Tcheng James E
Duke University Health System, Duke Clinical Research Institute, Durham, North Carolina 27705, USA.
J Interv Cardiol. 2006 Oct;19(5):456-63. doi: 10.1111/j.1540-8183.2006.00186.x.
Substantial controversy exists regarding the optimal pharmacologic cocktail for percutaneous coronary intervention (PCI). The most common approach typically includes aspirin, clopidogrel, unfractionated heparin (or enoxaparin), and (variably) a glycoprotein (GP) IIb/IIIa inhibitor. Some substitute bivalirudin with "bail-out" GP IIb/IIIa blockade for heparin and planned GP IIb/IIIa integrin blockade, an approach that necessarily includes aspirin and clopidogrel (for their antiplatelet effects). These shifts in adjunctive treatment paradigms should be examined in the context of available data from clinical studies. Several studies have demonstrated the phenomenon of clopidogrel resistance to be fairly prevalent; even in clopidogrel-responsive patients, steady state is achieved only 4-6 hours after a 600-mg loading dose. It would thus be anticipated that clopidogrel-resistant patients would benefit from GP IIb/IIIa blockade, particularly during the period immediately after intervention. Neither REPLACE-2 nor the recent ACUITY trial demonstrated an efficacy advantage for bivalirudin as a substitute for heparin plus GP IIb/IIIa blockade; instead, any advantage appears to be limited to reducing the propensity for bleeding. As bleeding is directly correlated with the degree of anticoagulation and is further augmented by GP IIb/IIIa blockade, an alternative to the bivalirudin strategy is to simply reduce the amount of heparin anticoagulation during PCI. Finally, the benefit-to-risk ratio of aggressive adjunctive antiplatelet/antithrombotic therapy might be further improved via risk stratification, with patients at higher risk for periprocedural events receiving intensive therapy and lower-risk patients being managed with less intensive regimens focused on minimizing the risk of bleeding.
关于经皮冠状动脉介入治疗（PCI）的最佳药物组合存在大量争议。最常见的方法通常包括阿司匹林、氯吡格雷、普通肝素（或依诺肝素）以及（视情况而定）糖蛋白（GP）IIb/IIIa抑制剂。一些人用比伐卢定替代肝素和计划使用的GP IIb/IIIa整合素阻滞剂进行“补救性”GP IIb/IIIa阻断，这种方法必然包括阿司匹林和氯吡格雷（因其抗血小板作用）。辅助治疗模式的这些转变应结合临床研究的现有数据进行审视。多项研究已证明氯吡格雷抵抗现象相当普遍；即使在对氯吡格雷有反应的患者中，600毫克负荷剂量后也仅在4 - 6小时达到稳态。因此可以预期，氯吡格雷抵抗患者将从GP IIb/IIIa阻断中获益，尤其是在介入治疗后的即刻期间。REPLACE - 2试验和近期的ACUITY试验均未证明比伐卢定作为肝素加GP IIb/IIIa阻断的替代物有疗效优势；相反，任何优势似乎仅限于降低出血倾向。由于出血与抗凝程度直接相关，并且会因GP IIb/IIIa阻断而进一步加剧，比伐卢定策略的一种替代方法是在PCI期间简单减少肝素抗凝的用量。最后，通过风险分层可能会进一步改善积极的辅助抗血小板/抗血栓治疗的风险效益比，围手术期事件风险较高的患者接受强化治疗，而低风险患者则采用侧重于将出血风险降至最低的强度较低的治疗方案进行管理。
