Schriger D L, Herbert M E
UCLA School of Medicine, UCLA Emergency Medicine Center, Los Angeles, CA 90024-2924, USA.
Ann Emerg Med. 2001 Sep;38(3):249-55. doi: 10.1067/mem.2001.117881.
Guidelines from the American Heart Association and the American College of Cardiology, as well as numerous review articles, have strongly and enthusiastically recommended that platelet glycoprotein IIb/IIIa inhibitors be used in patients with medically managed unstable angina or non-ST-segment myocardial infarction (UA/NSTEMI). We explore whether there is sufficient experimental evidence to justify these recommendations. We review the 4 large randomized trials of US Food and Drug Administration-approved platelet glycoprotein IIb/IIIa inhibitors that included medically managed UA/NSTEMI patients, first taking each trial's results at face value and then in the context of likely biases. The risk differences, unadjusted for potential biases, are 2.5% (0.6%, 4.4%) for the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) study, 2.3% (-1.9%, 6.5%) for the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study (tirofiban plus heparin), 0.9% (-0.9%, 2.8%) for the Platelet Glycoprotein IIb/IIIa in Unstable Angina Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, -0.2% (-1.7%, 1.3%) for the least harmful treatment arm of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-IV) trial, and -1.9% (-6.8%, 3.0%) for the PRISM-PLUS study (tirofiban alone) (positive numbers indicate benefit). The 95% confidence interval produced by combining the studies using a random effects model is -1.3% to 3.2% (mean 0.9%); this is consistent with drugs providing a small benefit, no benefit, or causing harm. Confounding caused by the nonrandom selection of patients for percutaneous transluminal coronary angioplasty and coronary artery bypass grafting in all trials except GUSTO-IV and problems arising from the fact that enrolled patients were much sicker than typical UA/NSTEMI patients are likely to have biased the studies away from the null and make an assertion of benefit even more tenuous. Given the equivocal results, it would appear that the authors are relying on opinion rather than evidence to formulate their conclusions. Clinicians should understand that opinion and factors other than medical evidence may influence the content of the recommendations.
美国心脏协会和美国心脏病学会发布的指南，以及众多综述文章，都强烈且积极地推荐在接受药物治疗的不稳定型心绞痛或非ST段抬高型心肌梗死（UA/NSTEMI）患者中使用血小板糖蛋白IIb/IIIa抑制剂。我们探讨是否有足够的实验证据来支持这些推荐。我们回顾了美国食品药品监督管理局批准的4项关于血小板糖蛋白IIb/IIIa抑制剂的大型随机试验，这些试验纳入了接受药物治疗的UA/NSTEMI患者，首先直接看待每项试验的结果，然后考虑可能存在的偏倚。在未对潜在偏倚进行校正的情况下，缺血综合征管理中的血小板受体抑制（PRISM）研究的风险差异为2.5%（0.6%，4.4%），不稳定体征和症状受限患者缺血综合征管理中的血小板受体抑制（PRISM-PLUS）研究（替罗非班加肝素）为2.3%（-1.9%，6.5%），使用依替巴肽治疗不稳定型心绞痛中血小板糖蛋白IIb/IIIa受体抑制（PURSUIT）试验为0.9%（-0.9%，2.8%），全球应用链激酶和组织型纤溶酶原激活剂治疗闭塞冠状动脉（GUSTO-IV）试验危害最小治疗组为-0.2%（-1.7%，1.3%），PRISM-PLUS研究（单独使用替罗非班）为-1.9%（-6.8%，3.0%）（正数表示有益）。使用随机效应模型合并这些研究得出的95%置信区间为-1.3%至3.2%（均值0.9%）；这与药物带来小益处、无益处或造成危害是一致的。除GUSTO-IV外的所有试验中，经皮冠状动脉腔内血管成形术和冠状动脉旁路移植术患者的非随机选择所导致的混杂因素，以及入组患者比典型UA/NSTEMI患者病情严重得多这一事实所引发的问题，可能使研究结果偏离无效假设，从而使关于有益的断言更加站不住脚。鉴于结果不明确，作者似乎是依靠观点而非证据来得出他们的结论。临床医生应该明白，观点以及医学证据之外的因素可能会影响推荐内容。
