Stroke and Mortality Risk in Patients with Various Patterns of Atrial Fibrillation: Results from the ENGAGE AF-TIMI 48 Trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48)

Mark S. Link, Robert P. Giugliano, Christian T. Ruff, Benjamin M. Scirica, Heikke Huikuri, Ali Oto, Andrea E. Crompton, Sabina A. Murphy, Hans Lanz, Michele F. Mercuri, Elliott M. Antman, Eugene Braunwald

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background - Whether the pattern of atrial fibrillation (AF) modifies the risk/benefit of anticoagulation is controversial. In ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48), the factor Xa inhibitor edoxaban was noninferior to warfarin in preventing stroke or systemic embolic events and significantly reduced bleeding and cardiovascular mortality. However, detailed analyses by AF pattern have not been reported. Methods and Results - The 21 105 patients were categorized as having paroxysmal (<7 days duration), persistent (≥7 days but <1 year), or permanent (≥1 year or failed cardioversion) AF patterns at randomization. Efficacy and safety outcomes were evaluated during the 2.8 years median follow-up and compared by AF pattern. The primary end point of stroke/systemic embolic event was lower in those patients with paroxysmal AF (1.49%/year), compared with persistent (1.83%/year; P-adj =0.015) and permanent AF (1.95%/year; P-adj =0.004). Overall, all-cause mortality also was lower with paroxysmal (3.0%/year) compared with persistent (4.4%/year; P-adj <0.001) and permanent AF (4.4%/year; P-adj <0.001). Annualized major bleeding rates were similar across AF patterns (2.86% versus 2.65% versus 2.73%). There was no effect modification by treatment assignment. Conclusions - In ENGAGE AF-TIMI 48 trial, patients with paroxysmal AF suffered fewer thromboembolic events and deaths compared with those with persistent and permanent AF. The efficacy and safety profile of edoxaban as compared with warfarin was consistent across the 3 patterns of AF.

Original languageEnglish (US)
Article numbere004267
JournalCirculation: Arrhythmia and Electrophysiology
Volume10
Issue number1
DOIs
StatePublished - Jan 1 2017

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Factor Xa
Atrial Fibrillation
Stroke
Myocardial Infarction
Mortality
Warfarin
Hemorrhage
Safety
Electric Countershock
Random Allocation

Keywords

  • Atrial fibrillation
  • Bleeding
  • Mortality
  • Stroke
  • Thromboembolism

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Stroke and Mortality Risk in Patients with Various Patterns of Atrial Fibrillation : Results from the ENGAGE AF-TIMI 48 Trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48). / Link, Mark S.; Giugliano, Robert P.; Ruff, Christian T.; Scirica, Benjamin M.; Huikuri, Heikke; Oto, Ali; Crompton, Andrea E.; Murphy, Sabina A.; Lanz, Hans; Mercuri, Michele F.; Antman, Elliott M.; Braunwald, Eugene.

In: Circulation: Arrhythmia and Electrophysiology, Vol. 10, No. 1, e004267, 01.01.2017.

Research output: Contribution to journalArticle

Link, Mark S. ; Giugliano, Robert P. ; Ruff, Christian T. ; Scirica, Benjamin M. ; Huikuri, Heikke ; Oto, Ali ; Crompton, Andrea E. ; Murphy, Sabina A. ; Lanz, Hans ; Mercuri, Michele F. ; Antman, Elliott M. ; Braunwald, Eugene. / Stroke and Mortality Risk in Patients with Various Patterns of Atrial Fibrillation : Results from the ENGAGE AF-TIMI 48 Trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48). In: Circulation: Arrhythmia and Electrophysiology. 2017 ; Vol. 10, No. 1.
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abstract = "Background - Whether the pattern of atrial fibrillation (AF) modifies the risk/benefit of anticoagulation is controversial. In ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48), the factor Xa inhibitor edoxaban was noninferior to warfarin in preventing stroke or systemic embolic events and significantly reduced bleeding and cardiovascular mortality. However, detailed analyses by AF pattern have not been reported. Methods and Results - The 21 105 patients were categorized as having paroxysmal (<7 days duration), persistent (≥7 days but <1 year), or permanent (≥1 year or failed cardioversion) AF patterns at randomization. Efficacy and safety outcomes were evaluated during the 2.8 years median follow-up and compared by AF pattern. The primary end point of stroke/systemic embolic event was lower in those patients with paroxysmal AF (1.49{\%}/year), compared with persistent (1.83{\%}/year; P-adj =0.015) and permanent AF (1.95{\%}/year; P-adj =0.004). Overall, all-cause mortality also was lower with paroxysmal (3.0{\%}/year) compared with persistent (4.4{\%}/year; P-adj <0.001) and permanent AF (4.4{\%}/year; P-adj <0.001). Annualized major bleeding rates were similar across AF patterns (2.86{\%} versus 2.65{\%} versus 2.73{\%}). There was no effect modification by treatment assignment. Conclusions - In ENGAGE AF-TIMI 48 trial, patients with paroxysmal AF suffered fewer thromboembolic events and deaths compared with those with persistent and permanent AF. The efficacy and safety profile of edoxaban as compared with warfarin was consistent across the 3 patterns of AF.",
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T1 - Stroke and Mortality Risk in Patients with Various Patterns of Atrial Fibrillation

