Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial
BackgroundDigoxin is widely used in patients with atrial fibrillation despite the lack of randomized controlled trials. Observational studies report conflicting results regarding its association with mortality, perhaps because of residual confounding by the presence of heart failure (HF). Methods an...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-07-01
|
| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.117.006035 |
| _version_ | 1818315131403108352 |
|---|---|
| author | Alon Eisen Christian T. Ruff Eugene Braunwald Rose A. Hamershock Basil S. Lewis Christian Hassager Tze‐Fan Chao Jean Yves Le Heuzey Michele Mercuri Howard Rutman Elliott M. Antman Robert P. Giugliano |
| author_facet | Alon Eisen Christian T. Ruff Eugene Braunwald Rose A. Hamershock Basil S. Lewis Christian Hassager Tze‐Fan Chao Jean Yves Le Heuzey Michele Mercuri Howard Rutman Elliott M. Antman Robert P. Giugliano |
| author_sort | Alon Eisen |
| collection | DOAJ |
| description | BackgroundDigoxin is widely used in patients with atrial fibrillation despite the lack of randomized controlled trials. Observational studies report conflicting results regarding its association with mortality, perhaps because of residual confounding by the presence of heart failure (HF). Methods and ResultsIn the ENGAGE AF‐TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation‐Thrombolysis in Myocardial Infarction 48) trial, clinical outcomes of patients with atrial fibrillation with and without HF were examined by baseline digoxin use during a median follow‐up of 2.8 years. HF was defined at baseline as prior or current clinical stage C or D HF. Of 21 105 patients enrolled, 6327 (30%) were treated with digoxin at baseline. Among patients without HF (n=8981), digoxin use (20%) was independently associated with sudden cardiac death (adjusted hazard ratio, 1.51; 95% CI, 1.10–2.08), with no significant interaction by age, sex, left ventricular ejection fraction, renal function, or concomitant medications (P>0.05 for each). Consistent results were observed using propensity matching (adjusted hazard ratio for sudden cardiac death, 1.90; 95% CI, 1.36–2.65). Among patients with HF (n=12 124), digoxin use (37%) was associated with an increase in all‐cause death, cardiovascular death, sudden cardiac death, and death caused by HF/cardiogenic shock (P<0.01 for each), but not with noncardiovascular death, stroke/systemic embolism, or myocardial infarction. ConclusionsIn this observational analysis of patients with atrial fibrillation without investigator‐reported HF, digoxin use was significantly associated with sudden cardiac death. While residual confounding cannot be excluded, the association between digoxin use and worse clinical outcomes highlights the need to examine digoxin use, particularly when prescribed to control heart rate in patients with atrial fibrillation in a randomized trial. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00781391. |
| first_indexed | 2024-12-13T09:00:39Z |
| format | Article |
| id | doaj.art-87920ea9ee804eefb5eba9e9047f7419 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-13T09:00:39Z |
| publishDate | 2017-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-87920ea9ee804eefb5eba9e9047f74192022-12-21T23:53:11ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802017-07-016710.1161/JAHA.117.006035Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 TrialAlon Eisen0Christian T. Ruff1Eugene Braunwald2Rose A. Hamershock3Basil S. Lewis4Christian Hassager5Tze‐Fan Chao6Jean Yves Le Heuzey7Michele Mercuri8Howard Rutman9Elliott M. Antman10Robert P. Giugliano11TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MATIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MATIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MATIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MALady Davis Carmel Medical Center, Haifa, IsraelRigshospitalet, Copenhagen, DenmarkTaipei Veterans General Hospital, Taipei, TaiwanGeorges Pompidou Hospital, René Descartes University, Paris, FranceDaiichi‐Sankyo, Parsippany, NJDaiichi‐Sankyo, Parsippany, NJTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MATIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MABackgroundDigoxin is widely used in patients with atrial fibrillation despite the lack of randomized controlled trials. Observational studies report conflicting results regarding its association with mortality, perhaps because of residual confounding by the presence of heart