Key result
Androgen deprivation therapy is linked to a ~6.8-fold higher risk of TdP in elderly men.
Why the study?
Evidence that androgen-deprivation therapy for prostatic cancer increases Torsades de Pointes risk by prolonging QTc has been limited to few case reports and uncontrolled pharmacovigilance databases.
What is the prevalence of androgen-deprivation therapy use among patients presenting with Torsades de Pointes?
Observational (n=66)
No
What is the prevalence of androgen-deprivation therapy use among patients presenting with Torsades de Pointes?
Relative Risk: 6.83 (95% CI 1.63–28.61)
Absolute Event Rate: 16.7% vs 2.4%
p-value: p=0.014
Androgen-deprivation therapy is a clinically significant contributor to Torsades de Pointes in men, highlighting the need for baseline arrhythmic risk assessment before initiating treatment for prostate cancer.
ADT may prolong QTc and raise TdP risk during prostate cancer treatment; leaves open need for controlled confirmation before practice change.
BACKGROUND: 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. OBJECTIVE: 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. METHODS AND RESULTS: 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). CONCLUSION: 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.
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Lazzerini et al. (2020) conducted an observational in Torsades de Pointes (n=66). Androgen deprivation therapy vs. No androgen deprivation therapy (control population of elderly males) was evaluated on Prevalence of androgen deprivation therapy use in males with TdP compared to control elderly males (RR 6.83, 95% CI 1.63-28.61, p=0.014). Androgen deprivation therapy was present in 17% of male patients developing Torsades de Pointes, representing a significantly higher prevalence compared to a control population of elderly males (RR 6.83).
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