| アブストラクト | AIMS: With the explosion of anticancer drugs, an emerging concern is the risk for drug-induced sudden death (SD) via ventricular arrhythmias (VA). METHODS AND RESULTS: We used the international pharmacovigilance database VigiBase (n = 18 441 659 reports) to compare drug-induced long QT (diLQT, n = 18 123) and VA (n = 29 193) including torsade de pointes (TdP, n = 8163) reporting for 663 anticancer drugs vs. all other drugs until 01/01/2019. The analysis used the 95% lower-end credibility interval of the information component (IC025), an indicator for disproportionate Bayesian reporting; significant when IC025 >0. There were 2301 reports (13.8% fatal) for 40 anticancer drugs significantly associated with diLQT (with 27 also associated with VA or SD) and 9 drugs associated with VA without diLQT. Half of these (46.9%, 23/49) were associated with SD. Most (41%, 20/49) were kinase inhibitors, 8% (4/49) were hormonal therapies, 6% (3/49) were immunotherapies, 24% (12/49) were cytotoxics, and 20% (10/49) were miscellaneous. In VigiBase, reports of diLQT, TdP, or VA increased from 580 in the period 1967-83 to 15 070 in 2014-18 with the proportion related to anticancer drugs increasing from 0.9% (5/580) to 14.0% (2115/15 070) (P < 0.0001). Concordance between these VigiBase signals and data concerning diLQT and VA/TdP identified in CredibleMeds or US Food and Drug Administration (FDA) labels was moderate (kappa = 0.47 and 0.40, P < 0.0001). Twenty-three drugs represent new signals, while 24 flagged by CredibleMeds or FDA had no signal in VigiBase. A three-level SD risk stratification relying on isolated long QT (low risk), associated with VA without SD (moderate risk), and VA with SD (high risk) is proposed. CONCLUSION: This list of liable anticancer drugs may prove useful for physicians and regulatory authorities to re-evaluate cardiac monitoring requirements. CLINICAL TRIAL REGISTRATION: NCT03530215. |
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| 投稿者 | Salem, Joe-Elie; Nguyen, Lee S; Moslehi, Javid J; Ederhy, Stephane; Lebrun-Vignes, Benedicte; Roden, Dan M; Funck-Brentano, Christian; Gougis, Paul |
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| 組織名 | INSERM, CIC-1901, Sorbonne Universite, AP-HP, Pitie-Salpetriere Hospital,;Department of Pharmacology, CLIP(2) Galilee, Regional Pharmacovigilance Center,;UNICO-GRECO Cardio-Oncology Program, Paris 75013, France.;Cardio-Oncology Program, Department of Medicine and Pharmacology, Vanderbilt;University Medical Center, Nashville, TN, USA.;Research & Innovation of CMC Ambroise Pare, Neuilly-sur-Seine 92200, France.;INSERM, Sorbonne Universite, Department of Cardiology, AP-HP, Saint Antoine;Hospital, UNICO-GRECO Cardio-oncology program, Paris, France.;UPEC EA EpiDermE, 7379, France.;Department of Biomedical Informatics, Vanderbilt University Medical Center,;Nashville, TN, USA. |
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