Open AccessEfficacy and Safety of Edoxaban in Patients With Active Malignancy and Atrial Fibrillation: Analysis of the ENGAGE AF ‐ TIMI 48 Trial
Author(s) -
Fanola Christina L.,
Ruff Christian T.,
Murphy Sabina A.,
Jin James,
Duggal Anil,
Babilonia Noe A.,
Sritara Piyamitr,
Mercuri Michele F.,
Kamphuisen Pieter W.,
Antman Elliott M.,
Braunwald Eugene,
Giugliano Robert P.
Publication year - 2018
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.118.008987
Subject(s) - medicine , edoxaban , atrial fibrillation , malignancy , timi , hazard ratio , warfarin , stroke (engine) , interquartile range , cardiology , myocardial infarction , gastroenterology , confidence interval , thrombolysis , rivaroxaban , mechanical engineering , engineering
Background Anticoagulation in patients with malignancy and atrial fibrillation is challenging because of enhanced risks for thrombosis and bleeding and the frequent need for invasive procedures. Data on direct oral antagonists in such patients are sparse. Methods and Results The ENGAGE AF ‐ TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction Study 48) trial randomized 21 105 patients with atrial fibrillation to edoxaban or warfarin. Patients with malignancy, defined as a postrandomization new diagnosis or recurrence of remote cancer, were followed up over a median of 2.8 years. Adjusted Cox proportional hazard models were used to evaluate the safety and efficacy of edoxaban versus warfarin. Over a median of 495 days (interquartile range, 230–771 days), 1153 patients (5.5%) were diagnosed with new or recurrent malignancy, most commonly involving the gastrointestinal tract (20.6%), prostate (13.6%), and lung (11.1%). Malignancy was associated with increased risk of death (adjusted hazard ratio [HR], 3.12; 95% confidence interval [CI], 2.78–3.50) and major bleeding (adjusted HR, 2.45; 95% CI, 2.07–2.89), but not stroke/systemic embolism (adjusted HR, 1.08; 95% CI, 0.83–1.42). Relative outcomes with higher‐dose edoxaban versus warfarin were consistent regardless of malignancy status for stroke/systemic embolism ( HR , 0.60 [95% CI, 0.31–1.15] for malignancy versus HR , 0.89 [95% CI, 0.76–1.05] for no malignancy; interaction P =0.25) and major bleeding ( HR , 0.98 [95% CI, 0.69–1.40] for malignancy versus HR , 0.79 [95% CI, 0.69–1.05] for no malignancy; interaction P =0.31). There was, however, a significant treatment interaction for the composite ischemic end point (ischemic stroke/systemic embolism/myocardial infarction), with greater efficacy of higher‐dose edoxaban versus warfarin in patients with malignancy ( HR , 0.54; 95% CI, 0.31–0.93) compared with no malignancy ( HR , 1.02; 95% CI, 0.88–1.18; interaction P =0.026). Conclusions In patients with atrial fibrillation who develop malignancy, the efficacy and safety profile of edoxaban relative to warfarin is preserved, and it may represent a more practical alternative.