| アブストラクト | BACKGROUND: 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. AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. |
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| ジャーナル名 | Archives of cardiovascular diseases |
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| 投稿日 | 2019/11/7 |
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| 投稿者 | Bretagne, Marie; Lebrun-Vignes, Benedicte; Pariente, Antoine; Shaffer, Christian M; Malouf, Gabriel G; Dureau, Pauline; Potey, Camille; Funck-Brentano, Christian; Roden, Dan M; Moslehi, Javid J; Salem, Joe-Elie |
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| 組織名 | Department of pharmacology, Sorbonne universite, Inserm CIC Paris-Est, ICAN,;UNICO-GRECO, Sorbonne Cardio-Oncology program, regional pharmacovigilance centre,;Pitie-Salpetriere hospital, AP-HP, 75013 Paris, France.;Pharmacoepidemiology Team, department of pharmacology, universite de Bordeaux,;CHU de Bordeaux, Inserm, CIC-1401, Bordeaux population health research centre,;UMR 1219, 33076 Bordeaux, France.;Departments of medicine, pharmacology and biomedical informatics, Vanderbilt;university medical center, 37232 Nashville, TN, USA.;Department of haematology and medical oncology, hopital civil, CHRU de;Strasbourg, 67000 Strasbourg, France.;Regional pharmacovigilance centre, department of pharmacology, 59000 Lille,;France.;Cardio-oncology program, department of medicine and pharmacology, Vanderbilt;Pitie-Salpetriere hospital, AP-HP, 75013 Paris, France; Cardio-oncology program,;department of medicine and pharmacology, Vanderbilt university medical center,;37232 Nashville, TN, USA. Electronic address: joe-elie.salem@aphp.fr. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/31685432/ |
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