RT Journal Article
SR Electronic
T1 Increased long QT and torsade de pointes reporting on tamoxifen compared with aromatase inhibitors
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP 1859
OP 1863
DO 10.1136/heartjnl-2017-312934
VO 104
IS 22
A1 Virginie Grouthier
A1 Benedicte Lebrun-Vignes
A1 Andrew M Glazer
A1 Philippe Touraine
A1 Christian Funck-Brentano
A1 Antoine Pariente
A1 Carine Courtillot
A1 Anne Bachelot
A1 Dan M Roden
A1 Javid J Moslehi
A1 Joe-Elie Salem
YR 2018
UL http://heart.bmj.com/content/104/22/1859.abstract
AB 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.