30.7%，三联组为 43.0%；P<0.001）。对于高氯吡格雷后血小板反应性（预定为 20μM ADP 诱导的最大聚集>50%光传输），与标准组（76.7%）和高 MD 组（56.7%）相比，三联组（13.3%）在 30 天随访时符合标准的患者更少（P<0.001）。与高 MD 组相比，三联组除了 P2Y12 反应单位的百分比变化（P=0.071）外，所有参数的血小板抑制作用更加强烈和一致。
在接受冠状动脉支架置入术的 AMI 患者中，与高 MD 氯吡格雷或标准双联抗血小板治疗相比，三联抗血小板治疗在 30 天时具有更强的抗血小板作用。
