Di Lullo Luca, Barbera Vincenzo, Bellasi Antonio, Cozzolino Mario, Russo Domenico, Otranto Giovanni, Santoboni Francesca, Ronco Claudio
U.O.C. Nefrologia e Dialisi, Ospedale L. Parodi Delfino, Colleferro, Rome, Italy.
U.O.C. di Nefrologia, Dialisi, Ospedale Sant'Anna-Como, ASST-Lariana, Como, Italy.
G Ital Nefrol. 2017 Mar;34(Suppl 69):188-204.
Atrial fibrillation (AF) represents the most common arrhythmia in patients with chronic kidney disease (CKD). As in the general population, AF is associated with an increased risk of thromboembolism and stroke, according to progressive decline of glomerular filtration rate (GFR). However, CKD patients, especially those on renal replacement therapy (RRT), also exhibit an increased risk of bleeding, especially from the gastrointestinal tract. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF presenting increased risk of stroke. Limited evidence on efficacy, the increased risk of bleeding as well as some concern regarding the use of warfarin in CKD, has often resulted in the underuse of anticoagulation CKD patients. A large body of evidence suggests that non-vitamin K-dependent oral anticoagulant agents (NOACs) significantly reduce the risk of stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with vitamin K antagonist such as warfarin in normal renal function subjects. Hence, they are currently recommended for patients with atrial fibrillation at risk for stroke. However, NOACs metabolism is largely dependent on the kidneys for elimination and little is known in patients with creatinine clearance <25 ml/min who were excluded from all pivotal phase 3 NOACs trials. This review focuses on the current pharmacokinetic, observational, and prospective data on NOACs in patients with advanced chronic kidney disease (creatinine clearance <25 ml/min) and those on dialysis.
心房颤动(AF)是慢性肾脏病(CKD)患者中最常见的心律失常。与普通人群一样,根据肾小球滤过率(GFR)的逐渐下降,AF与血栓栓塞和中风风险增加相关。然而,CKD患者,尤其是接受肾脏替代治疗(RRT)的患者,出血风险也会增加,尤其是胃肠道出血。口服抗凝是预防房颤患者中风风险增加的最有效形式。关于疗效的证据有限、出血风险增加以及对CKD患者使用华法林的一些担忧,常常导致CKD患者抗凝治疗的使用率不足。大量证据表明,非维生素K依赖的口服抗凝剂(NOACs)可显著降低中风、颅内出血和死亡率的风险,与维生素K拮抗剂(如华法林)相比,在肾功能正常的受试者中,大出血发生率更低或相似。因此,目前推荐将其用于有中风风险的房颤患者。然而,NOACs的代谢很大程度上依赖于肾脏进行清除,而对于肌酐清除率<25 ml/min且被排除在所有关键的3期NOACs试验之外的患者,我们了解甚少。本综述重点关注晚期慢性肾脏病(肌酐清除率<25 ml/min)患者和透析患者中NOACs的当前药代动力学、观察性和前瞻性数据。