Suttorp Marit M, Hoekstra Tiny, Ocak Gürbey, van Diepen Anouk T N, Ott Ilka, Mittelman Moshe, Rabelink Ton J, Krediet Raymond T, Dekker Friedo W
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Thromb Res. 2014 Nov;134(5):1081-6. doi: 10.1016/j.thromres.2014.07.030. Epub 2014 Aug 1.
BACKGROUND: Erythropoiesis-stimulating agents (ESA) have been associated with a higher cardiovascular event and mortality rate in dialysis patients. The ESA-associated risk of arterial thrombotic events is mainly based on composite endpoints of anemia-correction trials targeting high hemoglobin levels. The ESA-associated risk of venous thromboembolism (VTE) has not been studied in dialysis patients yet. We therefore aimed to determine the association between ESA use and dose with ischemic stroke, myocardial infarction (MI) and VTE. MATERIALS AND METHODS: In NECOSAD, a Dutch cohort study of incident dialysis patients, data on ESA use and dose, comorbidities and laboratory parameters were routinely collected every 6 months. Thrombotic events were collected by chart review of all dialysis patients from 6 participating centers. Time-dependent Cox regression analysis was performed to calculate hazard ratios (HR) with 95% confidence interval (CI) for ischemic stroke, MI and VTE with updated information on ESA use and dose. RESULTS: Patients with ESA had a 2 times lower ischemic stroke rate than patients without ESA: adjusted HR 0.45 (95% CI 0.23-0.90), and an adjusted HR of 1.12 (95% CI 0.58-2.14) for MI. No evident ESA dose response effect was present. Unadjusted HR for VTE was 0.41 (95% CI 0.11-1.50) for patients with ESA compared to patients without, but the low event rate made further adjustments impossible. CONCLUSIONS: In our observational cohort of dialysis patients, reflecting everyday clinical practice, ESA was not associated with an excess of thrombotic events. Further investigation is needed to enlighten the true cause of ESA-associated cardiovascular events and mortality.
背景:促红细胞生成素(ESA)与透析患者较高的心血管事件和死亡率相关。ESA相关的动脉血栓形成事件风险主要基于针对高血红蛋白水平的贫血纠正试验的复合终点。ESA相关的静脉血栓栓塞(VTE)风险在透析患者中尚未得到研究。因此,我们旨在确定ESA的使用和剂量与缺血性卒中、心肌梗死(MI)和VTE之间的关联。 材料与方法:在荷兰一项针对新发病透析患者的队列研究NECOSAD中,每6个月定期收集关于ESA使用和剂量、合并症及实验室参数的数据。通过对6个参与中心的所有透析患者进行病历审查来收集血栓形成事件。采用时间依赖性Cox回归分析,利用ESA使用和剂量的最新信息计算缺血性卒中、MI和VTE的风险比(HR)及95%置信区间(CI)。 结果:使用ESA的患者缺血性卒中发生率比未使用ESA的患者低2倍:校正后HR为0.45(95%CI 0.23 - 0.90),MI的校正后HR为1.12(95%CI 0.58 - 2.14)。未发现明显的ESA剂量反应效应。与未使用ESA的患者相比,使用ESA的患者VTE的未校正HR为0.41(95%CI 0.11 - 1.50),但由于事件发生率低,无法进行进一步校正。 结论:在我们反映日常临床实践的透析患者观察性队列中,ESA与血栓形成事件增多无关。需要进一步研究以阐明ESA相关心血管事件和死亡率的真正原因。
Nephrol Dial Transplant. 2012-2-8