Cardiovascular safety of rapidly accelerated fibrosarcoma B-type and/or mitogen-activated extracellular signal-regulated kinase inhibitors: A mixed approach combining a meta-analysis and a pharmacovigilance disproportionality analysis.

Details

Serval ID
serval:BIB_7CE8172A0C7F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cardiovascular safety of rapidly accelerated fibrosarcoma B-type and/or mitogen-activated extracellular signal-regulated kinase inhibitors: A mixed approach combining a meta-analysis and a pharmacovigilance disproportionality analysis.
Journal
Archives of cardiovascular diseases
Author(s)
Dolladille C., Font J., Bejan-Angoulvant T., Zaman K., Sassier M., Ezine E., Stefan A., Plane A.F., Legallois D., Milliez P., Parienti J.J., Alexandre J.
ISSN
1875-2128 (Electronic)
ISSN-L
1875-2128
Publication state
Published
Issued date
2020
Peer-reviewed
Oui
Volume
113
Number
6-7
Pages
420-432
Language
english
Notes
Publication types: Journal Article ; Meta-Analysis ; Systematic Review
Publication Status: ppublish
Abstract
The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is not fully characterized.
To evaluate the cardiovascular adverse events risks related to BRAF and/or MEK inhibitors in randomized placebo-controlled clinical trials and in the real-life setting.
We used two approaches. First, we conducted a systematic review and meta-analysis of randomized placebo-controlled clinical trials reporting the incidence of cardiovascular adverse events for BRAF and/or MEK inhibitors in cancer patients. Second, we performed a disproportionality analysis, using age- and sex-adjusted reporting odds ratios (arORs) and their 95% confidence intervals (CIs) from the World Health Organization's pharmacovigilance database (VigiBase®) of anticancer drug-associated reports, to investigate real-life data.
MEK inhibitors increased the risk of ejection fraction decrease (odds ratio [OR] 3.35, 95% CI 1.58-7.07), peripheral oedema (OR 2.87 95% CI 1.93-4.27) and syncope (OR 6.71, 95% CI 3.00-14.99) compared with placebo in randomized placebo-controlled clinical trials. BRAF and MEK inhibitor combination therapy further increased the risk of ejection fraction decrease. In the disproportionality analysis, we found over-reporting of ejection fraction decrease (arOR 8.42, 95% CI 7.03-10.09), peripheral oedema (arOR 1.39, 95% CI 1.17-1.66), syncope (arOR 1.56, 95% CI 1.22-1.99), torsade de pointes/QT prolongation (arOR 6.13, 95% CI 5.04-7.47) and supraventricular arrhythmias (arOR 1.50, 95% CI 1.21-1.85) for BRAF and MEK inhibitors. BRAF and MEK inhibitors were not associated with hypertension in either approach.
In conclusion, MEK inhibitors increase the risk of ejection fraction decrease, peripheral oedema and syncope in randomized placebo-controlled clinical trials. Real-life data confirm these findings, and suggested additional risks of torsade de pointes/QT prolongation and supraventricular arrhythmias with BRAF/MEK inhibitors.
Keywords
Adverse Drug Reaction Reporting Systems, Aged, Antineoplastic Agents/adverse effects, Cardiovascular Diseases/chemically induced, Cardiovascular Diseases/diagnosis, Cardiovascular Diseases/epidemiology, Cardiovascular Diseases/physiopathology, Databases, Factual, Female, Fibrosarcoma/drug therapy, Fibrosarcoma/enzymology, Fibrosarcoma/epidemiology, Fibrosarcoma/genetics, Humans, Male, Middle Aged, Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors, Mitogen-Activated Protein Kinase Kinases/metabolism, Patient Safety, Pharmacovigilance, Protein Kinase Inhibitors/adverse effects, Proto-Oncogene Proteins B-raf/antagonists & inhibitors, Proto-Oncogene Proteins B-raf/genetics, Proto-Oncogene Proteins B-raf/metabolism, Randomized Controlled Trials as Topic, Risk Assessment, Risk Factors, Treatment Outcome, Analyse de disproportionalité, BRAF inhibitors, Cardiovascular adverse events, Disproportionality analysis, Evènements indésirables cardio-vasculaires, Inhibiteurs de BRAF, Inhibiteurs de MEK, MEK inhibitors, Méta-analyse de sécurité, Safety meta-analysis
Pubmed
Web of science
Open Access
Yes
Create date
14/06/2020 19:55
Last modification date
08/12/2020 6:24
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