Use and outcomes of antiarrhythmic therapy in patients with atrial fibrillation receiving oral anticoagulation: results from the ROCKET AF trial.
BACKGROUND
Antiarrhythmic drugs (AADs) and anticoagulation are mainstays of atrial fibrillation (AF) treatment.


OBJECTIVE
To study the use and outcomes of AAD therapy in anticoagulated patients with AF.


METHODS
Patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial (N = 14,264) were stratified by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across AAD groups as well as across treatment assignment (rivaroxaban or warfarin).


RESULTS
Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone and 537 [3.8%] with other AADs). Amiodarone-treated patients were less often female (38% vs 48%), had more persistent AF (64% vs 40%), and more concomitant heart failure (71% vs 41%) than were patients receiving other AADs. Patients receiving no AAD more closely resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone than in those receiving no AAD (50% vs 58%; P < .0001). Compared with no AAD, neither amiodarone (adjusted hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.74-1.31; P = .9) nor other AADs (adjusted HR 0.66; 95% CI 0.37-1.17; P = .15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Treatment effects of rivaroxaban vs warfarin in patients receiving no AAD were consistent with results from the overall trial (primary end point: adjusted HR 0.82; 95% CI 0.68-0.98; Pinteraction = .06; safety end point: adjusted HR 1.12; 95% CI 0.90-1.24; Pinteraction = .33).


CONCLUSIONS
Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The effect of amiodarone on outcomes in patients receiving rivaroxaban requires further investigation.
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina. Electronic address: benjamin.steinberg@dm.duke.edu.
Benjamin A
BA
Steinberg
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
Anne S
AS
Hellkamp
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
Yuliya
Y
Lokhnygina
Cardiovascular Institute, Mount Sinai Medical Center, New York, New York.
Jonathan L
JL
Halperin
Department of Cardiovascular Medicine, Hospital of the University of Münster, Münster, Germany.
Günter
G
Breithardt
Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Rod
R
Passman
School of Medicine and Pharmacology, The University of Western Australia, Crawley, Australia.
Graeme J
GJ
Hankey
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
Manesh R
MR
Patel
University of Cincinnati College of Medicine, Cincinnati, Ohio.
Richard C
RC
Becker
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Daniel E
DE
Singer
Ruprecht-Karls-University, Heidelberg, Germany.
Werner
W
Hacke
Bayer HealthCare Pharmaceuticals, Montville, New Jersey.
Scott D
SD
Berkowitz
Janssen Research & Development LLC, Raritan, New Jersey.
Christopher C
CC
Nessel
Department of Medicine, Stanford University, Stanford, California.
Kenneth W
KW
Mahaffey
University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
Keith A A
KA
Fox
Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina.
Robert M
RM
Califf
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
Jonathan P
JP
Piccini
D000368:Aged; D000638:Amiodarone / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D000069552:Rivaroxaban; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban; D000638:Amiodarone
Antiarrhythmic drugs; Atrial fibrillation; Outcomes; Rivaroxaban; Warfarin