Institute of Cardiology and Center of Excellence on Aging, "G. d'Annunzio" University, Chieti, Italy.
Division of Cardiovascular Medicine, Brigham and Women's Hospital, TIMI Study Group, Boston, Massachusetts.
J Am Coll Cardiol. 2017 Mar 21;69(11):1363-1371. doi: 10.1016/j.jacc.2016.12.038.
Valvular heart disease (VHD) and atrial fibrillation (AF) often coexist. Phase III trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin excluded patients with moderate/severe mitral stenosis or mechanical heart valves, but variably included patients with other VHD and valve surgeries.
This study aimed to determine relative safety and efficacy of NOACs in patients with VHD.
We performed a meta-analysis of the 4 phase III AF trials of the currently available NOACs versus warfarin in patients with coexisting VHD to assess pooled estimates of relative risk (RR) and 95% confidence intervals (CIs) for stroke/systemic embolic events (SSEE), major bleeding, intracranial hemorrhage (ICH), and all-cause death.
Compared with warfarin, the rate of SSEE in patients treated with higher-dose NOACs was lower and consistent among 13,585 patients with (RR: 0.70; 95% CI: 0.58 to 0.86) or 58,098 without VHD (RR: 0.84; 95% CI: 0.75 to 0.95; interaction p = 0.13). Major bleeding in patients on higher-dose NOACs versus warfarin was similar and consistent among patients with (RR: 0.93; 95% CI: 0.68 to 1.27) or without VHD (RR: 0.85; 95% CI: 0.70 to 1.02; interaction p = 0.63 for VHD/no-VHD difference). Intracranial hemorrhage was lower with higher-dose NOACs than with warfarin irrespective of VHD (RR: 0.47; 95% CI: 0.24 to 0.93, and 0.49; 95% CI: 0.41 to 059, respectively; interaction p = 0.91). No protective effect of higher-dose NOACs in preventing all-cause death seemed to be present in patients with VHD versus without VHD (RR:1.01; 95% CI: 0.90 to 1.14 vs. RR: 0.88; 95% CI: 0.82 to 0.94, respectively; interaction p = 0.03).
High-dose NOACs provide overall efficacy and safety similar in AF patients with or without VHD.
瓣膜性心脏病（VHD）和心房颤动（AF）常同时存在。比较新型口服抗凝剂（NOACs）与华法林的 III 期临床试验排除了中度/重度二尖瓣狭窄或机械心脏瓣膜的患者，但不同程度地纳入了其他 VHD 和瓣膜手术的患者。
本研究旨在确定 VHD 患者使用 NOAC 的相对安全性和疗效。
我们对目前可用的 4 种 NOAC 与华法林在 VHD 合并 AF 患者中的 III 期 AF 试验进行荟萃分析，以评估 SSEE、大出血、颅内出血（ICH）和全因死亡的相对风险（RR）和 95%置信区间（CI）的汇总估计值。
与华法林相比，高剂量 NOAC 治疗的患者 SSEE 发生率较低，且在 13585 例有（RR：0.70；95%CI：0.58 至 0.86）或 58098 例无 VHD（RR：0.84；95%CI：0.75 至 0.95；交互 p=0.13）的患者中一致。与华法林相比，高剂量 NOAC 治疗的患者大出血发生率相似且一致，在有（RR：0.93；95%CI：0.68 至 1.27）或无 VHD（RR：0.85；95%CI：0.70 至 1.02；交互 p=0.63）的患者中一致。高剂量 NOAC 治疗的患者颅内出血发生率低于华法林，无论是否存在 VHD（RR：0.47；95%CI：0.24 至 0.93 和 0.49；95%CI：0.41 至 0.59，分别；交互 p=0.91）。高剂量 NOAC 似乎没有预防 VHD 患者全因死亡的保护作用，与无 VHD 的患者相比（RR：1.01；95%CI：0.90 至 1.14 与 RR：0.88；95%CI：0.82 至 0.94，分别；交互 p=0.03）。
高剂量 NOAC 在 VHD 合并或不合并 AF 的患者中提供了相似的疗效和安全性。
