静脈再極化に対するアンドロゲン効果:国際医薬品監視データベースからiPSC心筋細胞へのトランスレーション研究
Joe-Elie Salem1,2,3, Tao Yang2,3, Javid J Moslehi2
1Assitance Publique Hopitaux de Paris, Pitié-Salpêtriére Hospital, Departments of Pharmacology and Cardiology, UNICO-GRECO Cardio-oncology Program, Centre d'investigation clinique-1421, Pharmacovigilance Unit (J-E.S., X.W., E.G., F.H-L., B.L-V., C.F-B.), INSERM, Sorbonne Université, Paris, France.
Circulation
|August 6, 2019
まとめ
アンドロゲン欠乏療法 (ADT) は,男性における長QT症候群 (aLQTS) とTorsades de pointes (TdP) のリスクを高めます. 幹細胞モデルでは,ADTであるエンザルウタミドが心臓病およびQT間隔の延長と有意な関連性を示した.
科学分野:
- 心臓病科
- 薬理学について
- 電気生理学
背景:
- 男性のヒポゴナジズムとアンドロゲン欠乏療法 (ADT) は,得られた長QT症候群 (aLQTS) とTorsades de pointes (TdP) と関連しています.
- ADTに関連したaLQTSの臨床的特徴とメカニズムについては,さらなる解明が必要である.
研究 の 目的:
- aLQTSとTdPのような心律不整症との関連を調査する.
- ADT誘発の心臓病の原因となる 電気生理学的メカニズムを探る
主な方法:
- ADTに関連した有害事象を VigiBase 製薬警戒データベースで検索しました.
- 誘導された多能幹細胞由来心筋細胞を用いて,ADTとジヒドロテストステロンの電気生理学的効果を研究した.
主要な成果:
- VigiBaseでは,aLQTSおよび/またはTdPの184例と,ADTに関連した突然死亡の99例を特定しました.
- 検査された10のADTのうち7のADTは心疾患との不均衡な関連を示し,エンザルタミドはより高い死亡率と関連していた.
- エンザルウタミドは有効期間を大幅に延長し,デポラライゼーションを誘発し,カリウム電流を抑制し,ナトリウム電流を増加させ,ジヒドロテストステロンによって効果は逆転した.
結論:
- QT延長とTdPは,エンザルタミドや他のADT治療を受けている男性にとって重大なリスクです.
- この結果は,ADTを投与する患者の心臓の注意深いモニタリングの必要性を強調しています.
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