Efficacy and safety of edoxaban in patients with active malignancy and atrial fibrillation

Analysis of the engage AF-TIMI 48 trial

Christina Fanola, Christian T. Ruff, Sabina A. Murphy, James Jin, Anil Duggal, Noe A. Babilonia, Piyamitr Sritara, Michele F. Mercuri, Pieter W. Kamphuisen, Elliott M. Antman, Eugene Braunwald, Robert P. Giugliano

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere008987
JournalJournal of the American Heart Association
Volume7
Issue number16
DOIs
StatePublished - Aug 1 2018

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Atrial Fibrillation
Safety
Confidence Intervals
Neoplasms
Warfarin
Embolism
Stroke
Hemorrhage
edoxaban
Myocardial Infarction
Factor Xa
Proportional Hazards Models
Gastrointestinal Tract
Prostate
Thrombosis
Recurrence
Lung

Keywords

  • Anticoagulants
  • Atrial fibrillation
  • Cancer
  • Edoxaban
  • Malignancy
  • Warfarin

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Efficacy and safety of edoxaban in patients with active malignancy and atrial fibrillation : Analysis of the engage AF-TIMI 48 trial. / Fanola, Christina; 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.

In: Journal of the American Heart Association, Vol. 7, No. 16, e008987, 01.08.2018.

Research output: Contribution to journalArticle

Fanola, C, Ruff, CT, Murphy, SA, Jin, J, Duggal, A, Babilonia, NA, Sritara, P, Mercuri, MF, Kamphuisen, PW, Antman, EM, Braunwald, E & Giugliano, RP 2018, 'Efficacy and safety of edoxaban in patients with active malignancy and atrial fibrillation: Analysis of the engage AF-TIMI 48 trial', Journal of the American Heart Association, vol. 7, no. 16, e008987. https://doi.org/10.1161/JAHA.118.008987
Fanola, Christina ; 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. / Efficacy and safety of edoxaban in patients with active malignancy and atrial fibrillation : Analysis of the engage AF-TIMI 48 trial. In: Journal of the American Heart Association. 2018 ; Vol. 7, No. 16.
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abstract = "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.",
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TY - JOUR

T1 - Efficacy and safety of edoxaban in patients with active malignancy and atrial fibrillation

T2 - Analysis of the engage AF-TIMI 48 trial

AU - Fanola, Christina

AU - Ruff, Christian T.

AU - Murphy, Sabina A.

AU - Jin, James

AU - Duggal, Anil

AU - Babilonia, Noe A.

AU - Sritara, Piyamitr

AU - Mercuri, Michele F.

AU - Kamphuisen, Pieter W.

AU - Antman, Elliott M.

AU - Braunwald, Eugene

AU - Giugliano, Robert P.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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.

AB - 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.

KW - Anticoagulants

KW - Atrial fibrillation

KW - Cancer

KW - Edoxaban

KW - Malignancy

KW - Warfarin

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DO - 10.1161/JAHA.118.008987

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