冠状动脉支架术后三联抗血小板药物治疗对血小板功能的影响

The effects of post coronary stenting triple antiplatelet therapies on platelet functions

目的探讨三联抗血小板药物治疗对冠状动脉(冠脉)支架术后患者血小板活化和聚集功能的影响。方法120例冠心病行冠脉支架植入术患者,随机分为三联组(阿司匹林、氯吡格雷和西洛他唑)和两联组(阿司匹林和氯吡格雷),三联组于术后第1天起加服西洛他唑。两组分别于术后第1天服用西洛他唑前及第5天测定血小板活化复合物(PAC-1)和CD_(62)p,同时测定5μmol/L及20μmol/L ADP诱导的血小板最大聚集率(MPAR)。结果两组临床基线资料及CD_(62)p、PAC-1和MPAR基线值差异均无统计学意义。分别计算各指标第二次测定值与基线值的差值,两组ΔMPAR差异无统计学意义,但三联组和两联组ΔCD_(62)p和ΔPAC-1分别为[(5.12±11.25)%比(1.08±4.97)%,P＜0.05]和[(12.12±12.30)%比(2.22±15.15)%,P＜0.01]。对急性冠脉综合征(ACS)患者亚组分析结果表明三联组ΔMPAR(5μmol/L)[(8.68±10.35)％比(2.92±13.06)%,P=0.018]、ΔMPAR(20μmol/L)[(11.05±11.14)%比(5.16±13.27)%,P=0.019]、ΔCD_(62)p[(5.57±12.08)％比(1.35±4.42)%,P=0.028】和ΔPAC-1[(11.62±12.73)%比(1.29±15.73)%,P= 0.001]均显著高于两联组。3个月临床随访显示三联组与两联组主要不良心、脑血管事件发生率分别为0和3.3%(2/60),出血发生率分别为5%(3/60)和3.3%(2/60),均无统计学意义。结论三联抗血小板药物治疗与常规两联治疗相比能更有效地抑制冠脉支架术后血小板活化和聚集,但其疗效和安全性还需大规模临床试验证实。

Objective To explore the effects of triple antiplatelet therapy on platelet aggregation and activation in patients who underwent coronary stenting. Methods 120 in-hospital coronary heart disease patients with coronary stenting were randomized to two groups receiving either triple antiplatelet drugs of aspirin and clopidogrel combined with cilostazol or dual antiplatelet drugs of aspirin and clopidogrel. On the first clay after stenting cilostazol was added to the triple group patients who were previously administered aspirin and clopidogrel. Expressions of PAC-1 and CD62 p which indicate platelet activation were assessed with flow cytometry and the maximal platelet aggregation rate（MPAR） induced by 5 and 20 μmol/L ADP was measured at the day before receiving cilostazol and the fifth day after stenting, respectively. Results The baseline clinical characteristics did not differ significantly between the two groups. There were no significant differences in the baseline level of MPAR CD62p and PAC-1 at the first day after stenting between the two groups. The margins between the two measurements were [ （6. 44 ± 14.44）% vs （5. 41 ± 13.77）% ,P 〉 0. 05 ] for AMPAR induced by 5 μmol/L ADP, [ （ 8.50 ± 15.50） % vs （7.84 ± 14.21 ） %, P 〉 0. 05 ] for AMPAR induced by 20 p, mol/L ADP, [ （5. 12 ± 11.25 ） % vs （ 1.08 ± 4.97 ） %, P 〈 0. 05 ] for ACD62 p and [ （ 12. 12 ± 12. 30） % vs （2. 22 ± 15. 15 ） %, P 〈 0. 01 ] for APAC-1 in the triple and dual group patients, respectively. Among the above measurements, △CD62 p and △PAC-1 in the triple group patients were significantly higher than those in the dual group patients although AMPAR did not significantly differ between the two groups at the fifth day after stenting. Subgroup analysis for patients with acute coronary syndrome （ACS） showed that AMPAR induced by 5 μmol/L ADP[ （8.68 ± 10. 35）% vs （2. 92 ± 13.06）% ,P =0. 018] ,AMPAR induced by 20 μmol/L[ （ 11.05 ± 11. 14）% vs （5.16 ± 13.27）% ,P =0. 019] ,△CD62p [（5.57±12.08）% vs （1.35 ±4.42）% ,P =0.028]and △PAC-1 [（11.62 ±12.73）% vs （1.29 ±15.73） % ,P =0. 001 ] in triple group were significantly higher than that in dual group. At 3-month clinical follow-up, the rate of major adverse cardiac and cerebral events was 0 in the triple group and 3.3% （2/60） in the dual group, and the rate of hemorrhage was 5% （3/60）in the triple group and 3. 3% （2/60） in the dual group, the differences were not statistically significant. Conclusions Compared with dual antiplatelet regimen with aspirin plus clopidogrel, triple antiplatelet therapy with aspirin and clopidogrel combined with cilostazol is more efficient in inhibiting platelet activation and aggregation after coronary stent implantation. Large scale clinical trials are needed to confirm efficacy and safety of the triple antiplatelet regimen.