Tyrosine kinase inhibitors – should we worry about cardiovascular complications?
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Small-molecular tyrosine kinase inhibitors constitute an effective therapeutic option in patients with hematologic malignancies and solid tumours. On the other hand, the significance of cardiovascular adverse events associated with their use is often emphasised. The events include arterial hypertension, heart failure, coronary disease/acute coronary syndromes, and long QT syndrome. The paper discusses the underlying mechanisms behind cardiovascular events associated with the treatment that involves tyrosine kinase inhibitors, and presents preventive and therapeutic options available in clinical practice. Awareness of the potential cardiovascular complications, regular follow-up, early diagnosis and initiation of appropriate treatment, combined with close collaboration with cardiology specialists, may enhance the benefits of long-term TKI therapy.
- 1. Krause DS, Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med 2005; 353(2): 172-187.
- 2. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J 2016; 37: 2768-2801.
- 3. Izzedine H, Ederhy S, Goldwasser F et al. Management of hypertension in angiogenesis inhibitor-treated patients. Ann Oncol 2009; 20: 807-815.
- 4. Zhu X, Stergiopoulos K, Wu S. Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: Systematic review and meta- analysis. Acta Oncologica 2009; 48: 9-17.
- 5. Hamnvik OPR, Choueiri TK, Turchin A et al. Clinical risk factors for the development of hypertension in patients treated with inhibitors of the VEGF signaling pathway. Cancer 2015; 121(2): 311-319.
- 6. 2013 ESH/ESC Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013; 34: 2159-2219.
- 7. Zasady postępowania w nadciśnieniu tętniczym – 2015 rok. Wytyczne Polskiego Towarzystwa Nadciśnienia Tętniczego. Nadciśnienie Tętnicze w Praktyce 2015; 1(1): 1-70.
- 8. Rini BI, Cohen DP, Lu DR et al. Hypertension as a Biomarker of Efficacy in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib. J Natl Cancer Inst 2011; 103: 763-773.
- 9. Ghatalia P, Morgan CJ, Je Y et al. Congestive heart failure with vascular endothelial growth factor receptor tyrosine kinase inhibitors. Crit Rev Oncol Hematol 2015; 94(2): 228-237.
- 10. Hahn VS, Lenihan DJ, Ky B. Cancer therapy-induced cardiotoxicity: basic mechanisms and potential cardioprotective therapies. J Am Heart Assoc 2014; 3(2): e000665. DOI: 10.1161/JAHA.113.000665.
- 11. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Eur Heart J 2016; 37: 2129-2200.
- 12. Hall PS, Harshman LC, Srinivas S et al. The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients. JACC Heart Fail 2013; 1(1): 72-78.
- 13. Herrmann J, Yang EH, Iliescu CA et al. Vascular Toxicities of Cancer Therapies The Old and the New – An Evolving Avenue. Circulation 2016; 133:1272-1289.
- 14. Dahlén T, Edgren G, Lambe M et al. Cardiovascular Events Associated With Use of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Population- Based Cohort Study. Ann Intern Med 2016; 165(3): 161-166.
- 15. Valent P, Hadzijusufovic E, Schernthaner GH et al. Vascular safety issues in CML patients treated with BCR/ABL1 kinase inhibitors. Blood 2015; 125(6): 901-906.
- 16. 2013 ESC guidelines on the management of stable coronary artery disease. The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013; 34: 2949-3003.
- 17. Kloth JSL, Pagani S, Verboom MC et al. Incidence and relevance of QTc-interval prolongation caused by tyrosine kinase inhibitors. Br J Cancer 2015; 112: 1011-1016.
- 18. Lenihan DJ, Kowey PR. Overview and Management of Cardiac Adverse Events Associated With Tyrosine Kinase Inhibitors. The Oncologist 2013; 18: 900-908.
- 19. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Eur Heart J 2015; 36(41): 2793-2867.
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