Titre
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.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Dolladille, C.
Auteure/Auteur
Font, J.
Auteure/Auteur
Bejan-Angoulvant, T.
Auteure/Auteur
Zaman, K.
Auteure/Auteur
Sassier, M.
Auteure/Auteur
Ezine, E.
Auteure/Auteur
Stefan, A.
Auteure/Auteur
Plane, A.F.
Auteure/Auteur
Legallois, D.
Auteure/Auteur
Milliez, P.
Auteure/Auteur
Parienti, J.J.
Auteure/Auteur
Alexandre, J.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1875-2128
Statut éditorial
Publié
Date de publication
2020
Volume
113
Numéro
6-7
Première page
420
Dernière page/numéro d’article
432
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Meta-Analysis ; Systematic Review
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
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.
Sujets
PID Serval
serval:BIB_7CE8172A0C7F
PMID
Open Access
Oui
Date de création
2020-06-14T18:55:43.201Z
Date de création dans IRIS
2025-05-21T00:35:33Z