Amiodarone treatment in atrial fibrillation and the risk of incident cancers: a nationwide observational study

Peter Vibe Rasmussen, Frederik Dalgaard, Gunnar Hilmar Gislason, Christian Torp-Pedersen, Jonathan Piccini, Maria D'Souza, Martin H Ruwald, Jannik Langtved Pallisgaard, Morten Lock Hansen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND: In observational studies, case reports, and animal studies, amiodarone has been associated with incident cancer.

OBJECTIVES: To examine whether a dose-response relationship between the use of amiodarone and the risk of cancer could be ascertained in a large nationwide study cohort.

METHODS: Using nationwide registers, we included all Danish patients with atrial fibrillation (AF) treated with amiodarone from 1996 to 2014. Exposure was defined both by categories and as a continuous variable of the cumulative defined daily doses (cDDD) of amiodarone. The association between amiodarone cDDD and incident cancer, as well as organ-specific types of cancer (skin, liver, lung), were estimated using multivariable Cox regression models and reported as hazard ratios (HR) with 95% Confidence Intervals (CI) and using cubic restricted spline plots.

RESULTS: We included 18,503 patients with a median follow-up time of 8.1 years (Interquartile Range [IQR] 4.3 - 12.4). Median age was 70 years (IQR 63-77). A total of 2974 individuals developed cancer during follow-up. We found no associations between increasing amiodarone exposure (cDDD 181-400 & cDDD >400) and the hazard of incident cancer (HR 0.95, 95% CI 0.87 - 1.04 & HR 1.01, 95% CI 0.92 - 1.10) with reference to patients with a cDDD < 181. When investigating specific cancer types (skin, liver, and lung), as well as cDDD as a continuous variable, similar results were found.

CONCLUSIONS: In a large nationwide cohort of AF patients treated with amiodarone, we found no evidence of a dose-response relationship between cumulative dose of amiodarone and incident cancer risk.

Original languageEnglish
JournalHeart Rhythm
ISSN1547-5271
DOIs
Publication statusE-pub ahead of print - 29 Nov 2019

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Amiodarone
Atrial Fibrillation
Observational Studies
Neoplasms
Skin Neoplasms
Confidence Intervals
Therapeutics
Liver Neoplasms
Proportional Hazards Models
Lung Neoplasms
Cohort Studies
Lung

Cite this

Rasmussen, Peter Vibe ; Dalgaard, Frederik ; Gislason, Gunnar Hilmar ; Torp-Pedersen, Christian ; Piccini, Jonathan ; D'Souza, Maria ; Ruwald, Martin H ; Pallisgaard, Jannik Langtved ; Hansen, Morten Lock. / Amiodarone treatment in atrial fibrillation and the risk of incident cancers : a nationwide observational study. In: Heart Rhythm. 2019.
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title = "Amiodarone treatment in atrial fibrillation and the risk of incident cancers: a nationwide observational study",
abstract = "BACKGROUND: In observational studies, case reports, and animal studies, amiodarone has been associated with incident cancer.OBJECTIVES: To examine whether a dose-response relationship between the use of amiodarone and the risk of cancer could be ascertained in a large nationwide study cohort.METHODS: Using nationwide registers, we included all Danish patients with atrial fibrillation (AF) treated with amiodarone from 1996 to 2014. Exposure was defined both by categories and as a continuous variable of the cumulative defined daily doses (cDDD) of amiodarone. The association between amiodarone cDDD and incident cancer, as well as organ-specific types of cancer (skin, liver, lung), were estimated using multivariable Cox regression models and reported as hazard ratios (HR) with 95{\%} Confidence Intervals (CI) and using cubic restricted spline plots.RESULTS: We included 18,503 patients with a median follow-up time of 8.1 years (Interquartile Range [IQR] 4.3 - 12.4). Median age was 70 years (IQR 63-77). A total of 2974 individuals developed cancer during follow-up. We found no associations between increasing amiodarone exposure (cDDD 181-400 & cDDD >400) and the hazard of incident cancer (HR 0.95, 95{\%} CI 0.87 - 1.04 & HR 1.01, 95{\%} CI 0.92 - 1.10) with reference to patients with a cDDD < 181. When investigating specific cancer types (skin, liver, and lung), as well as cDDD as a continuous variable, similar results were found.CONCLUSIONS: In a large nationwide cohort of AF patients treated with amiodarone, we found no evidence of a dose-response relationship between cumulative dose of amiodarone and incident cancer risk.",
author = "Rasmussen, {Peter Vibe} and Frederik Dalgaard and Gislason, {Gunnar Hilmar} and Christian Torp-Pedersen and Jonathan Piccini and Maria D'Souza and Ruwald, {Martin H} and Pallisgaard, {Jannik Langtved} and Hansen, {Morten Lock}",
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doi = "10.1016/j.hrthm.2019.11.025",
language = "English",
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Amiodarone treatment in atrial fibrillation and the risk of incident cancers : a nationwide observational study. / Rasmussen, Peter Vibe; Dalgaard, Frederik; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian; Piccini, Jonathan; D'Souza, Maria; Ruwald, Martin H; Pallisgaard, Jannik Langtved; Hansen, Morten Lock.

