TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, Boston, MA, 02115, USA.
University of Brescia, Brescia, Italy.
Eur J Heart Fail. 2016 Sep;18(9):1153-61. doi: 10.1002/ejhf.595. Epub 2016 Jun 28.
In the ENGAGE AF-TIMI 48 trial, edoxaban, a factor Xa inhibitor, was not found to be inferior to warfarin for the prevention of stroke or systemic embolic events (SEE) in patients with atrial fibrillation (AF) and was associated with significantly less bleeding. The higher-dose edoxaban regimen (HDER; 60 mg dose-reduced to 30 mg once daily) has been approved in various countries in Europe, the USA, and Japan. Among patients treated with vitamin K antagonists (VKAs), symptomatic heart failure (HF) is an independent risk factor for lower time-in-therapeutic range, which reduces the efficacy and safety of VKA therapy. We evaluated the efficacy and safety of edoxaban compared with warfarin across the spectrum of HF severity in the ENGAGE AF-TIMI 48 trial.
Of 14 071 patients randomized to well-controlled warfarin or the HDER, 5926 (42%) had no history of HF, 6344 (45%) were in New York Heart Association (NYHA) class I-II, and 1801 (13%) were in NYHA class III-IV. The efficacy of edoxaban compared with warfarin in preventing stroke/SEE was similar in patients without and with HF regardless of the severity of HF; [HDER vs. warfarin: No-HF: hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.69-1.11; NYHA class I-II: HR 0.88, 95% CI 0.69-1.12; NYHA class III-IV: HR 0.83, 95% CI 0.55-1.25; Pinteraction = 0.97]. Compared with warfarin, HDER was consistently associated with lower risk of major bleeding (No-HF: HR 0.82, 95% CI 0.68-0.99; NYHA class I-II: HR 0.79, 95% CI 0.65-0.96; NYHA class III-IV: HR 0.79, 95% CI 0.54-1.17; Pinteraction = 0.96).
The relative efficacy and safety of HDER compared with well-managed warfarin in AF patients with HF were similar to those without HF.
在 ENGAGE AF-TIMI 48 试验中，因子 Xa 抑制剂依度沙班并未显示优于华法林用于预防房颤（AF）患者的中风或全身性栓塞事件（SEE），且出血风险显著降低。更高剂量的依度沙班方案（HDER；60mg 剂量减少至每日 1 次 30mg）已在欧洲、美国和日本的多个国家获得批准。在接受维生素 K 拮抗剂（VKA）治疗的患者中，有症状的心力衰竭（HF）是治疗范围内时间较低的独立危险因素，从而降低了 VKA 治疗的疗效和安全性。我们评估了依度沙班与华法林在 ENGAGE AF-TIMI 48 试验中各种 HF 严重程度谱中的疗效和安全性。
在随机接受控制良好的华法林或 HDER 的 14071 名患者中，5926 名（42%）无 HF 病史，6344 名（45%）为纽约心脏协会（NYHA）I-II 级，1801 名（13%）为 NYHA III-IV 级。与华法林相比，依度沙班在预防中风/SEE 方面的疗效在无 HF 和有 HF 的患者中相似，无论 HF 的严重程度如何；[HDER 与华法林：无 HF：风险比（HR）0.87，95%置信区间（CI）0.69-1.11；NYHA I-II 级：HR 0.88，95%CI 0.69-1.12；NYHA III-IV 级：HR 0.83，95%CI 0.55-1.25；P 交互=0.97]。与华法林相比，HDER 始终与大出血风险降低相关（无 HF：HR 0.82，95%CI 0.68-0.99；NYHA I-II 级：HR 0.79，95%CI 0.65-0.96；NYHA III-IV 级：HR 0.79，95%CI 0.54-1.17；P 交互=0.96）。
在 HF 合并 AF 的患者中，与管理良好的华法林相比，HDER 的相对疗效和安全性与无 HF 的患者相似。
