University of Pécs, Heart Institute, Division of Interventional Cardiology, Hungary.
Thromb Haemost. 2013 Jan;109(1):93-101. doi: 10.1160/TH12-06-0377. Epub 2012 Nov 29.
Administration of a P2Y 12 -receptor antagonist in addition to aspirin is mandatory in patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary intervention (PCI) to reduce the occurrence of thrombotic events; however, their impact on mortality and stroke is unclear. We aimed to evaluate the influence of moderate (clopidogrel) or potent (prasugrel/ticagrelor) P2Y 12 -receptor inhibition on major cardiovascular outcomes among patients with ACS or undergoing PCI. Systematic literature search was performed to find randomised, controlled clinical trials comparing the clinical impact of clopidogrel with placebo or prasugrel/ticagrelor versus clopidogrel. Outcome measures included cardiovascular death, myocardial infarction (MI), total stroke and intracranial haemorrhage (ICH). Random-effects model with Mantel-Heanszel weighting was used to pool outcomes into a meta-analysis. Four studies comparing clopidogrel with placebo and five trials comparing clopidogrel with new P2Y 12 -receptor inhibitors were identified including a total of 107,473 patients. Compared to placebo, clopidogrel reduced the risk of cardiovascular death (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.87-0.99, p=0.02), MI (OR 0.80; 95%CI 0.74-0.88, p<0.00001) and stroke (OR 0.84; 95%CI 0.72-0.97, p=0.02), without influencing risk for ICH (OR 0.96; 95%CI 0.69-1.33, p=0.79). Treatment with prasugrel/ticagrelor provided additional benefit over clopidogrel regarding cardiovascular mortality (OR 0.86; 95%CI 0.78-0.94, p=0.002) and MI (OR: 0.83; 95%CI 0.74-0.93, p<0.001), but no advantage in stroke (OR: 1.06; 95%CI 0.88-1.26, p=0.55) and in ICH (OR: 1.16; 95%CI 0.75-1.81; p=0.49) was observed. Increased potency of P2Y 12 -receptor inhibition is associated with decreased risk in cardiovascular death and MI; however, this association is not true in case of stroke, where potent P2Y 12 -receptor antagonists have no incremental benefit over clopidogrel.
在急性冠状动脉综合征（ACS）或接受经皮冠状动脉介入治疗（PCI）的患者中，除阿司匹林外，还必须使用 P2Y12 受体拮抗剂，以降低血栓事件的发生；然而，其对死亡率和卒中的影响尚不清楚。我们旨在评估中等强度（氯吡格雷）或强效（普拉格雷/替格瑞洛）P2Y12 受体抑制对 ACS 或接受 PCI 的患者主要心血管结局的影响。进行了系统的文献检索，以寻找比较氯吡格雷与安慰剂或普拉格雷/替格瑞洛与氯吡格雷的临床影响的随机对照临床试验。结局指标包括心血管死亡、心肌梗死（MI）、总卒中以及颅内出血（ICH）。采用 Mantel-Heanszel 加权的随机效应模型将结局汇总到荟萃分析中。确定了四项比较氯吡格雷与安慰剂的研究和五项比较氯吡格雷与新型 P2Y12 受体抑制剂的试验，共纳入了 107473 名患者。与安慰剂相比，氯吡格雷降低了心血管死亡风险（比值比[OR]：0.93；95%置信区间[CI]：0.87-0.99，p=0.02）、MI（OR 0.80；95%CI 0.74-0.88，p<0.00001）和卒中（OR 0.84；95%CI 0.72-0.97，p=0.02），但不影响 ICH 风险（OR 0.96；95%CI 0.69-1.33，p=0.79）。与氯吡格雷相比，普拉格雷/替格瑞洛治疗在心血管死亡率（OR 0.86；95%CI 0.78-0.94，p=0.002）和 MI（OR：0.83；95%CI 0.74-0.93，p<0.001）方面提供了额外的益处，但在卒中（OR：1.06；95%CI 0.88-1.26，p=0.55）和 ICH（OR：1.16；95%CI 0.75-1.81；p=0.49）方面没有获益。P2Y12 受体抑制作用的增强与心血管死亡和 MI 风险降低相关；然而，在卒中方面，这种相关性并不成立，强效 P2Y12 受体拮抗剂与氯吡格雷相比没有额外的获益。