In: Heart Rhythm, 29.11.2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Amiodarone treatment in atrial fibrillation and the risk of incident cancers

T2 - a nationwide observational study

AU - Rasmussen, Peter Vibe

AU - Dalgaard, Frederik

AU - Gislason, Gunnar Hilmar

AU - Torp-Pedersen, Christian

AU - Piccini, Jonathan

AU - D'Souza, Maria

AU - Ruwald, Martin H

AU - Pallisgaard, Jannik Langtved

AU - Hansen, Morten Lock

PY - 2019/11/29

Y1 - 2019/11/29

N2 - BACKGROUND: In observational studies, case reports, and animal studies, amiodarone has been associated with incident cancer.OBJECTIVES: To examine whether a dose-response relationship between the use of amiodarone and the risk of cancer could be ascertained in a large nationwide study cohort.METHODS: Using nationwide registers, we included all Danish patients with atrial fibrillation (AF) treated with amiodarone from 1996 to 2014. Exposure was defined both by categories and as a continuous variable of the cumulative defined daily doses (cDDD) of amiodarone. The association between amiodarone cDDD and incident cancer, as well as organ-specific types of cancer (skin, liver, lung), were estimated using multivariable Cox regression models and reported as hazard ratios (HR) with 95% Confidence Intervals (CI) and using cubic restricted spline plots.RESULTS: We included 18,503 patients with a median follow-up time of 8.1 years (Interquartile Range [IQR] 4.3 - 12.4). Median age was 70 years (IQR 63-77). A total of 2974 individuals developed cancer during follow-up. We found no associations between increasing amiodarone exposure (cDDD 181-400 & cDDD >400) and the hazard of incident cancer (HR 0.95, 95% CI 0.87 - 1.04 & HR 1.01, 95% CI 0.92 - 1.10) with reference to patients with a cDDD < 181. When investigating specific cancer types (skin, liver, and lung), as well as cDDD as a continuous variable, similar results were found.CONCLUSIONS: In a large nationwide cohort of AF patients treated with amiodarone, we found no evidence of a dose-response relationship between cumulative dose of amiodarone and incident cancer risk.

AB - BACKGROUND: In observational studies, case reports, and animal studies, amiodarone has been associated with incident cancer.OBJECTIVES: To examine whether a dose-response relationship between the use of amiodarone and the risk of cancer could be ascertained in a large nationwide study cohort.METHODS: Using nationwide registers, we included all Danish patients with atrial fibrillation (AF) treated with amiodarone from 1996 to 2014. Exposure was defined both by categories and as a continuous variable of the cumulative defined daily doses (cDDD) of amiodarone. The association between amiodarone cDDD and incident cancer, as well as organ-specific types of cancer (skin, liver, lung), were estimated using multivariable Cox regression models and reported as hazard ratios (HR) with 95% Confidence Intervals (CI) and using cubic restricted spline plots.RESULTS: We included 18,503 patients with a median follow-up time of 8.1 years (Interquartile Range [IQR] 4.3 - 12.4). Median age was 70 years (IQR 63-77). A total of 2974 individuals developed cancer during follow-up. We found no associations between increasing amiodarone exposure (cDDD 181-400 & cDDD >400) and the hazard of incident cancer (HR 0.95, 95% CI 0.87 - 1.04 & HR 1.01, 95% CI 0.92 - 1.10) with reference to patients with a cDDD < 181. When investigating specific cancer types (skin, liver, and lung), as well as cDDD as a continuous variable, similar results were found.CONCLUSIONS: In a large nationwide cohort of AF patients treated with amiodarone, we found no evidence of a dose-response relationship between cumulative dose of amiodarone and incident cancer risk.

U2 - 10.1016/j.hrthm.2019.11.025

DO - 10.1016/j.hrthm.2019.11.025

M3 - Journal article

C2 - 31790830

JO - Heart Rhythm

JF - Heart Rhythm

SN - 1547-5271

ER -