failure (HF). Methods and ResultsIn the ENGAGE AF‐TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation‐Thrombolysis in Myocardial Infarction 48) trial, clinical outcomes of patients with atrial fibrillation with and without HF were examined by baseline digoxin use during a median follow‐up of 2.8 years. HF was defined at baseline as prior or current clinical stage C or D HF. Of 21 105 patients enrolled, 6327 (30%) were treated with digoxin at baseline. Among patients without HF (n=8981), digoxin use (20%) was independently associated with sudden cardiac death (adjusted hazard ratio, 1.51; 95% CI, 1.10–2.08), with no significant interaction by age, sex, left ventricular ejection fraction, renal function, or concomitant medications (P>0.05 for each). Consistent results were observed using propensity matching (adjusted hazard ratio for sudden cardiac death, 1.90; 95% CI, 1.36–2.65). Among patients with HF (n=12 124), digoxin use (37%) was associated with an increase in all‐cause death, cardiovascular death, sudden cardiac death, and death caused by HF/cardiogenic shock (P<0.01 for each), but not with noncardiovascular death, stroke/systemic embolism, or myocardial infarction. ConclusionsIn this observational analysis of patients with atrial fibrillation without investigator‐reported HF, digoxin use was significantly associated with sudden cardiac death. While residual confounding cannot be excluded, the association between digoxin use and worse clinical outcomes highlights the need to examine digoxin use, particularly when prescribed to control heart rate in patients with atrial fibrillation in a randomized trial. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00781391.https://www.ahajournals.org/doi/10.1161/JAHA.117.006035atrial fibrillationdigoxinheart failuremortalitysudden cardiac death |
| spellingShingle | Alon Eisen Christian T. Ruff Eugene Braunwald Rose A. Hamershock Basil S. Lewis Christian Hassager Tze‐Fan Chao Jean Yves Le Heuzey Michele Mercuri Howard Rutman Elliott M. Antman Robert P. Giugliano Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease atrial fibrillation digoxin heart failure mortality sudden cardiac death |
| title | Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial |
| title_full | Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial |
| title_fullStr | Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial |
| title_full_unstemmed | Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial |
| title_short | Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial |
| title_sort | digoxin use and subsequent clinical outcomes in patients with atrial fibrillation with or without heart failure in the engage af timi 48 trial |
| topic | atrial fibrillation digoxin heart failure mortality sudden cardiac death |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.117.006035 |
| work_keys_str_mv | AT aloneisen digoxinuseandsubsequentclinicaloutcomesinpatientswithatrialfibrillationwithorwithoutheartfailureintheengageaftimi48trial AT christiantruff digoxinuseandsubsequentclinicaloutcomesinpatientswithatrialfibrillationwithorwithoutheartfailureintheengageaftimi48trial AT eugenebraunwald digoxinuseandsubsequentclinicaloutcomesinpatientswithatrialfibrillationwithorwithoutheartfailureintheengageaftimi48trial AT roseahamershock digoxinuseandsubsequentclinicaloutcomesinpatientswithatrialfibrillationwithorwithoutheartfailureintheengageaftimi48trial AT basilslewis digoxinuseandsubsequentclinicaloutcomesinpatientswithatrialfibrillationwithorwithoutheartfailureintheengageaftimi48trial AT christianhassager digoxinuseandsubsequentclinicaloutcomesinpatientswithatrialfibrillationwithorwithoutheartfailureintheengageaftimi48trial AT tzefanchao digoxinuseandsubsequentclinicaloutcomesinpatientswithatrialfibrillationwithorwithoutheartfailureintheengageaftimi48trial AT jeanyvesleheuzey digoxinuseandsubsequentclinicaloutcomesinpatientswithatrialfibrillationwithorwithoutheartfailureintheengageaftimi48trial AT michelemercuri digoxinuseandsubsequentclinicaloutcomesinpatientswithatrialfibrillationwithorwithoutheartfailureintheengageaftimi48trial AT howardrutman digoxinuseandsubsequentclinicaloutcomesinpatientswithatrialfibrillationwithorwithoutheartfailureintheengageaftimi48trial AT elliottmantman digoxinuseandsubsequentclinicaloutcomesinpatientswithatrialfibrillationwithorwithoutheartfailureintheengageaftimi48trial AT robertpgiugliano digoxinuseandsubsequentclinicaloutcomesinpatientswithatrialfibrillationwithorwithoutheartfailureintheengageaftimi48trial |