Dronedarone in high-risk permanent atrial fibrillation

Stuart J Connolly; A John Camm; Jonathan L Halperin; Campbell Joyner; Marco Alings; John Amerena; Dan Atar; Álvaro Avezum; Per Blomström; Martin Borggrefe; Andrzej Budaj; Shih-Ann Chen; Chi Keong Ching; Patrick Commerford; Antonio Dans; Jean-Marc Davy; Etienne Delacrétaz; Giuseppe Di Pasquale; Rafael Diaz; Paul Dorian; Greg Flaker; Sergey Golitsyn; Antonio Gonzalez-Hermosillo; Christopher B Granger; Hein Heidbüchel; Josef Kautzner; June Soo Kim; Fernando Lanas; Basil S Lewis; Jose L Merino; Carlos Morillo; Jan Murin; Calambur Narasimhan; Ernesto Paolasso; Alexander Parkhomenko; Nicholas S Peters; Kui-Hian Sim; Martin K Stiles; Supachai Tanomsup; Lauri Toivonen; János Tomcsányi; Christian Torp-Pedersen; Hung-Fat Tse; Panos Vardas; Dragos Vinereanu; Denis Xavier; Wei Jun Zhu; Jun-Ren Zhu; Lydie Baret-Cormel; PALLAS Investigators; Jørgen Lykke Jeppesen

doi:http://dx.doi.org/10.1056/NEJMoa1109867

Dronedarone in high-risk permanent atrial fibrillation

Stuart J Connolly, A John Camm, Jonathan L Halperin, Campbell Joyner, Marco Alings, John Amerena, Dan Atar, Álvaro Avezum, Per Blomström, Martin Borggrefe, Andrzej Budaj, Shih-Ann Chen, Chi Keong Ching, Patrick Commerford, Antonio Dans, Jean-Marc Davy, Etienne Delacrétaz, Giuseppe Di Pasquale, Rafael Diaz, Paul DorianGreg Flaker, Sergey Golitsyn, Antonio Gonzalez-Hermosillo, Christopher B Granger, Hein Heidbüchel, Josef Kautzner, June Soo Kim, Fernando Lanas, Basil S Lewis, Jose L Merino, Carlos Morillo, Jan Murin, Calambur Narasimhan, Ernesto Paolasso, Alexander Parkhomenko, Nicholas S Peters, Kui-Hian Sim, Martin K Stiles, Supachai Tanomsup, Lauri Toivonen, János Tomcsányi, Christian Torp-Pedersen, Hung-Fat Tse, Panos Vardas, Dragos Vinereanu, Denis Xavier, Wei Jun Zhu, Jun-Ren Zhu, Lydie Baret-Cormel, PALLAS Investigators, Jørgen Lykke Jeppesen

471 Citationer (Scopus)

Abstract

BACKGROUND: Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. METHODS: We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. RESULTS: After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P = 0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P = 0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P = 0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P = 0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P = 0.02). CONCLUSIONS: Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.)

Originalsprog	Engelsk
Tidsskrift	New England Journal of Medicine
Vol/bind	365
Udgave nummer	24
Sider (fra-til)	2268-76
Antal sider	9
ISSN	0028-4793
DOI	https://doi.org/10.1056/NEJMoa1109867
Status	Udgivet - 15 dec. 2011

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http://dx.doi.org/10.1056/NEJMoa1109867

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Connolly, S. J., Camm, A. J., Halperin, J. L., Joyner, C., Alings, M., Amerena, J., Atar, D., Avezum, Á., Blomström, P., Borggrefe, M., Budaj, A., Chen, S-A., Ching, C. K., Commerford, P., Dans, A., Davy, J-M., Delacrétaz, E., Di Pasquale, G., Diaz, R., ... Jeppesen, J. L. (2011). Dronedarone in high-risk permanent atrial fibrillation. New England Journal of Medicine, 365(24), 2268-76. https://doi.org/10.1056/NEJMoa1109867

Connolly, SJ, Camm, AJ, Halperin, JL, Joyner, C, Alings, M, Amerena, J, Atar, D, Avezum, Á, Blomström, P, Borggrefe, M, Budaj, A, Chen, S-A, Ching, CK, Commerford, P, Dans, A, Davy, J-M, Delacrétaz, E, Di Pasquale, G, Diaz, R, Dorian, P, Flaker, G, Golitsyn, S, Gonzalez-Hermosillo, A, Granger, CB, Heidbüchel, H, Kautzner, J, Kim, JS, Lanas, F, Lewis, BS, Merino, JL, Morillo, C, Murin, J, Narasimhan, C, Paolasso, E, Parkhomenko, A, Peters, NS, Sim, K-H, Stiles, MK, Tanomsup, S, Toivonen, L, Tomcsányi, J, Torp-Pedersen, C, Tse, H-F, Vardas, P, Vinereanu, D, Xavier, D, Zhu, WJ, Zhu, J-R, Baret-Cormel, L, PALLAS Investigators & Jeppesen, JL 2011, 'Dronedarone in high-risk permanent atrial fibrillation', New England Journal of Medicine, bind 365, nr. 24, s. 2268-76. https://doi.org/10.1056/NEJMoa1109867

