Dominick J. Angiolillo MD, PhD, University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, USA, Tel: +1 904 244 3933, Fax: +1 904 244 3102, E-mail:
Thromb Haemost. 2014 Feb;111(2):258-65. doi: 10.1160/TH13-07-0529. Epub 2013 Oct 24.
Increased body weight is independently associated with impaired clopidogrel pharmacodynamic (PD) response. Prasugrel has more potent PD effects compared with clopidogrel, although its PD effects in obese patients are unknown. The aim of this prospective, randomised, study was to compare the PD effects of standard-dose prasugrel [60 mg loading dose (LD)/10 mg daily maintenance dose (MD)] with high-dose clopidogrel (900 mg LD/150 mg daily MD) in non-diabetic obese [body mass index (BMI) ≥30 kg/m²] patients, with coronary artery disease (CAD) on aspirin therapy. PD assessments (baseline, 2 hours post-LD and 6 ± 2 days after MD) were conducted using four platelet function assays, and the platelet reactivity index (PRI) assessed by VASP was used for sample size estimation. A total of 42 patients with a BMI of 36.42 ± 5.6 kg/m² completed the study. There were no differences in baseline PD measures between groups. At 2 hours post-LD, prasugrel was associated with lower PRI compared with clopidogrel (24.3 ± 5.5 vs 58.7 ± 5.7, p≤0.001), with consistent findings for all assays. At one-week, PRI values on prasugrel MD were lower than clopidogrel MD without reaching statistical significance (34.7 ± 5.8 vs 42.9 ± 5.8, p=0.32), with consistent findings for all assays. Accordingly, rates of high on-treatment platelet reactivity were markedly reduced after prasugrel LD, but not after MD. In conclusion, in non-diabetic obese patients with CAD, standard prasugrel dosing achieved more potent PD effects than high-dose clopidogrel in the acute phase of treatment, but this was not sustained during maintenance phase treatment. Whether an intensified prasugrel regimen is required in obese patients warrants investigation.
体重增加与氯吡格雷药效学（PD）反应受损独立相关。与氯吡格雷相比，普拉格雷具有更强的 PD 作用，尽管其在肥胖患者中的 PD 作用尚不清楚。本前瞻性、随机、研究的目的是比较标准剂量普拉格雷[60 毫克负荷剂量（LD）/10 毫克每日维持剂量（MD）]与高剂量氯吡格雷（900 毫克 LD/150 毫克每日 MD）在非糖尿病肥胖[体重指数（BMI）≥30 kg/m²]患者中的 PD 效应，这些患者在阿司匹林治疗的基础上患有冠状动脉疾病（CAD）。PD 评估（基线、LD 后 2 小时和 MD 后 6±2 天）使用四种血小板功能测定法进行，并用 VASP 评估血小板反应指数（PRI）进行样本量估算。共有 42 名 BMI 为 36.42±5.6 kg/m²的患者完成了该研究。两组之间的基线 PD 测量值无差异。在 LD 后 2 小时，普拉格雷与氯吡格雷相比，PRI 较低（24.3±5.5 vs 58.7±5.7，p≤0.001），所有测定法均有一致的发现。在一周时，普拉格雷 MD 的 PRI 值低于氯吡格雷 MD，但无统计学意义（34.7±5.8 vs 42.9±5.8，p=0.32），所有测定法均有一致的发现。因此，普拉格雷 LD 后高治疗血小板反应率显著降低，但 MD 后无明显降低。总之，在患有 CAD 的非糖尿病肥胖患者中，标准普拉格雷剂量在治疗的急性期比高剂量氯吡格雷具有更强的 PD 作用，但在维持期治疗中并未持续。在肥胖患者中是否需要强化普拉格雷治疗方案值得进一步研究。
