Bavry Anthony A, Elgendy Islam Y, Mahmoud Ahmed, Jadhav Manoj P, Huo Tianyao
North Florida/South Georgia Veterans Health System, Gainesville, Florida, United States of America; Department of Medicine, University of Florida, Gainesville, Florida, United States of America.
Department of Medicine, University of Florida, Gainesville, Florida, United States of America.
PLoS One. 2015 May 26;10(5):e0127832. doi: 10.1371/journal.pone.0127832. eCollection 2015.
Percutaneous coronary intervention with bivalirudin plus bail-out glycoprotein IIb/IIIa inhibitors has been shown to be as effective as unfractionated heparin plus routine glycoprotein IIb/IIIa inhibitors in preventing cardiac ischemic events, but with a lower bleeding risk. It is unknown whether bivalirudin would have the same beneficial effects if compared with heparin when the use of glycoprotein IIb/IIIa inhibitors was similar between treatment arms. We searched the MEDLINE, Web of Science, and Cochrane databases from inception until March 2015 for randomized trials that compared bivalirudin to heparin in patients undergoing percutaneous coronary intervention. We required that the intended use of glycoprotein IIb/IIIa inhibitors was similar between the study groups. Summary estimates were principally constructed by the Peto method. Fifteen trials met our inclusion criteria, which yielded 25,824 patients. Bivalirudin versus heparin was associated with an increased hazard of stent thrombosis (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.15-1.92, P = .002, I2 = 16.9%), with a similar hazard of myocardial infarction (OR 1.09, 95% CI 0.98-1.22, P = .11, I2 = 35.8%), all-cause mortality (OR 0.88, 95% CI 0.72-1.08, P = .21, I2 = 31.5%) and major adverse cardiac events (OR 1.04, 95% CI 0.94-1.14, P = .46, I2 = 53.9%). Bivalirudin was associated with a reduced hazard of major bleeding (OR 0.80, 95% CI 0.70-0.92, P = .001, I2 = 63.5%). The dose of heparin in the control arm modified this association; when the dose of unfractionated heparin in the control arm was ≥ 100 units/kg, bivalirudin was associated with a reduction in major bleeding (OR 0.55, 95% CI 0.45-0.68, P < .0001), but when the dose of unfractionated heparin was ≤ 75 units/kg, bivalirudin was not associated with reduction in bleeding (OR 1.09, 95% CI 0.91-1.31, P = .36). Among patients undergoing PCI, bivalirudin was associated with an increased hazard of stent thrombosis. Bivalirudin may be associated with a reduced hazard of major bleeding; however, this benefit was no longer apparent when compared with a dose of unfractionated heparin ≤ 75 units/kg.
在预防心脏缺血事件方面，使用比伐卢定加补救性糖蛋白IIb/IIIa抑制剂进行经皮冠状动脉介入治疗已被证明与使用普通肝素加常规糖蛋白IIb/IIIa抑制剂一样有效，但出血风险更低。当治疗组之间糖蛋白IIb/IIIa抑制剂的使用情况相似时，与肝素相比，比伐卢定是否会有相同的有益效果尚不清楚。我们检索了MEDLINE、科学网和Cochrane数据库，从建库至2015年3月，查找在接受经皮冠状动脉介入治疗的患者中对比比伐卢定与肝素的随机试验。我们要求研究组之间糖蛋白IIb/IIIa抑制剂的预期使用情况相似。汇总估计主要通过Peto方法构建。15项试验符合我们的纳入标准，共纳入25824例患者。与肝素相比，比伐卢定与支架血栓形成风险增加相关（比值比[OR]1.49，95%置信区间[CI]1.15 - 1.92，P = 0.002，I² = 16.9%），心肌梗死风险相似（OR 1.09，95% CI 0.98 - 1.22，P = 0.11，I² = 35.8%），全因死亡率相似（OR 0.88，95% CI 0.72 - 1.08，P = 0.21，I² = 31.5%），主要不良心脏事件相似（OR 1.04，95% CI 0.94 - 1.14，P = 0.46，I² = 53.9%）。比伐卢定与大出血风险降低相关（OR 0.80，95% CI 0.70 - 0.92，P = 0.001，I² = 63.5%）。对照组中肝素的剂量改变了这种关联；当对照组中普通肝素的剂量≥100单位/千克时，比伐卢定与大出血减少相关（OR 0.55，95% CI 0.45 - 0.68，P < 0.0001），但当普通肝素的剂量≤75单位/千克时，比伐卢定与出血减少无关（OR 1.09，95% CI 0.91 - 1.31，P = 0.36）。在接受经皮冠状动脉介入治疗的患者中，比伐卢定与支架血栓形成风险增加相关。比伐卢定可能与大出血风险降低相关；然而，与剂量≤75单位/千克的普通肝素相比，这种益处不再明显。
