Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)

ROCKET AF Steering Committee and Investigators; Jeffrey B Washam; Susanna R Stevens; Yuliya Lokhnygina; Jonathan L Halperin; Günter Breithardt; Daniel E Singer; Kenneth W Mahaffey; Graeme J Hankey; Scott D Berkowitz; Christopher C Nessel; Keith A A Fox; Robert M Califf; Jonathan P Piccini; Manesh R Patel

doi:10.1016/S0140-6736(14)61836-5

Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)

ROCKET AF Steering Committee and Investigators, Jeffrey B Washam, Susanna R Stevens, Yuliya Lokhnygina, Jonathan L Halperin, Günter Breithardt, Daniel E Singer, Kenneth W Mahaffey, Graeme J Hankey, Scott D Berkowitz, Christopher C Nessel, Keith A A Fox, Robert M Califf, Jonathan P Piccini, Manesh R Patel

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

BACKGROUND: Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in 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 (ROCKET AF).

METHODS: For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767.

FINDINGS: In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076).

INTERPRETATION: Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed.

FUNDING: Janssen Research & Development and Bayer HealthCare AG.

Original language	English
Pages (from-to)	2363-70
Number of pages	8
Journal	The Lancet
Volume	385
Issue number	9985
DOIs	https://doi.org/10.1016/S0140-6736(14)61836-5
Publication status	Published - 13 Jun 2015

Keywords / Materials (for Non-textual outputs)

Aged
Anti-Arrhythmia Agents
Anticoagulants
Atrial Fibrillation
Death, Sudden
Diabetes Mellitus
Digoxin
Factor Xa Inhibitors
Female
Heart Failure
Heart Rate
Humans
Intracranial Embolism
Male
Morpholines
Proportional Hazards Models
Randomized Controlled Trials as Topic
Retrospective Studies
Sex Distribution
Stroke
Thiophenes
Vitamin K
Warfarin

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ROCKET AF Steering Committee and Investigators, Washam, J. B., Stevens, S. R., Lokhnygina, Y., Halperin, J. L., Breithardt, G., Singer, D. E., Mahaffey, K. W., Hankey, G. J., Berkowitz, S. D., Nessel, C. C., Fox, K. A. A., Califf, R. M., Piccini, J. P., & Patel, M. R. (2015). Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). The Lancet, 385(9985), 2363-70. https://doi.org/10.1016/S0140-6736(14)61836-5

ROCKET AF Steering Committee and Investigators ; Washam, Jeffrey B ; Stevens, Susanna R et al. / Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes : a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). In: The Lancet. 2015 ; Vol. 385, No. 9985. pp. 2363-70.

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title = "Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)",

abstract = "BACKGROUND: Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in 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 (ROCKET AF).METHODS: For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767.FINDINGS: In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076).INTERPRETATION: Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed.FUNDING: Janssen Research & Development and Bayer HealthCare AG.",

keywords = "Aged, Anti-Arrhythmia Agents, Anticoagulants, Atrial Fibrillation, Death, Sudden, Diabetes Mellitus, Digoxin, Factor Xa Inhibitors, Female, Heart Failure, Heart Rate, Humans, Intracranial Embolism, Male, Morpholines, Proportional Hazards Models, Randomized Controlled Trials as Topic, Retrospective Studies, Sex Distribution, Stroke, Thiophenes, Vitamin K, Warfarin",

author = "{ROCKET AF Steering Committee and Investigators} and Washam, {Jeffrey B} and Stevens, {Susanna R} and Yuliya Lokhnygina and Halperin, {Jonathan L} and G{\"u}nter Breithardt and Singer, {Daniel E} and Mahaffey, {Kenneth W} and Hankey, {Graeme J} and Berkowitz, {Scott D} and Nessel, {Christopher C} and Fox, {Keith A A} and Califf, {Robert M} and Piccini, {Jonathan P} and Patel, {Manesh R}",

year = "2015",

month = jun,

day = "13",

doi = "10.1016/S0140-6736(14)61836-5",

language = "English",

volume = "385",

pages = "2363--70",

journal = "The Lancet",

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ROCKET AF Steering Committee and Investigators, Washam, JB, Stevens, SR, Lokhnygina, Y, Halperin, JL, Breithardt, G, Singer, DE, Mahaffey, KW, Hankey, GJ, Berkowitz, SD, Nessel, CC, Fox, KAA, Califf, RM, Piccini, JP & Patel, MR 2015, 'Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)', The Lancet, vol. 385, no. 9985, pp. 2363-70. https://doi.org/10.1016/S0140-6736(14)61836-5

Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). / ROCKET AF Steering Committee and Investigators; Washam, Jeffrey B; Stevens, Susanna R et al.
In: The Lancet, Vol. 385, No. 9985, 13.06.2015, p. 2363-70.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes

T2 - a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)

AU - ROCKET AF Steering Committee and Investigators

AU - Washam, Jeffrey B

AU - Stevens, Susanna R

AU - Lokhnygina, Yuliya

AU - Halperin, Jonathan L

AU - Breithardt, Günter

AU - Singer, Daniel E

AU - Mahaffey, Kenneth W

AU - Hankey, Graeme J

AU - Berkowitz, Scott D

AU - Nessel, Christopher C

AU - Fox, Keith A A

AU - Califf, Robert M

AU - Piccini, Jonathan P

AU - Patel, Manesh R

PY - 2015/6/13

Y1 - 2015/6/13

N2 - BACKGROUND: Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in 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 (ROCKET AF).METHODS: For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767.FINDINGS: In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076).INTERPRETATION: Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed.FUNDING: Janssen Research & Development and Bayer HealthCare AG.

AB - BACKGROUND: Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in 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 (ROCKET AF).METHODS: For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767.FINDINGS: In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076).INTERPRETATION: Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed.FUNDING: Janssen Research & Development and Bayer HealthCare AG.

KW - Aged

KW - Anti-Arrhythmia Agents

KW - Anticoagulants

KW - Atrial Fibrillation

KW - Death, Sudden

KW - Diabetes Mellitus

KW - Digoxin

KW - Factor Xa Inhibitors

KW - Female

KW - Heart Failure

KW - Heart Rate

KW - Humans

KW - Intracranial Embolism

KW - Male

KW - Morpholines

KW - Proportional Hazards Models

KW - Randomized Controlled Trials as Topic

KW - Retrospective Studies

KW - Sex Distribution

KW - Stroke

KW - Thiophenes

KW - Vitamin K

KW - Warfarin

U2 - 10.1016/S0140-6736(14)61836-5

DO - 10.1016/S0140-6736(14)61836-5

M3 - Article

C2 - 25749644

SN - 0140-6736

VL - 385

SP - 2363

EP - 2370

JO - The Lancet

JF - The Lancet

IS - 9985

ER -

ROCKET AF Steering Committee and Investigators, Washam JB, Stevens SR, Lokhnygina Y, Halperin JL, Breithardt G et al. Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). The Lancet. 2015 Jun 13;385(9985):2363-70. doi: 10.1016/S0140-6736(14)61836-5