Vilain Katherine, Li Haiyan, Kwong Wingham J, Antman Elliott M, Ruff Christian T, Braunwald Eugene, Cohen David J, Giugliano Robert P, Magnuson Elizabeth A
Saint Luke's Mid America Heart Institute, Kansas City, MO (K.V., H.L., E.A.M.).
Daiichi Sankyo, Inc, Basking Ridge, NJ (W.J.K.).
Circ Cardiovasc Qual Outcomes. 2020 Nov;13(11):e006511. doi: 10.1161/CIRCOUTCOMES.120.006511. Epub 2020 Nov 5.
Background The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) demonstrated noninferiority of once-daily 60 mg (30 mg dose-reduced) edoxaban compared with warfarin for prevention of stroke/systemic embolism in patients with atrial fibrillation. No previous analysis has explored the impact of treatment with edoxaban versus warfarin on rates of hospitalizations. Methods Detailed healthcare resource utilization data from ENGAGE AF-TIMI 48 for the 14 024 randomized patients who received at least one dose of study drug were used to compare the rates of bleeding- and cardiovascular-related hospitalizations for edoxaban versus warfarin. Hospitalization rates were calculated for each treatment group, and relative rates were estimated using Poisson regression. The influence of patient characteristics on the impact of edoxaban versus warfarin was evaluated through the inclusion of interaction terms. Results The overall rate of cardiovascular- or bleeding-related hospitalization was significantly lower for edoxaban than warfarin (relative rate [RR], 0.91 [95% CI, 0.85-0.97], =0.003). Rates of hospitalizations for cardiovascular reasons (RR, 0.91 [95% CI, 0.85-0.97], =0.004), stroke (RR, 0.80 [95% CI, 0.72-0.88], <0.0001), and for each stroke subtype (ischemic: RR, 0.89 [95% CI, 0.81-0.99], =0.03; hemorrhagic: RR, 0.60 [95% CI, 0.54-0.68], <0.0001) were also lower for edoxaban. Notably, significantly greater reductions with edoxaban versus warfarin were seen for ischemic stroke-related hospitalizations in vitamin K antagonist naive patients and patients with CHADS scores 4 to 6, previous stroke or transient ischemic attack, age ≥75, and no previous coronary artery disease. For nonstroke bleeding-related hospitalizations, greater reductions with edoxaban were seen in vitamin K antagonist naive patients, patients with CHADS scores 4 to 6, and patients with moderate renal dysfunction. Conclusions Edoxaban 60 mg (30 mg dose-reduced) was associated with a significantly lower overall rate of cardiovascular- or bleeding-related hospitalization and significant reductions in the subcategories of cardiovascular-related, stroke-related, bleed-related, and nonstroke cardiovascular-related hospitalizations, when compared with warfarin. These results suggest the potential for cost offsets with edoxaban, with even greater reductions in higher-risk patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00781391.
ENGAGE AF-TIMI 48试验（房颤患者使用新一代Xa因子有效抗凝-心肌梗死溶栓48）表明，对于预防房颤患者的卒中/全身性栓塞，每日一次60毫克（剂量减半为30毫克）的依度沙班与华法林相比具有非劣效性。此前尚无分析探讨依度沙班与华法林治疗对住院率的影响。方法：ENGAGE AF-TIMI 48试验中14024例接受至少一剂研究药物的随机分组患者的详细医疗资源利用数据，用于比较依度沙班与华法林的出血相关和心血管相关住院率。计算每个治疗组的住院率，并使用泊松回归估计相对率。通过纳入交互项评估患者特征对依度沙班与华法林影响的作用。结果：依度沙班组心血管或出血相关住院的总体发生率显著低于华法林组（相对率[RR]，0.91[95%CI，0.85-0.97]，P = 0.003）。心血管原因导致的住院率（RR，0.91[95%CI，0.85-0.97]，P = 0.004）、卒中住院率（RR，0.80[95%CI，0.72-0.88]，P<0.0001）以及每种卒中亚型的住院率（缺血性：RR，0.89[95%CI，0.81-0.99]，P = 0.03；出血性：RR，0.60[95%CI，0.54-0.68]，P<0.0001）依度沙班组也较低。值得注意的是，在未使用过维生素K拮抗剂的患者、CHADS评分4至6分、既往有卒中或短暂性脑缺血发作、年龄≥75岁且无既往冠状动脉疾病的患者中可以看到，依度沙班相比华法林在缺血性卒中相关住院方面的降低幅度显著更大。对于非卒中出血相关住院，在未使用过维生素K拮抗剂的患者、CHADS评分4至6分的患者以及中度肾功能不全的患者中，依度沙班的降低幅度更大。结论：与华法林相比，60毫克（剂量减半为30毫克）依度沙班与显著更低的心血管或出血相关住院总体发生率相关，并且在心血管相关、卒中相关、出血相关和非卒中心血管相关住院亚类中显著降低。这些结果表明依度沙班可能具有成本抵消作用，在高危患者中降低幅度更大。注册信息：网址：https://www.clinicaltrials.gov；唯一标识符：NCT00781391
