Objective 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.
Methods We performed a disproportionality analysis using the European database of suspected adverse drug reaction (ADR) reports to evaluate the reporting OR (ROR χ2) 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.
Results 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.
Conclusions 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.
Trial registration number NCT03259711.
- Long QT syndrome
- torsade de pointes
- ventricular arrhythmias
- selective estrogen receptor modulators
- aromatase inhibitors
- sex steroid hormones
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Funding This study was supported by Philippe Foundation and Fondation Recherche Medicale “SPE20170336816”.
Disclaimer The information does not represent the opinion of the European Medicines Agency or World Health Organization.
Competing interests JJM (Consultant: Novartis,Pfizer, Bristol Myers Squibb, Takeda). The other authors have nothing to disclose.
Patient consent Not required.
Ethics approval The use of confidential electronically processed patient data was approved by the French National Commission for Data Protection and Liberties (Commission Nationale de l’Informatique et des Libertés; reference:1922081).
Provenance and peer review Not commissioned; externally peer reviewed.