PMID- 29720397
OWN - NLM
STAT- MEDLINE
DCOM- 20190314
LR  - 20190314
IS  - 1468-201X (Electronic)
IS  - 1355-6037 (Linking)
VI  - 104
IP  - 22
DP  - 2018 Nov
TI  - Increased long QT and torsade de pointes reporting on tamoxifen compared with
      aromatase inhibitors.
PG  - 1859-1863
LID - 10.1136/heartjnl-2017-312934 [doi]
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 chi(2)) 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.
CI  - (c) Article author(s) (or their employer(s) unless otherwise stated in the text
      of the article) 2018. All rights reserved. No commercial use is permitted unless 
      otherwise expressly granted.
FAU - Grouthier, Virginie
AU  - Grouthier V
AD  - Department of Endocrinology and Reproductive Medicine, Sorbonne Universites,
      AP-HP, Pitie-Salpetriere Hospital, Centre de Reference des Maladies
      Endocriniennes Rares de la Croissance, Centre de Reference des Pathologies
      Gynecologiques Rares, Paris, France.
FAU - Lebrun-Vignes, Benedicte
AU  - Lebrun-Vignes B
AD  - AP-HP, Pitie-Salpetriere Hospital Department of Pharmacology CIC-1421
      Pharmacovigilance Unit INSERM UMR ICAN 1166 Sorbonne Universite UPMC, Univ Paris 
      06, Institute of CArdiometabolism and Nutrition (ICAN), Paris, France.
FAU - Glazer, Andrew M
AU  - Glazer AM
AD  - Cardio-oncology Program, Departments of Medicine and Pharmacology, Vanderbilt
      University Medical Center, Nashville, Tennessee, USA.
FAU - Touraine, Philippe
AU  - Touraine P
AD  - Department of Endocrinology and Reproductive Medicine, Sorbonne Universites,
      AP-HP, Pitie-Salpetriere Hospital, Centre de Reference des Maladies
      Endocriniennes Rares de la Croissance, Centre de Reference des Pathologies
      Gynecologiques Rares, Paris, France.
FAU - Funck-Brentano, Christian
AU  - Funck-Brentano C
AD  - AP-HP, Pitie-Salpetriere Hospital Department of Pharmacology CIC-1421
      Pharmacovigilance Unit INSERM UMR ICAN 1166 Sorbonne Universite UPMC, Univ Paris 
      06, Institute of CArdiometabolism and Nutrition (ICAN), Paris, France.
FAU - Pariente, Antoine
AU  - Pariente A
AD  - Department of Pharmacology, Team Pharmaco-Epidemiology, CHU de Bordeaux, INSERM, 
      CIC-1401, Bordeaux Population Health Research Center, University of Bordeaux,
      Bordeaux, France.
FAU - Courtillot, Carine
AU  - Courtillot C
AD  - Department of Endocrinology and Reproductive Medicine, Sorbonne Universites,
      AP-HP, Pitie-Salpetriere Hospital, Centre de Reference des Maladies
      Endocriniennes Rares de la Croissance, Centre de Reference des Pathologies
      Gynecologiques Rares, Paris, France.
FAU - Bachelot, Anne
AU  - Bachelot A
AD  - Department of Endocrinology and Reproductive Medicine, Sorbonne Universites,
      AP-HP, Pitie-Salpetriere Hospital, Centre de Reference des Maladies
      Endocriniennes Rares de la Croissance, Centre de Reference des Pathologies
      Gynecologiques Rares, Paris, France.
FAU - Roden, Dan M
AU  - Roden DM
AD  - Cardio-oncology Program, Departments of Medicine and Pharmacology, Vanderbilt
      University Medical Center, Nashville, Tennessee, USA.
FAU - Moslehi, Javid J
AU  - Moslehi JJ
AD  - Cardio-oncology Program, Departments of Medicine and Pharmacology, Vanderbilt
      University Medical Center, Nashville, Tennessee, USA.
FAU - Salem, Joe-Elie
AU  - Salem JE
AUID- ORCID: 0000-0002-0331-3307
AD  - AP-HP, Pitie-Salpetriere Hospital Department of Pharmacology CIC-1421
      Pharmacovigilance Unit INSERM UMR ICAN 1166 Sorbonne Universite UPMC, Univ Paris 
      06, Institute of CArdiometabolism and Nutrition (ICAN), Paris, France.
AD  - Cardio-oncology Program, Departments of Medicine and Pharmacology, Vanderbilt
      University Medical Center, Nashville, Tennessee, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03259711
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180502
PL  - England
TA  - Heart
JT  - Heart (British Cardiac Society)
JID - 9602087
RN  - 0 (Aromatase Inhibitors)
RN  - 0 (Selective Estrogen Receptor Modulators)
RN  - 094ZI81Y45 (Tamoxifen)
SB  - AIM
SB  - IM
MH  - Action Potentials/drug effects
MH  - Adolescent
MH  - Adult
MH  - *Adverse Drug Reaction Reporting Systems
MH  - Aged
MH  - Aged, 80 and over
MH  - Aromatase Inhibitors/*adverse effects
MH  - Cardiotoxicity
MH  - Databases, Factual
MH  - Europe/epidemiology
MH  - Female
MH  - Heart Conduction System/*drug effects/physiopathology
MH  - Heart Rate/*drug effects
MH  - Humans
MH  - Long QT Syndrome/*chemically induced/diagnosis/mortality/physiopathology
MH  - Middle Aged
MH  - Prognosis
MH  - Risk Assessment
MH  - Risk Factors
MH  - Selective Estrogen Receptor Modulators/*adverse effects
MH  - Tamoxifen/*adverse effects
MH  - Torsades de Pointes/*chemically induced/diagnosis/mortality/physiopathology
MH  - Young Adult
OTO - NOTNLM
OT  - *Long QT syndrome
OT  - *aromatase inhibitors
OT  - *selective estrogen receptor modulators
OT  - *sex steroid hormones
OT  - *torsade de pointes
OT  - *ventricular arrhythmias
COIS- Competing interests: JJM (Consultant: Novartis,Pfizer, Bristol Myers Squibb,
      Takeda). The other authors have nothing to disclose.
EDAT- 2018/05/04 06:00
MHDA- 2019/03/15 06:00
CRDT- 2018/05/04 06:00
PHST- 2018/01/02 00:00 [received]
PHST- 2018/03/19 00:00 [revised]
PHST- 2018/04/09 00:00 [accepted]
PHST- 2018/05/04 06:00 [pubmed]
PHST- 2019/03/15 06:00 [medline]
PHST- 2018/05/04 06:00 [entrez]
AID - heartjnl-2017-312934 [pii]
AID - 10.1136/heartjnl-2017-312934 [doi]
PST - ppublish
SO  - Heart. 2018 Nov;104(22):1859-1863. doi: 10.1136/heartjnl-2017-312934. Epub 2018
      May 2.