Congestive heart failure risk in cancer patients treated with vascular endothelial growth factor tyrosine kinase inhibitors: a systematic review and meta‐analysis of 36 clinical trials

Abstract

AIMSCongestive heart failure (CHF) associated with vascular endothelial growth factor tyrosine-kinase inhibitors (VEGFR-TKIs) has emerged as a relevant problem in clinical and scientific communities. We performed an up-to-date, comprehensive meta-analysis to determine the overall incidence and risk of CHF in cancer patients receiving VEGFR-TKIs. METHODSThe databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to August 31 2013 were searched for relevant articles. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies. RESULTSA total of 10 553 patients from 36 clinical trials were included. The overall incidence of all grade and high grade CHF associated with VEGFR-TKIs was 3.2% (95% CI 1.8%, 5.8%) and 1.4% (95% CI 0.9%, 2.3%), respectively. The use of VEGFR-TKIs significantly increased the risk of developing all grade (OR 2.37, 95% CI 1.76, 3.20, P < 0.001) and high grade (OR 3.51, 95% CI 1.74, 7.05, P < 0.001) CHF. In subgroup analyses, the risk of CHF did not significantly vary with tumour types (P = 0.071 for all grade; P = 0.72 for high grade) and VEGFR-TKIs (P = 0.55 for all grade; P = 0.99 for high grade). Meta-regression indicated that CHF might possibly occur early in the treatment of VEGFR-TKIs. No evidence of publication bias was observed. CONCLUSIONThe use of VEGFR-TKIs is associated with a significantly increased risk of developing congestive heart failure in cancer patients. Clinicians should be aware of this risk and provide close monitoring in patients receiving these therapies.

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines

“…Kardiotoksyczność stwierdzono też w przypadku TKI -sunitinibu, pazopanibu i axitinibu. Leki te powodują dysfunkcję serca u 3-15% pacjentów oraz objawową HF u 1-10% osób [61][62][63][64]. Stosowanie innych inhibitorów VEGF, takich jak sorafenib i wandetanib, również prowadzi do dysfunkcji serca, ale nie ma prospektywnych danych z dużych prób klinicznych.…”

Bevacizumab Increases the Risk of Severe Congestive Heart Failure in Cancer Patients: An Up-to-Date Meta-Analysis with a Focus on Different Subgroups

“…Sunitinib, a small-molecule receptor tyrosine kinase Fig. 3 Relative risk of a all-and b high-grade congestive heart failure associated with bevacizumab versus control inhibitor targeting the VEGF receptor and several other kinases, is associated with an increased risk of CHF in cancer patients [32,33], and the risk of CHF with bevacizumab in breast cancer has also been investigated in a previous meta-analysis conducted by Choueiri et al [14]. However, our meta-analysis differs in several aspects from prior study: we analyze the risk of CHF in a broader spectrum of tumors by using data from all published studies and we were able to include more randomized controlled studies than that previous meta-analysis.…”

The Future Role of Cardio-oncologists

“…10,11 The regimen of the diagnostic tools for the detection of cardiotoxicity consists of ECG (resting tachycardia, ST-T changes, conduction disturbances and QT interval prolongation); echocardiography (2D or 3D LVEF assessment, global longitudinal strain, pericardial effusion, etc. ); nuclear cardiac imaging (LVF assessment using multigated radionuclide angiography); cardiac MRI (LVF and structural changes of the myocardium); and biomarker assessment (challenging data were published on troponins and natriuretic peptides, which seems to be helpful to identify the patients at higher risk or those with early manifestation of cardiotoxicity).…”