Lazzerini Pietro Enea, Bertolozzi Iacopo, Acampa Maurizio, Cantara Silvia, Castagna Maria Grazia, Pieragnoli Laura, D'Errico Antonio, Rossi Marco, Bisogno Stefania, El-Sherif Nabil, Boutjdir Mohamed, Laghi-Pasini Franco, Capecchi Pier Leopoldo
Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.
Cardiology Intensive Therapy Unit, Department of Internal Medicine, Nuovo Ospedale San Giovanni di Dio, Florence, Italy.
Front Pharmacol. 2020 May 13;11:684. doi: 10.3389/fphar.2020.00684. eCollection 2020.
Men normally have shorter heart rate-corrected QT interval (QTc) than women, at least in part due to accelerating effects of testosterone on ventricular repolarization. Accumulating data suggest that androgen-deprivation therapy (ADT) used for the treatment of prostatic cancer, may increase Torsades de Pointes (TdP) risk by prolonging QTc. However, the evidence for such an association is currently limited to few case reports, in most cases deriving from the analysis of uncontrolled sources such as pharmacovigilance databases.
To better determine the clinical impact of ADT on TdP development, we examined the prevalence of this therapy in a consecutive cohort of 66 TdP patients, prospectively collected over a ~10 years period.
We found and described four patients who were under ADT for prostatic cancer when TdP occurred, and in two cases degenerated to cardiac arrest. Notably, in this unselected population, ADTs unexpectedly represented the second most frequently administered QT-prolonging medication in males (4/24, 17%), after amiodarone. Moreover, in the ADT patients, a blood withdrawal was performed within 24 h from TdP/marked QTc prolongation occurrence and circulating concentration of androgens and gonadothropins were measured. As expected, all cases showed markedly reduced testosterone levels (total, free, and available).
We provide evidence that a significant proportion of patients developing TdP were under treatment with ADT for prostatic cancer, thus confirming the clinical relevance of previous pharmacovigilance signals. An accurate assessment of the arrhythmic risk profile should be included in the standard of care of prostatic cancer patients before starting ADT.
男性通常比女性的心率校正QT间期（QTc）短，至少部分原因是睾酮对心室复极有加速作用。越来越多的数据表明，用于治疗前列腺癌的雄激素剥夺疗法（ADT）可能会通过延长QTc增加尖端扭转型室速（TdP）的风险。然而，这种关联的证据目前仅限于少数病例报告，大多数病例来自对诸如药物警戒数据库等非对照来源的分析。
为了更好地确定ADT对TdP发生的临床影响，我们在一个连续队列中检查了66例TdP患者中这种疗法的患病率，这些患者是在约10年期间前瞻性收集的。
我们发现并描述了4例在发生TdP时正在接受前列腺癌ADT治疗的患者，其中2例发展为心脏骤停。值得注意的是，在这个未经过筛选的人群中，ADT意外地成为男性中第二常用的可延长QT的药物（4/24，17%），仅次于胺碘酮。此外，在ADT患者中，在TdP/明显QTc延长发生后的24小时内进行了采血，并测量了雄激素和促性腺激素的循环浓度。正如预期的那样，所有病例的睾酮水平（总睾酮、游离睾酮和可利用睾酮）均显著降低。
我们提供的证据表明，相当一部分发生TdP的患者正在接受前列腺癌ADT治疗，从而证实了先前药物警戒信号的临床相关性。在开始ADT之前，前列腺癌患者的标准治疗应包括对心律失常风险概况的准确评估。
