Cardiovascular Adverse Events Associated With BRAF and MEK Inhibitors: A Systematic Review and Meta-analysis

Cardiovascular adverse events (CVAEs) after treatment with BRAF and MEK inhibitors in patients with melanoma remain incompletely characterized. To determine the association of BRAF and MEK inhibitor treatment with CVAEs in patients with melanoma compared with BRAF inhibitor monotherapy. PubMed, Coch...

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Bibliographic Details
Published in:JAMA network open 2019-08, Vol.2 (8), p.e198890-e198890
Main Authors: Mincu, Raluca I, Mahabadi, Amir A, Michel, Lars, Mrotzek, Simone M, Schadendorf, Dirk, Rassaf, Tienush, Totzeck, Matthias
Format: Article
Language:English
Subjects:
Cardiac arrhythmia
Cardiology
Clinical trials
Ejection fraction
Heart attacks
Hypertension
Melanoma
Meta-analysis
Online Only
Original Investigation
Pulmonary embolisms
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Summary:Cardiovascular adverse events (CVAEs) after treatment with BRAF and MEK inhibitors in patients with melanoma remain incompletely characterized. To determine the association of BRAF and MEK inhibitor treatment with CVAEs in patients with melanoma compared with BRAF inhibitor monotherapy. PubMed, Cochrane, and Web of Science were systematically searched for keywords vemurafenib, dabrafenib, encorafenib, trametinib, binimetinib, and cobinimetinib from database inception through November 30, 2018. Randomized clinical trials reporting on CVAEs in patients with melanoma being treated with BRAF and MEK inhibitors compared with patients with melanoma being treated with BRAF inhibitor monotherapy were selected. Data assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Pooled relative risks (RRs) and 95% CIs were determined using random-effects and fixed-effects analyses. Subgroup analyses were conducted to assess study-level characteristics associated with CVAEs. The selected end points were pulmonary embolism, a decrease in left ventricular ejection fraction, arterial hypertension, myocardial infarction, atrial fibrillation, and QTc interval prolongation. All-grade and high-grade (≥3) CVAEs were recorded. Overall, 5 randomized clinical trials including 2317 patients with melanoma were selected. Treatment with BRAF and MEK inhibitors was associated with an increased risk of pulmonary embolism (RR, 4.36; 95% CI, 1.23-15.44; P = .02), a decrease in left ventricular ejection fraction (RR, 3.72; 95% CI, 1.74-7.94; P 
ISSN:2574-3805
2574-3805
DOI:10.1001/jamanetworkopen.2019.8890