Key result
Tyrosine kinase inhibitors significantly increased the risk of cardiac ischaemia (RR 1.69; 95% CI 1.12-2.57; p=0.01) and other severe cardiovascular adverse events in cancer patients.
Why the study?
Do tyrosine kinase inhibitors with anti-VEGF activity increase the risk of cardiovascular adverse events in cancer patients?
Meta-Analysis (n=29,252)
Do tyrosine kinase inhibitors with anti-VEGF activity increase the risk of cardiovascular adverse events in cancer patients?
Relative Risk: 1.69 (95% CI 1.12–2.57)
p-value: p=0.01
Tyrosine kinase inhibitors with anti-VEGF activity significantly increase the risk of severe cardiovascular and thrombotic adverse events in cancer patients, highlighting the need for specific cardiovascular monitoring and treatment strategies.
TKIs linked to higher severe CV and thrombotic events; supports surveillance but leaves optimal strategies open.
Background Targeted therapy with tyrosine kinase inhibitors with anti-vascular endothelial growth factor activity improves survival of cancer patients. Cardiovascular complications are critical and it is unknown whether these require specific treatment strategies. We aimed to clarify the associated risk of cardiovascular adverse events in patients treated with tyrosine kinase inhibitors. Design The design of this study was a meta-analysis of randomised controlled trials. Methods We searched PubMed, Cochrane, EMBASE and Web of Science databases for randomised controlled trials published until January 2017 that assessed patients with different types of cancer treated with or without tyrosine kinase inhibitors in addition to standard chemotherapy. Results A total of 29,252 patients from 71 randomised controlled trials were included. Tyrosine kinase inhibitor treatment was associated with a higher cardiac ischaemia relative risk (relative risk = 1.69; 95% confidence interval: 1.12-2.57; p = 0.01), with the highest risks observed for sorafenib and patients with renal cancer. Risk of thrombocytopaenia (relative risk = 2.2; 95% confidence interval: 1.73-2.79; p < 0.001) was highest for regorafenib and patients with breast cancer. Left ventricular systolic dysfunction was increased after tyrosine kinase inhibitor therapy (relative risk = 2.53; 95% confidence interval:1.79 - 3.57; p < 0.001), with the highest risks reported for sunitinib and hepatocellular cancer. QT corrected interval prolongation (relative risk = 6.25; 95% confidence interval: 3.44-11.38; p < 0.001) and arterial hypertension (relative risk = 3.78; 95% confidence interval: 3.15-4.54; p < 0.001) were reported. The relative risks of arterial adverse events, cerebral ischaemia, venous adverse events and pulmonary embolism were similar across groups. Conclusion Tyrosine kinase inhibitors increase the risk of severe cardiovascular and particularly thrombotic adverse events. Specific treatment regimens when prescribing tyrosine kinase inhibitor therapies appear desirable.
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Totzeck et al. (2018) conducted a meta-analysis in Cancer (n=29,252). Tyrosine kinase inhibitors vs. Standard chemotherapy without tyrosine kinase inhibitors was evaluated on Cardiac ischaemia (RR 1.69, 95% CI 1.12-2.57, p=0.01). Tyrosine kinase inhibitors significantly increased the risk of cardiac ischaemia (RR 1.69; 95% CI 1.12-2.57; p=0.01) and other severe cardiovascular adverse events in cancer patients.
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