Internal and Cardiovascular Medicine - Stroke Unit, University of Perugia, Perugia, Italy.
Department of Political Science, Statistics Division, University of Perugia, Perugia, Italy.
J Thromb Haemost. 2018 May;16(5):833-841. doi: 10.1111/jth.13985. Epub 2018 Mar 26.
Essential In patients on treatment with direct anticoagulants (DOACs) variation of renal function is common. The effect of variations of renal function over time on major bleeding is not well defined. Variation of renal function over time is an independent predictor of major bleeding. Identifying conditions associated with variation of renal function may increase safety of DOACs.
Background Chronic kidney disease is a risk factor for major bleeding in patients with atrial fibrillation (AF) treated with warfarin. Objective To assess the effect of variations in renal function over time on the risk of major bleeding during treatment with direct oral anticoagulants (DOACs) in patients with non-valvular AF. Methods Consecutive AF patients were prospectively followed after they had received the first DOAC prescription. Estimated glomerular filtration rate (eGFR) was periodically assessed, and the incidence of major bleeding was recorded. A joint survival model was used to estimate the association between variation in eGFR and the risk of major bleeding. Results During a mean follow-up of 575 days, 44 major bleeds occurred in 449 patients (6.1% per patient-year). eGFR over time was inversely and independently associated with the risk of major bleeding; every 1 mL min absolute decrease in eGFR was associated with a 2% increase in the risk of major bleeding (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.01-1.04). A similar effect of the variation in eGFR over time was observed on the risk of clinically relevant non-major bleeding (HR 1.02, 95% CI 1.01-1.03). Deterioration of renal function leading to a change in eGFR staging was associated with an increase in the risk of major bleeding (HR 2.43, 95% CI 1.33-4.45). Conclusions Variation in renal function over time is associated with the risk of major bleeding in AF patients treated with DOACs in real life. Identification of intervening clinical conditions associated with variation in renal function is essential to reduce the risk of major bleeding and to make DOAC treatment more safe.
在接受华法林治疗的房颤（AF）患者中，慢性肾脏病是大出血的一个危险因素。目的：评估肾功能随时间的变化对非瓣膜性 AF 患者接受直接口服抗凝剂（DOAC）治疗时大出血风险的影响。方法：连续 AF 患者在接受首次 DOAC 处方后接受前瞻性随访。定期评估估算肾小球滤过率（eGFR），并记录大出血的发生率。使用联合生存模型来估计 eGFR 变化与大出血风险之间的关系。结果：在平均 575 天的随访期间，449 例患者中有 44 例发生大出血（6.1%/患者年）。随时间变化的 eGFR 与大出血风险呈负相关且独立相关；eGFR 绝对下降 1 mL/min 与大出血风险增加 2%相关（风险比 [HR]1.02，95%置信区间 [CI]1.01-1.04）。随时间变化的 eGFR 对临床相关非大出血风险也有类似的影响（HR 1.02，95%CI 1.01-1.03）。肾功能恶化导致 eGFR 分期改变与大出血风险增加相关（HR 2.43，95%CI 1.33-4.45）。结论：在真实世界中，AF 患者接受 DOAC 治疗时，肾功能随时间的变化与大出血风险相关。确定与肾功能变化相关的干预临床情况对于降低大出血风险和提高 DOAC 治疗安全性至关重要。
