Andò Giuseppe, Capranzano Piera
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
Cardiovascular Department, Ferrarotto Hospital, University of Catania, Catania, Italy.
Int J Cardiol. 2017 Mar 15;231:162-169. doi: 10.1016/j.ijcard.2016.11.303. Epub 2016 Dec 2.
Currently there is lack of head-to-head comparisons between different Non-Vitamin K Antagonist Oral Anticoagulants (NOACs), especially in more risky subgroups, as those with chronic kidney disease (CKD).
We assessed the relative efficacy and safety of the four NOACs on the market in a systematic review and network meta-analysis of patients with atrial fibrillation (AF) and moderate CKD enrolled in the phase 3 randomized trials. A Bayesian framework was used to perform the network meta-analysis. Treatment hierarchy was assessed by surface under the cumulative ranking (SUCRA) curves.
Five randomized trials including 13,878 AF patients with moderate CKD were identified. Full/Single dose NOACs were associated with significant reductions in the odds of stroke/systemic embolism (odd ratio [OR] 0.79, 95% credible intervals [CrI] 0.67-0.94) and major bleeding (OR 0.74, 95% CrI 0.65-0.86) compared with Warfarin. Dabigatran 150 had the highest probability of being ranked first with respect to efficacy (SUCRA 0.96), whereas Apixaban had the second highest (SUCRA 0.67); Dabigatran 110, Rivaroxaban and Edoxaban High-Dose showed similar probabilities of being ranked first for efficacy (SUCRA 0.54, 0.53, 0.51, respectively); with respect to safety, only Apixaban and Edoxaban High Dose had a probability >50% of being ranked first (SUCRA 0.84 and 0.61, respectively).
Indirect comparisons generated the hypothesis that Apixaban and Edoxaban High-Dose might be more likely associated with a better net clinical profile in AF patients with moderate CKD. These findings may potentially guide physicians in selecting the most appropriate NOAC for each patient, while waiting for dedicated evidences.
目前,不同的非维生素K拮抗剂口服抗凝药(NOACs)之间缺乏直接比较,尤其是在慢性肾病(CKD)等风险较高的亚组中。
我们通过对纳入3期随机试验的房颤(AF)合并中度CKD患者进行系统评价和网状Meta分析,评估了市面上四种NOACs的相对疗效和安全性。采用贝叶斯框架进行网状Meta分析。通过累积排序曲线下面积(SUCRA)评估治疗层次。
共纳入5项随机试验,涉及13878例AF合并中度CKD患者。与华法林相比,全量/单剂量NOACs与显著降低卒中/全身性栓塞几率(比值比[OR]0.79,95%可信区间[CrI]0.67 - 0.94)和大出血几率(OR 0.74,95% CrI 0.65 - 0.86)相关。达比加群150mg在疗效方面排名第一的概率最高(SUCRA 0.96),而阿哌沙班次之(SUCRA 0.67);达比加群110mg、利伐沙班和高剂量依度沙班在疗效方面排名第一的概率相似(分别为SUCRA 0.54、0.53、0.51);在安全性方面,只有阿哌沙班和高剂量依度沙班排名第一的概率>50%(分别为SUCRA 0.84和0.61)。
间接比较得出的假设是,在中度CKD的AF患者中,阿哌沙班和高剂量依度沙班可能更有可能与更好的净临床特征相关。在等待专门证据的同时,这些发现可能会指导医生为每位患者选择最合适的NOAC。