Leoncini Mario, Toso Anna, Maioli Mauro, Angiolillo Dominick J, Giusti Betti, Marcucci Rossella, Abbate Rosanna, Bellandi Francesco
Division of Cardiology, Misericordia e Dolce Hospital, Via Cavour, 2 Prato, Italy,
J Thromb Thrombolysis. 2014 May;37(4):427-34. doi: 10.1007/s11239-013-0966-0.
Diabetes mellitus (DM) is associated with impaired platelet response to clopidogrel. In patients with high on-treatment platelet reactivity (HTPR) while on standard-dose clopidogrel, high-dose atorvastatin enhances the pharmacodynamic (PD) effects of double-dose clopidogrel. It is unknown if similar effects are achieved in patients with DM. This study compare the PD effects of high-dose atorvastatin associated with double dose clopidogrel in HTPR patients with and without DM undergoing elective percutaneous coronary intervention (PCI). This is a post hoc analysis of a prospective randomized PD study that compared double-dose (150 mg) clopidogrel associated with high-dose (80 mg) atorvastatin to double-dose clopidogrel alone in statin naïve patients with HTPR undergoing elective PCI. In this analysis, patients were divided in two groups according to DM (n = 27) and non-DM (n = 49) status. Platelet reactivity was evaluated immediately before PCI and at 30 days using the VerifyNow P2Y12 assay. HTPR was defined as P2Y12 reaction units (PRU) ≥235. Administering high-dose atorvastatin in addition to high-dose clipodogrel, the 30 days absolute PRU changes (106 ± 75 vs 100 ± 42, p = 0.7) and optimal response rates (83 vs 84%; p = 0.9) were similar in DM and non-DM patients. The baseline variables significantly associated with 30-day optimal response to high-dose clopidogrel were: atorvastatin treatment (OR = 7.5 [95% CI 1.19-47]; p = 0.032) in DM patients; PRU values (OR = 0.9 [95% CI 0.95-0.99]; p = 0.031) and creatinine clearance (OR = 1.07 [95% CI 1.008-1.13]; p = 0.025) in non-DM patients. High-dose atorvastatin significantly improved the PD effects of double-dose clopidogrel in DM patients with HTPR undergoing elective PCI.
糖尿病（DM）与血小板对氯吡格雷的反应受损有关。在接受标准剂量氯吡格雷治疗时出现高治疗期血小板反应性（HTPR）的患者中，高剂量阿托伐他汀可增强双倍剂量氯吡格雷的药效学（PD）作用。对于糖尿病患者是否能产生类似效果尚不清楚。本研究比较了高剂量阿托伐他汀联合双倍剂量氯吡格雷在接受择期经皮冠状动脉介入治疗（PCI）的有或无糖尿病的HTPR患者中的PD作用。这是一项对前瞻性随机PD研究的事后分析，该研究将高剂量（80 mg）阿托伐他汀联合双倍剂量（150 mg）氯吡格雷与单纯双倍剂量氯吡格雷在接受择期PCI的未服用他汀类药物的HTPR患者中进行比较。在该分析中，患者根据糖尿病状态分为两组（糖尿病组n = 27，非糖尿病组n = 49）。在PCI前及30天时使用VerifyNow P2Y12分析评估血小板反应性。HTPR定义为P2Y12反应单位（PRU）≥235。在高剂量氯吡格雷基础上加用高剂量阿托伐他汀后，糖尿病患者和非糖尿病患者30天的绝对PRU变化（106±75 vs 100±42，p = 0.7）和最佳反应率（83% vs 84%；p = 0.9）相似。与高剂量氯吡格雷30天最佳反应显著相关的基线变量为：糖尿病患者中的阿托伐他汀治疗（OR = 7.5 [95% CI 1.19 - 47]；p = 0.032）；非糖尿病患者中的PRU值（OR = 0.9 [95% CI 0.95 - 0.99]；p = 0.031）和肌酐清除率（OR = 1.07 [95% CI 1.008 - 1.13]；p = 0.025）。高剂量阿托伐他汀显著改善了接受择期PCI的糖尿病HTPR患者中双倍剂量氯吡格雷的PD作用。
