伴有和不伴有外周动脉疾病的心房颤动患者的缺血和出血风险，以及全剂量和半剂量依度沙班与华法林相比的疗效和安全性：ENGAGE AF-TIMI 48研究的见解
Ischaemic and bleeding risk in atrial fibrillation with and without peripheral artery disease and efficacy and safety of full- and half-dose edoxaban vs. warfarin: insights from ENGAGE AF-TIMI 48.
作者信息
Bonaca Marc P, Antman Elliott M, Cunningham Jonathan W, Wiviott Stephen D, Murphy Sabina A, Halperin Jonathan L, Weitz Jeffrey I, Grosso Michael A, Lanz Hans J, Braunwald Eugene, Giugliano Robert P, Ruff Christian T
机构信息
TIMI Study Group, Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
出版信息
Eur Heart J Cardiovasc Pharmacother. 2022 Sep 29;8(7):695-706. doi: 10.1093/ehjcvp/pvab089.
AIMS
In patients with atrial fibrillation (AF), peripheral artery disease (PAD) is associated with higher rates of stroke and bleeding. Both higher dose edoxaban (60/30 mg) and lower dose edoxaban (30/15 mg) were non-inferior to warfarin for stroke and systemic embolism (SSE) and significantly reduced major bleeding in AF patients in the global study to assess the safety and effectiveness of edoxaban vs standard practice of dosing with warfarin in patients with atrial fibrillation (ENGAGE AF-TIMI 48) trial. Whether the efficacy and safety of these dosing strategies vs. warfarin are consistent in patients with AF and PAD has not been described.
METHODS AND RESULTS
Of 21 105 patients with AF randomized to warfarin, edoxaban 60/30 mg, or edoxaban 30/15 mg, 841 were identified with PAD. Endpoints included major adverse cardiovascular events (MACEs), SSE, and major bleeding. Patients with PAD had higher risk of MACEs [adjusted hazard ratio (HRadj) 1.33, 95% confidence interval (CI) 1.12-1.57, P = 0.001] and cardiovascular (CV) death (HRadj 1.49, 95% CI 1.21-1.83, P < 0.001) than those without PAD, but not major bleeding. The efficacy of edoxaban 60/30 mg vs. warfarin was consistent regardless of PAD (SSE HR; PAD 1.16, 95% CI 0.42-3.20; no-PAD 0.86, 95% CI 0.74-1.02, P-interaction 0.57) as was major bleeding (PAD 0.96, 95% CI 0.54-1.70; no-PAD 0.80, 95% CI 0.70-0.91, P-interaction 0.54). Edoxaban 30/15 mg was inferior for SSE, with significant heterogeneity when stratified by PAD status (P-interaction 0.039).
CONCLUSION
Patients with AF and PAD are at heightened risk of MACEs and CV death vs. those without PAD. The efficacy and safety of edoxaban 60/30 mg vs. warfarin in AF are consistent regardless of PAD; however, edoxaban 30/15 mg is inferior for stroke prevention in AF patients with PAD. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT00781391.
目的
在心房颤动（AF）患者中，外周动脉疾病（PAD）与更高的中风和出血发生率相关。在评估依度沙班与华法林标准给药方案在心房颤动患者中的安全性和有效性的全球研究（ENGAGE AF-TIMI 48试验）中，高剂量依度沙班（60/30毫克）和低剂量依度沙班（30/15毫克）在预防中风和全身性栓塞（SSE）方面均不劣于华法林，且显著降低了AF患者的大出血发生率。目前尚不清楚这些给药策略与华法林相比，在AF合并PAD患者中的疗效和安全性是否一致。
方法和结果
在21105例随机接受华法林、60/30毫克依度沙班或30/15毫克依度沙班治疗的AF患者中，有841例被确诊为PAD。终点包括主要不良心血管事件（MACE）、SSE和大出血。与无PAD的患者相比，PAD患者发生MACE的风险更高[调整后风险比（HRadj）1.33，95%置信区间（CI）1.12-1.57，P = 0.001]，心血管（CV）死亡风险更高（HRadj 1.49，95%CI 1.21-1.83，P < 0.001），但大出血风险无差异。无论是否有PAD，60/30毫克依度沙班与华法林相比的疗效一致（SSE HR；有PAD为1.16，95%CI 0.42-3.20；无PAD为0.86，95%CI 0.74-1.02，交互作用P值为0.57），大出血情况也是如此（有PAD为0.96，95%CI 0.54-1.70；无PAD为0.80，95%CI 0.70-0.91，交互作用P值为0.54）。30/15毫克依度沙班在预防SSE方面效果较差，按PAD状态分层时存在显著异质性（交互作用P值为0.039）。
结论
与无PAD的患者相比，AF合并PAD的患者发生MACE和CV死亡的风险更高。无论是否有PAD，60/30毫克依度沙班与华法林相比在AF中的疗效和安全性是一致的；然而，30/15毫克依度沙班在预防AF合并PAD患者的中风方面效果较差。临床试验注册：ClinicalTrials.gov标识符：NCT00781391。
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