Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts.
Stanford University Medical School, Stanford, California.
J Am Coll Cardiol. 2017 Jan 17;69(2):176-185. doi: 10.1016/j.jacc.2016.10.055.
Cangrelor, an intravenous, reversible P2Y antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI).
This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs).
This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator's discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization.
Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; P = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; P = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms.
Cangrelor's efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571).
坎格雷洛，一种静脉内、可逆的 P2Y 拮抗剂，已获准用于接受经皮冠状动脉介入治疗（PCI）的患者。
本研究旨在评估坎格雷洛与氯吡格雷在接受和不接受糖蛋白 IIb/IIIa 抑制剂（GPI）的亚组中的疗效和安全性。
本研究对 3 项 CHAMPION（坎格雷洛与标准治疗以实现血小板抑制的最佳管理）试验进行了汇总、患者水平分析，分析了所有接受 PCI 并接受研究药物的随机患者（n=24902）。仅允许使用挽救性/救援性 GPI，除非在 CHAMPION PCI 中，此时可由现场研究人员决定常规或挽救性/救援性 GPI 的使用。主要疗效终点是随机分组后 48 小时内全因死亡率、心肌梗死、缺血驱动的血运重建或支架血栓形成的复合终点。
总体而言，3173 名患者（12.7%）接受了 GPI，最常见的是依替巴肽（69.4%）。尽管 GPI 的适应证存在差异，但在接受和不接受 GPI 的亚组中，坎格雷洛和氯吡格雷组的基线特征在接受和不接受 GPI 的亚组中均得到了很好的平衡。与氯吡格雷相比，接受 GPI 的患者（4.9% vs. 6.5%；比值比[OR]：0.74；95%置信区间[CI]：0.55 至 1.01）或未接受 GPI 的患者（3.6% vs. 4.4%；OR：0.82；95% CI：0.72 至 0.94；P=0.55）中，坎格雷洛的主要复合终点发生率较低。在接受 GPI 的患者（0.4% vs. 0.5%；OR：0.71；95% CI：0.25 至 1.99）或未接受 GPI 的患者（0.2% vs. 0.1%；OR：1.56；95% CI：0.80 至 3.04；P=0.21）中，坎格雷洛并没有增加 GUSTO 定义的严重/危及生命的出血主要安全性终点。GPI 的使用与两个治疗组的出血风险增加相关。
坎格雷洛在降低接受 PCI 的患者的缺血性并发症方面的疗效在 GPI 给药时得到了维持。无论随机分配至坎格雷洛或氯吡格雷，GPI 的使用与更高的出血率显著相关。（证明坎格雷洛尔疗效的临床试验[PCI]：NCT00305162；坎格雷洛尔与标准治疗以实现血小板抑制的最佳管理[PLATFORM]：NCT00385138；比较需要经皮冠状动脉介入治疗的患者中坎格雷洛尔与氯吡格雷标准治疗的临床试验[PCI] [CHAMPION PHOENIX] [CHAMPION]：NCT01156571）。