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title = "Dronedarone in high-risk permanent atrial fibrillation",

abstract = "BACKGROUND: Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. METHODS: We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. RESULTS: After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P = 0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P = 0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P = 0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P = 0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P = 0.02). CONCLUSIONS: Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.)",

author = "Connolly, {Stuart J} and Camm, {A John} and Halperin, {Jonathan L} and Campbell Joyner and Marco Alings and John Amerena and Dan Atar and {\'A}lvaro Avezum and Per Blomstr{\"o}m and Martin Borggrefe and Andrzej Budaj and Shih-Ann Chen and Ching, {Chi Keong} and Patrick Commerford and Antonio Dans and Jean-Marc Davy and Etienne Delacr{\'e}taz and {Di Pasquale}, Giuseppe and Rafael Diaz and Paul Dorian and Greg Flaker and Sergey Golitsyn and Antonio Gonzalez-Hermosillo and Granger, {Christopher B} and Hein Heidb{\"u}chel and Josef Kautzner and Kim, {June Soo} and Fernando Lanas and Lewis, {Basil S} and Merino, {Jose L} and Carlos Morillo and Jan Murin and Calambur Narasimhan and Ernesto Paolasso and Alexander Parkhomenko and Peters, {Nicholas S} and Kui-Hian Sim and Stiles, {Martin K} and Supachai Tanomsup and Lauri Toivonen and J{\'a}nos Tomcs{\'a}nyi and Christian Torp-Pedersen and Hung-Fat Tse and Panos Vardas and Dragos Vinereanu and Denis Xavier and Zhu, {Wei Jun} and Jun-Ren Zhu and Lydie Baret-Cormel and Torp-Pedersen, {Christian Tobias} and Jeppesen, {J{\o}rgen Lykke}",

note = "J{\o}rgen Lykke Jeppesen er collaborator",

year = "2011",

month = dec,

day = "15",

doi = "http://dx.doi.org/10.1056/NEJMoa1109867",

language = "English",

volume = "365",

pages = "2268--76",

journal = "New England Journal of Medicine",

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TY - JOUR

T1 - Dronedarone in high-risk permanent atrial fibrillation

AU - Connolly, Stuart J

AU - Camm, A John

AU - Halperin, Jonathan L

AU - Joyner, Campbell

AU - Alings, Marco

AU - Amerena, John

AU - Atar, Dan

AU - Avezum, Álvaro

AU - Blomström, Per

AU - Borggrefe, Martin

AU - Budaj, Andrzej

AU - Chen, Shih-Ann

AU - Ching, Chi Keong

AU - Commerford, Patrick

AU - Dans, Antonio

AU - Davy, Jean-Marc

AU - Delacrétaz, Etienne

AU - Di Pasquale, Giuseppe

AU - Diaz, Rafael

AU - Dorian, Paul

AU - Flaker, Greg

AU - Golitsyn, Sergey

AU - Gonzalez-Hermosillo, Antonio

AU - Granger, Christopher B

AU - Heidbüchel, Hein

AU - Kautzner, Josef

AU - Kim, June Soo

AU - Lanas, Fernando

AU - Lewis, Basil S

AU - Merino, Jose L

AU - Morillo, Carlos

AU - Murin, Jan

AU - Narasimhan, Calambur

AU - Paolasso, Ernesto

AU - Parkhomenko, Alexander

AU - Peters, Nicholas S

AU - Sim, Kui-Hian

AU - Stiles, Martin K

AU - Tanomsup, Supachai

AU - Toivonen, Lauri

AU - Tomcsányi, János

AU - Torp-Pedersen, Christian

AU - Tse, Hung-Fat

AU - Vardas, Panos

AU - Vinereanu, Dragos

AU - Xavier, Denis

AU - Zhu, Wei Jun

AU - Zhu, Jun-Ren

AU - Baret-Cormel, Lydie

AU - PALLAS Investigators

AU - Jeppesen, Jørgen Lykke

N1 - Jørgen Lykke Jeppesen er collaborator

PY - 2011/12/15

Y1 - 2011/12/15

N2 - BACKGROUND: Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. METHODS: We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. RESULTS: After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P = 0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P = 0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P = 0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P = 0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P = 0.02). CONCLUSIONS: Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.)

AB - BACKGROUND: Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. METHODS: We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. RESULTS: After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P = 0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P = 0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P = 0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P = 0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P = 0.02). CONCLUSIONS: Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.)

U2 - http://dx.doi.org/10.1056/NEJMoa1109867

DO - http://dx.doi.org/10.1056/NEJMoa1109867

M3 - Journal article

SN - 0028-4793

VL - 365

SP - 2268

EP - 2276

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 24

ER -

Dronedarone in high-risk permanent atrial fibrillation

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