Verdoia Monica, Schaffer Alon, Barbieri Lucia, Cassetti Ettore, Piccolo Raffaele, Galasso Gennaro, Marino Paolo, Sinigaglia Fabiola, De Luca Giuseppe
*Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità," Eastern Piedmont University, Novara, Italy; †Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy; and ‡Department of Translational Medicine, Centro di Biotecnologie per la Ricerca Medica Applicata (BRMA), Eastern Piedmont University, Novara, Italy.
J Cardiovasc Pharmacol. 2014 Apr;63(4):339-50. doi: 10.1097/FJC.0000000000000052.
New P2Y12 receptor inhibitors have provided new and more potent antiplatelet strategies, although raising several concerns on possible increase of bleedings. The aim of current meta-analysis was to evaluate the efficacy and safety of new adenosine diphosphate (ADP) receptor antagonists as compared with clopidogrel in elective or ACS patients managed invasively.
Literature archives (Pubmed, EMBASE, Cochrane) and main scientific sessions abstracts were scanned for randomized trials comparing new ADP antagonists with clopidogrel in patients with acute coronary syndromes or stable angina. Primary endpoint was mortality. Secondary endpoints were: (1) nonfatal myocardial infarction (MI), (2) recurrent ischemia symptoms or ischemia-driven revascularization (RI/IDR), (3) stent thrombosis (ST), and (4) safety endpoints, defined as for TIMI major bleeding criteria. A total of 8 randomized clinical trials were finally included, for a total population of 67,851 patients. Mean follow-up was 7.6 months, ranging from 48 hours to 30 months. New ADP antagonists significantly reduced mortality {3.1% vs. 3.6%, odds ratio [OR] [95% confidence interval (CI)], 0.86 [0.79-0.94], P = 0.0008, P(het) = 0.18}, with greater impact of oral drugs. Similar benefits were found for MI [6.1% vs. 7%; OR (95% CI) (random-effect model) = 0.88 (0.79-0.98), P = 0.01, P(het) = 0.02], RI [2.7% vs. 3.1%; OR (95% CI) = 0.85 (0.77-0.93), P = 0.0005, P(het) = 0.09], or ST [1.1% vs. 1.7%; OR (95% CI) = 0.60 (0.51-0.71), P < 0.00001, P(het) = 0.13]. By meta-regression analysis, no relationship was observed between benefits in mortality, new MI, RI, and ST with new ADP antagonists and patients' risk profile [beta (95% CI) = -0.01 [-0.30 to 0.27], P = 0.94; beta (95% CI) = -0.05 [-1.49 to 1.43], P = 0.96); beta (95% CI) = 0.19 (-0.18 to 0.57), P = 0.31, and beta (95% CI) = -0.08 (-0.86 to 0.70), P = 0.84, respectively].
Present meta-analysis shows that the new ADP antagonists prasugrel, ticagrelor, and cangrelor are associated to significant reduction of mortality, reinfarction, RI, and ST respect to clopidogrel alone, without significant increase in bleeding complications.
新型P2Y12受体抑制剂提供了新的且更有效的抗血小板策略，尽管引发了对出血可能增加的若干担忧。当前荟萃分析的目的是评估新型二磷酸腺苷（ADP）受体拮抗剂与氯吡格雷相比，在接受侵入性治疗的择期手术患者或急性冠状动脉综合征（ACS）患者中的疗效和安全性。
检索文献数据库（PubMed、EMBASE、Cochrane）以及主要科学会议的摘要，查找比较新型ADP拮抗剂与氯吡格雷在急性冠状动脉综合征或稳定型心绞痛患者中的随机试验。主要终点是死亡率。次要终点包括：（1）非致命性心肌梗死（MI），（2）复发性缺血症状或缺血驱动的血运重建（RI/IDR），（3）支架血栓形成（ST），以及（4）安全性终点，按照心肌梗死溶栓试验（TIMI）大出血标准定义。最终纳入了8项随机临床试验，总共有67,851例患者。平均随访时间为7.6个月，范围从48小时至30个月。新型ADP拮抗剂显著降低了死亡率{3.1% 对3.6%，比值比[OR][95%置信区间（CI）]，0.86[0.79 - 0.94]，P = 0.0008，P(het)=0.18}，口服药物的影响更大。在MI[6.1%对7%；OR（95% CI）（随机效应模型）= 0.88（0.79 - 0.98），P = 0.01，P(het)=0.02]、RI[2.7%对3.1%；OR（95% CI）= 0.85（0.77 - 0.93），P = 0.0005，P(het)=0.09]或ST[1.1%对1.7%；OR（95% CI）= 0.60（0.51 - 0.71），P < 0.00001，P(het)=0.13]方面也发现了类似的益处。通过荟萃回归分析，未观察到新型ADP拮抗剂在死亡率、新发MI、RI和ST方面的益处与患者风险特征之间存在关联[β（95% CI）= -0.01[-0.30至0.27]，P = 0.94；β（95% CI）= -0.05[-1.49至1.43]，P = 0.96）；β（95% CI）= 0.19（-0.18至0.57），P = 0.31，以及β（95% CI）= -0.08（-0.86至0.70），P = 0.84，分别]。
当前的荟萃分析表明，新型ADP拮抗剂普拉格雷、替格瑞洛和坎格雷洛与单独使用氯吡格雷相比，可显著降低死亡率、再梗死、RI和ST，且出血并发症未显著增加。
