Grouthier Virginie, Lebrun-Vignes Benedicte, Glazer Andrew M, Touraine Philippe, Funck-Brentano Christian, Pariente Antoine, Courtillot Carine, Bachelot Anne, Roden Dan M, Moslehi Javid J, Salem Joe-Elie
Department of Endocrinology and Reproductive Medicine, Sorbonne Universités, AP-HP, Pitié-Salpêtrière Hospital, Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Centre de Référence des Pathologies Gynécologiques Rares, Paris, France.
AP-HP, Pitié-Salpêtrière Hospital Department of Pharmacology CIC-1421 Pharmacovigilance Unit INSERM UMR ICAN 1166 Sorbonne Université UPMC, Univ Paris 06, Institute of CArdiometabolism and Nutrition (ICAN), Paris, France.
Heart. 2018 Nov;104(22):1859-1863. doi: 10.1136/heartjnl-2017-312934. Epub 2018 May 2.
A prolonged QTc (LQT) is a surrogate for the risk of torsade de pointes (TdP). QTc interval duration is influenced by sex hormones: oestradiol prolongs and testosterone shortens QTc. Drugs used in the treatment of breast cancer have divergent effects on hormonal status.
We performed a disproportionality analysis using the European database of suspected adverse drug reaction (ADR) reports to evaluate the reporting OR (ROR χ) of LQT, TdP and ventricular arrhythmias associated with selective oestrogen receptor modulators (SERMs: tamoxifen and toremifene) as opposed to aromatase inhibitors (AIs: anastrozole, exemestane and letrozole). When the proportion of an ADR is greater in patients exposed to a drug (SERMs) compared with patients exposed to control drug (AIs), this suggests an association between the specific drug and the reaction and is a potential signal for safety. Clinical and demographic characterisation of patients with SERMs-induced LQT and ventricular arrhythmias was performed.
SERMs were associated with higher proportion of LQT reports versus AIs (26/8318 vs 11/14851, ROR: 4.2 (2.11-8.55), p<0.001). SERMs were also associated with higher proportion of TdP and ventricular arrhythmia reports versus AIs (6/8318 vs 2/14851, ROR: 5.4 (1.29-26.15), p:0.02; 16/8318 vs 12/14851, ROR: 2.38 (1.15-4.94), p:0.02, respectively). Mortality was 38% in patients presenting ventricular arrhythmias associated with SERMs.
SERMs are associated with more reports of drug-induced LQT, TdP and ventricular arrhythmias compared with AIs. This finding is consistent with oestradiol-like properties of SERMs on the heart as opposed to effects of oestrogen deprivation and testosterone increase induced by AIs.
NCT03259711.
QTc间期延长（长QT综合征，LQT）是尖端扭转型室性心动过速（TdP）风险的一个替代指标。QTc间期持续时间受性激素影响：雌二醇会延长QTc，而睾酮会缩短QTc。用于治疗乳腺癌的药物对激素状态有不同影响。
我们使用欧洲疑似药物不良反应（ADR）报告数据库进行了不成比例分析，以评估与选择性雌激素受体调节剂（SERMs：他莫昔芬和托瑞米芬）相比，芳香化酶抑制剂（AIs：阿那曲唑、依西美坦和来曲唑）相关的LQT、TdP和室性心律失常的报告比值比（ROR χ）。当暴露于一种药物（SERMs）的患者中某种ADR的比例高于暴露于对照药物（AIs）的患者时，这表明该特定药物与该反应之间存在关联，并且是一个潜在的安全信号。对SERMs诱导的LQT和室性心律失常患者进行了临床和人口统计学特征分析。
与AIs相比，SERMs相关的LQT报告比例更高（26/8318 vs 11/14851，ROR：4.2（2.11 - 8.55），p<0.001）。与AIs相比，SERMs相关的TdP和室性心律失常报告比例也更高（6/8318 vs 2/14851，ROR：5.4（1.29 - 26.15），p：0.02；16/8318 vs 12/14851，ROR：2.38（1.15 - 4.94），p：0.02）。与SERMs相关的室性心律失常患者的死亡率为38%。
与AIs相比，SERMs相关的药物诱导LQT、TdP和室性心律失常报告更多。这一发现与SERMs对心脏具有类似雌二醇的特性一致，与AIs诱导的雌激素剥夺和睾酮增加的作用相反。
NCT03259711。
