University of Florida College of Medicine-Jacksonville, Jacksonville, Florida 32209, USA.
JACC Cardiovasc Interv. 2011 Aug;4(8):905-12. doi: 10.1016/j.jcin.2011.05.016.
The aim of this study was to evaluate the impact of the phosphodiesterase (PDE) inhibitor pentoxifylline on platelet function profiles in patients receiving dual antiplatelet therapy (DAPT).
Previous studies have shown that, in patients receiving DAPT, the adjunctive use of a PDE inhibitor enhances platelet inhibition, particularly in those presenting with diabetes mellitus (DM). However, the pharmacodynamic (PD) effects of the PDE inhibitor pentoxifylline on platelet function profiles in DM patients receiving DAPT are unknown.
This was a prospective, randomized, double-blind, parallel design study conducted in DM patients with stable coronary artery disease receiving DAPT. Patients were randomly assigned to either pentoxifylline 400 mg or placebo 3 times daily for 14 days. The PD effects were assessed by vasodilator-stimulated phosphoprotein phosphorylation assay, light transmittance aggregometry, VerifyNow P2Y12 assay (Accumetric, Inc., San Diego, California), and multiple electrode aggregometry at baseline and 14 days. The PD effects were also assessed according the presence or absence of high on-treatment platelet reactivity status.
A total of 40 patients were available for analysis. At 14 days, there were no differences in the P2Y(12) reactivity index as assessed by vasodilator-stimulated phosphoprotein phosphorylation between treatment groups (primary endpoint; p = 0.93). Intra-group comparisons also failed to show any differences between baseline and 14-day P2Y(12) reactivity index assessment in the placebo and pentoxifylline arms (p = 0.61). There were no significant inter- and intra-group differences in all other PD measures. The PD effects did not vary according the presence or absence of high on-treatment platelet reactivity.
Adjunctive treatment with pentoxifylline is not associated with increased platelet inhibitory effects in DM patients with coronary artery disease receiving DAPT.
本研究旨在评估磷酸二酯酶（PDE）抑制剂己酮可可碱对接受双联抗血小板治疗（DAPT）的患者血小板功能谱的影响。
先前的研究表明，在接受 DAPT 的患者中，辅助使用 PDE 抑制剂可增强血小板抑制作用，特别是在患有糖尿病（DM）的患者中。然而，在接受 DAPT 的 DM 患者中，PDE 抑制剂己酮可可碱对血小板功能谱的药效学（PD）影响尚不清楚。
这是一项在接受 DAPT 的稳定型冠状动脉疾病合并 DM 的患者中进行的前瞻性、随机、双盲、平行设计研究。患者被随机分配至己酮可可碱 400mg 组或安慰剂组，每日 3 次，疗程为 14 天。PD 效应通过血管扩张刺激磷酸蛋白磷酸化测定、光透射聚集测定、VerifyNow P2Y12 测定（Accumetric，Inc.，加利福尼亚州圣地亚哥）和多电极聚集测定在基线和 14 天时进行评估。PD 效应还根据是否存在高治疗时血小板反应性状态进行评估。
共有 40 例患者可用于分析。在第 14 天，两组间通过血管扩张刺激磷酸蛋白磷酸化测定评估的 P2Y（12）反应指数无差异（主要终点；p = 0.93）。安慰剂和己酮可可碱组的组内比较也未显示在 14 天的 P2Y（12）反应指数评估中与基线相比存在任何差异（p = 0.61）。其他 PD 测量指标在两组间也无显著差异。PD 效应不因高治疗时血小板反应性的存在与否而不同。
在接受 DAPT 的合并冠状动脉疾病的 DM 患者中，辅助使用己酮可可碱与增加血小板抑制作用无关。