T2 - Results from the ENGAGE AF-TIMI 48 Trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48)

AU - Link, Mark S.

AU - Giugliano, Robert P.

AU - Ruff, Christian T.

AU - Scirica, Benjamin M.

AU - Huikuri, Heikke

AU - Oto, Ali

AU - Crompton, Andrea E.

AU - Murphy, Sabina A.

AU - Lanz, Hans

AU - Mercuri, Michele F.

AU - Antman, Elliott M.

AU - Braunwald, Eugene

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N2 - Background - Whether the pattern of atrial fibrillation (AF) modifies the risk/benefit of anticoagulation is controversial. In ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48), the factor Xa inhibitor edoxaban was noninferior to warfarin in preventing stroke or systemic embolic events and significantly reduced bleeding and cardiovascular mortality. However, detailed analyses by AF pattern have not been reported. Methods and Results - The 21 105 patients were categorized as having paroxysmal (<7 days duration), persistent (≥7 days but <1 year), or permanent (≥1 year or failed cardioversion) AF patterns at randomization. Efficacy and safety outcomes were evaluated during the 2.8 years median follow-up and compared by AF pattern. The primary end point of stroke/systemic embolic event was lower in those patients with paroxysmal AF (1.49%/year), compared with persistent (1.83%/year; P-adj =0.015) and permanent AF (1.95%/year; P-adj =0.004). Overall, all-cause mortality also was lower with paroxysmal (3.0%/year) compared with persistent (4.4%/year; P-adj <0.001) and permanent AF (4.4%/year; P-adj <0.001). Annualized major bleeding rates were similar across AF patterns (2.86% versus 2.65% versus 2.73%). There was no effect modification by treatment assignment. Conclusions - In ENGAGE AF-TIMI 48 trial, patients with paroxysmal AF suffered fewer thromboembolic events and deaths compared with those with persistent and permanent AF. The efficacy and safety profile of edoxaban as compared with warfarin was consistent across the 3 patterns of AF.

AB - Background - Whether the pattern of atrial fibrillation (AF) modifies the risk/benefit of anticoagulation is controversial. In ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48), the factor Xa inhibitor edoxaban was noninferior to warfarin in preventing stroke or systemic embolic events and significantly reduced bleeding and cardiovascular mortality. However, detailed analyses by AF pattern have not been reported. Methods and Results - The 21 105 patients were categorized as having paroxysmal (<7 days duration), persistent (≥7 days but <1 year), or permanent (≥1 year or failed cardioversion) AF patterns at randomization. Efficacy and safety outcomes were evaluated during the 2.8 years median follow-up and compared by AF pattern. The primary end point of stroke/systemic embolic event was lower in those patients with paroxysmal AF (1.49%/year), compared with persistent (1.83%/year; P-adj =0.015) and permanent AF (1.95%/year; P-adj =0.004). Overall, all-cause mortality also was lower with paroxysmal (3.0%/year) compared with persistent (4.4%/year; P-adj <0.001) and permanent AF (4.4%/year; P-adj <0.001). Annualized major bleeding rates were similar across AF patterns (2.86% versus 2.65% versus 2.73%). There was no effect modification by treatment assignment. Conclusions - In ENGAGE AF-TIMI 48 trial, patients with paroxysmal AF suffered fewer thromboembolic events and deaths compared with those with persistent and permanent AF. The efficacy and safety profile of edoxaban as compared with warfarin was consistent across the 3 patterns of AF.

KW - Atrial fibrillation

KW - Bleeding

KW - Mortality

KW - Stroke

KW - Thromboembolism

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