Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
Am Heart J. 2011 Nov;162(5):884-892.e1. doi: 10.1016/j.ahj.2011.08.020.
Dose adjustment of renally excreted antithrombotic drugs is recommended for patients with reduced renal function. We examined the influence of dose modification on bleeding and efficacy.
Based on initial study drug infusion rate, Early GP IIb/IIIa Inhibition in non-ST-segment elevation acute coronary syndromes (EARLY ACS) patients were categorized into groups: standard dose (2 μg/kg/min; estimated creatinine clearance [eCrCl] ≥50 ml/min), adjusted dose (1 μg/kg/min; eCrCl <50 ml/min, per protocol), excess dose (2 μg/kg/min; eCrCl <50 ml/min). We explored relationships among initial dosing, randomized treatment assignment, and bleeding and ischemic end points (96-h composite of death, myocardial infarction [MI], recurrent ischemia requiring urgent revascularization or thrombotic bailout, and 30-d death or MI).
Of 8,708 patients with eCrCl and dosing data, 19% had eCrCl <50 ml/min. Of these, 13% received adjusted dose eptifibatide and 6% received an excess dose. Across all dosing groups, no significant reductions were found in ischemic end points between early versus delayed provisional eptifibatide (OR 1.14, 95% CI 0.80-1.65; OR 1.13, 95% CI 0.81-1.56, respectively, for 96-h and 30-d composite end points). Bleeding risk was not significantly increased in the early versus delayed provisional treatment group in either the adjusted (OR 1.50, 95% CI 0.95-2.39) or excess dose group (OR 1.67, 95% CI 0.85-3.39). There were no significant interactions between dose group and treatment strategy on bleeding or efficacy.
Similar to observations in practice, despite guidelines recommendations and protocol guidance, 34% of EARLY ACS patients with reduced renal function failed to receive an appropriately adjusted study drug infusion. Use of an appropriately adjusted eptifibatide infusion was not associated with expected reductions in bleeding among patients with renal insufficiency.
对于肾功能降低的患者，建议调整肾排泄的抗血栓药物剂量。我们研究了剂量调整对出血和疗效的影响。
根据初始研究药物输注率，将非 ST 段抬高急性冠状动脉综合征（EARLY ACS）患者分为标准剂量组（2 μg/kg/min；估计的肌酐清除率[eCrCl]≥50 ml/min）、调整剂量组（1 μg/kg/min；eCrCl＜50 ml/min，符合方案）、过量剂量组（2 μg/kg/min；eCrCl＜50 ml/min）。我们探讨了初始剂量、随机治疗分组与出血和缺血终点（96 小时内死亡、心肌梗死[MI]、需要紧急血运重建或血栓解救的复发性缺血，以及 30 天内死亡或 MI 的复合终点）之间的关系。
在 8708 例有 eCrCl 和剂量数据的患者中，19%的患者 eCrCl＜50 ml/min。其中，13%接受了调整剂量的依替巴肽，6%接受了过量剂量。在所有剂量组中，早期与延迟临时依替巴肽之间未发现缺血终点有显著降低（96 小时和 30 天复合终点的 OR 分别为 1.14（95%CI 0.80-1.65）和 1.13（95%CI 0.81-1.56））。在调整剂量组或过量剂量组中，早期与延迟临时治疗组相比，出血风险均无显著增加（OR 分别为 1.50（95%CI 0.95-2.39）和 1.67（95%CI 0.85-3.39））。在出血或疗效方面，剂量组与治疗策略之间没有显著的相互作用。
与实践中的观察结果相似，尽管有指南推荐和方案指导，仍有 34%的 EARLY ACS 肾功能降低患者未能接受适当调整的研究药物输注。在肾功能不全患者中，使用适当调整的依替巴肽输注并没有预期减少出血。
