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

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BRAF and MEK inhibitors increase cardiovascular risks like pulmonary embolism, reduced ejection fraction, and hypertension in melanoma patients compared to BRAF monotherapy. These findings aid in balancing melanoma treatment benefits against cardiovascular risks.

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Area of Science:

  • Oncology
  • Cardiology
  • Pharmacology

Background:

  • Cardiovascular adverse events (CVAEs) following BRAF and MEK inhibitor therapy for melanoma are not fully understood.
  • Optimizing melanoma treatment requires a clear understanding of associated cardiovascular risks.

Purpose of the Study:

  • To evaluate the association between combined BRAF and MEK inhibitor treatment and CVAEs in melanoma patients.
  • To compare CVAEs in patients receiving BRAF and MEK inhibitors versus BRAF inhibitor monotherapy.

Main Methods:

  • Systematic literature search of PubMed, Cochrane, and Web of Science for relevant randomized clinical trials up to November 30, 2018.
  • Meta-analysis using PRISMA guidelines, calculating pooled relative risks (RRs) and confidence intervals (CIs).
  • Analysis included all-grade and high-grade CVAEs, with subgroup analyses for patient characteristics.

Main Results:

  • Combined BRAF and MEK inhibitors increased risks of pulmonary embolism (RR, 4.36), decreased left ventricular ejection fraction (RR, 3.72), and arterial hypertension (RR, 1.49) versus BRAF monotherapy.
  • Risks for myocardial infarction, atrial fibrillation, and QTc prolongation were similar between treatment groups.
  • Higher risk of decreased ejection fraction was seen in younger patients (<55 years), and higher pulmonary embolism risk in longer follow-up (>15 months).

Conclusions:

  • BRAF and MEK inhibitor combination therapy is linked to increased CVAEs compared to BRAF monotherapy.
  • Findings support careful consideration of cardiovascular risks alongside melanoma treatment efficacy.
  • This research aids clinicians in balancing treatment benefits with potential cardiovascular morbidity and mortality.