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Archives of cardiovascular diseases
Sous presse. Epreuves corrigées par l'auteur. Disponible en ligne depuis le mercredi 6 novembre 2019
Doi : 10.1016/j.acvd.2019.09.006
Received : 10 May 2019 ;  accepted : 9 September 2019
Heart failure and atrial tachyarrhythmia on abiraterone: A pharmacovigilance study
Tachyarythmie supraventriculaire et insuffisance cardiaque sous abiratérone : une étude de pharmacovigilance

Marie Bretagne a, Bénédicte Lebrun-Vignes a, Antoine Pariente b, Christian M. Shaffer c, Gabriel G. Malouf d, Pauline Dureau a, Camille Potey e, Christian Funck-Brentano a, Dan M. Roden c, Javid J. Moslehi f, Joe-Elie Salem a, f,
a Department of pharmacology, Sorbonne université, Inserm CIC Paris-Est, ICAN, UNICO-GRECO, Sorbonne Cardio-Oncology program, regional pharmacovigilance centre, Pitié-Salpêtrière hospital, AP–HP, 75013 Paris, France 
b Pharmacoepidemiology Team, department of pharmacology, université de Bordeaux, CHU de Bordeaux, Inserm, CIC-1401, Bordeaux population health research centre, UMR 1219, 33076 Bordeaux, France 
c Departments of medicine, pharmacology and biomedical informatics, Vanderbilt university medical center, 37232 Nashville, TN, USA 
d Department of haematology and medical oncology, hôpital civil, CHRU de Strasbourg, 67000 Strasbourg, France 
e Regional pharmacovigilance centre, department of pharmacology, 59000 Lille, France 
f Cardio-oncology program, department of medicine and pharmacology, Vanderbilt university medical center, 37232 Nashville, TN, USA 

Corresponding author at: Centre d’investigation clinique Paris-Est, hôpital La Pitié-Salpêtrière, 47-83, boulevard de l’Hôpital, 75651 Paris cedex 13, France.Centre d’investigation clinique Paris-Est, hôpital La Pitié-Salpêtrière47-83, boulevard de l’HôpitalParis cedex 1375651France

Abiraterone and enzalutamide are recently-approved androgen deprivation therapies (ADTs) for metastatic prostate cancer, with unknown cardiac safety profiles. Abiraterone has a propensity to hypermineralocorticism on top of androgen deprivation, so might carry an additional risk for atrial tachyarrhythmia (AT) and heart failure (HF) compared with other ADTs.


To determine if abiraterone was associated with an increased proportion of AT and HF reports among all suspected adverse drug reactions (ADRs) reported in several pharmacovigilance databases compared with enzalutamide, other ADTs and all other drugs.


In this observational retrospective pharmacovigilance study, we performed a disproportionality analysis of reports of suspected ADRs in men in the French pharmacovigilance database, the European pharmacovigilance database and the international pharmacovigilance database VigiBase, to evaluate the reporting odds ratios (RORs) of AT and HF for abiraterone compared with enzalutamide, other ADTs and all other drugs.


In the 5,759,781 ADR reports in men in VigiBase, 55,070 pertained to ADTs. The RORs for AT for abiraterone versus enzalutamide, other ADTs and all other drugs were 4.1 (95% confidence interval 3.1–5.3), 3.7 (3–4.5) and 3.2 (2.7–3.7), respectively (P <0.0001 for all). The corresponding RORs for HF were 2.5 (2–3), 1.5 (1.3–1.7) and 2 (1.7–2.3), respectively (P <0.0001 for all). These results were concordant with the French and European pharmacovigilance databases. Mean times to AT and HF onset were shorter with abiraterone (5.2±0.8 and 4.5±0.6 months, respectively) versus other ADTs (13.3±3.2 and 9.2±1.1 months, respectively) (both P <0.05). Cases on abiraterone versus other ADTs were more frequently associated with at least two ADR terms, including AT, HF, hypokalaemia, hypertension and oedema (13.6% vs 6%; P <0.0001). For abiraterone, age, but not dose, was associated with reporting of AT and HF versus any other ADR.


Compared with other ADTs, abiraterone was associated with higher reporting of AT and HF, associated with hypokalaemia, hypertension and oedema. These findings are consistent with the hypermineralocorticism induced by abiraterone, but not by other ADTs.

The full text of this article is available in PDF format.

L’abiratérone et l’enzalutamide sont deux traitements anti-androgènes (AA) utilisés dans le traitement des cancers prostatiques métastatiques. Leur profil de tolérance cardiovasculaire est peu connu. L’abiratérone est responsable d’un hyper-minéralocorticisme, qui pourrait entraîner un risque supplémentaire de tachyarythmie supraventriculaire (TSV) et d’insuffisance cardiaque (IC).


Étudier s’il existe une disproportionnalité du nombre de cas rapportés de TSV et d’IC par rapport aux taux globaux d’évènements indésirables (EI) chez les patients traités par abiratérone versus (vs) enzalutamide, vs les autres AA et vs l’ensemble des médicaments de la base.


Étude observationnelle, rétrospective, de disproportionnalité avec calcul du reporting odds-ratio (ROR), dans les bases de pharmacovigilance française, européenne et mondiale (VigiBase).


Parmi les 5 759 781 EI déclarés chez des hommes dans VigiBase, 55 070 concernaient les médicaments AA étudiés. Le ROR pour les TSV associées à l’abiratérone était de 3,2 [2,7–3,7] vs enzalutamide, de 3,7 [3–4,5] vs les autres AA et de 3,2 [2,7–3,7] vs l’ensemble de la base (p <0,0001 pour tous). Le ROR pour les IC était de 2,5 [2–3], de 1,5 [1,3–1,7] et de 2 [1,7–2,3], respectivement (p <0,0001 pour tous). Les délais moyens d’apparition des TSV et des IC étaient plus court pour l’abiratérone (5,2±0,8 et 4,5±0,6 mois, respectivement) que pour les autres AA (13,3±3,2 et 9,2±1,1 mois ; p <0,05). Par rapport aux autres AA, les EI déclarés avec l’abiratérone comprenaient plus fréquemment2 EI à type de TSV, IC, hypokaliémie, hypertension et œdème (13,6 % vs 6 %, p <0,0001).


L’abiratérone, responsable d’un hyper-minéralocorticisme, présente une proportion plus élevée de cas rapportés de TSV et d’IC, fréquemment associés à l’hypokaliémie, l’hypertension ou les œdèmes, comparé à l’enzalutamide et aux autres AA dans les bases de pharmacovigilance française, européenne et mondiale.

The full text of this article is available in PDF format.

Keywords : Abiraterone, Enzalutamide, Androgen deprivation therapy, Heart failure, Atrial fibrillation

Mots clés : Abiratérone, Enzalutamide, Anti-androgène, Insuffisance cardiaque, Fibrillation auriculaire

Abbreviations : ADR, ADT, AT, AT/HF, CI, HF, ISCR, ROR

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