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Cardiovascular Damage Induced by Anti-BCR-ABL TKIs

  • Giuseppina Novo
  • Daniela Di Lisi
  • Manuela Fiuza
  • Fausto J. Pinto
Chapter
Part of the Current Clinical Pathology book series (CCPATH)

Abstract

Anti-BCR-ABL TKIs (tyrosine kinase inhibitors) are drugs that inhibit BCR ABL tyrosine. They are used especially in the treatment of hematological cancer and gastrointestinal stromal tumors (GIST). Anti-BCR-ABL TKIs include first (imatinib), second (nilotinib, dasatinib, bosutinib) and third-generation drugs (ponatinib). Especially second- and third-generation drugs can cause cardiovascular complications such as arterial thrombosis, myocardial ischemia, peripheral arterial diseases, QTc prolongation, and pulmonary hypertension. Nilotinib and ponatinib can cause thrombotic arterial events with various mechanisms. Particularly dasatinib can cause pulmonary hypertension. Compared to conventional chemotherapy, myocardial dysfunction was found in a smaller number of cases. In this chapter, we will illustrate cardiovascular adverse effects induced by anti-BCR-ABL TKIs, the main mechanisms that could explain such effects, and the influence played by cardiovascular risk factors. It is essential for both cardiologists and oncologists to know these issues in order to develop appropriate monitoring and apply preventive strategies to avoid the occurrence of toxicity and the need of any premature interruption of the antineoplastic treatment.

Keywords

Anti-BCR-ABL Nilotinib Ponatinib Imatinib Dasatinib Tyrosine kinase inhibitors Cardiotoxicity Cardioncology 

References

  1. 1.
    Nowell P, Hungerford D. A minute chromosome in human chronic granulocytic leukemia. Land-marks in Medical Genetics: classic papers with commentaries. 2004;132(51):103.Google Scholar
  2. 2.
    Rowley JD. A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Landmarks in Medical Genetics: classic papers with commentaries. 2004;243(51):104.Google Scholar
  3. 3.
    Tocchetti CG, Cadeddu C, Di Lisi D, Femminò S, Madonna R, Mele D, et al. From molecular mechanisms to clinical management of antineoplastic drug-induced cardiovascular toxicity: a translational overview. Antioxid Redox Signal. 2017;  https://doi.org/10.1089/ars.2016.6930.
  4. 4.
    Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012;367:2075–88.CrossRefGoogle Scholar
  5. 5.
    Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, et al. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013;369:1783–96.CrossRefGoogle Scholar
  6. 6.
    Mughal A, Aslam HM, Khan AM, Saleem S, Umah R, Saleem M. Bcr-Abl tyrosine kinase inhibitors- current status. Infect Agent Cancer. 2013;8:23.CrossRefGoogle Scholar
  7. 7.
    Verweij J, Casali PG, Kotasek D, Le Cesne A, Reichard P, Judson IR, et al. Imatinib does not induce cardiac left ventricular failure in gastrointestinal stromal tumours patients: analysis of EORTC-ISG-AGITG study 62005. Eur J Cancer. 2007;43:974–8.CrossRefGoogle Scholar
  8. 8.
    Groarke JD, Cheng S, Moslehi J. Cancer-drug discovery and cardiovascular surveillance. N Engl J Med. 2013;369:1779–81.CrossRefGoogle Scholar
  9. 9.
    Valent P, Hadzijusufovic E, Schernthaner GH, Wolf D, Rea D, Le Coutre P. Vascular safety issues in CML patients treated with BCR/ABL1 kinase inhibitors. Blood. 2015;125:901–6.CrossRefGoogle Scholar
  10. 10.
    Damrongwatanasuk R, Fradley MG. Cardiovascular complications of targeted therapies for chronic myeloid leukemia. Curr Treat Options Cardiovasc Med. 2017;19(4):24.CrossRefGoogle Scholar
  11. 11.
    Chen ZI, Ai DI. Cardiotoxicity associated with targeted cancer therapies. Mol Clin Oncol. 2016;4(5):675–81.CrossRefGoogle Scholar
  12. 12.
    Atallah E, Durand JB, Kantarjian H, Cortes J. Congestive heart failure is a rare event in patients receiving imatinib therapy. Blood. 2007;110:1233–7.CrossRefGoogle Scholar
  13. 13.
    Hatfield A, Owen S, Pilot PR. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med. 2007;13:15–6.CrossRefGoogle Scholar
  14. 14.
    Garcia-Alvarez A, Sitges M, Garcia-Albeniz X, , Sionis A, Loma-Osorio P, Bosch X. Atypical cardiac manifestation of hypereosinophilic syndrome and reversible cardiotoxicity to imatinib. Int J Cardiol 2010;139:e29–e31.CrossRefGoogle Scholar
  15. 15.
    Maharsy W, Aries A, Mansour O, Komati H, Nemer M. Ageing is a risk factor in imatinib mesylate cardiotoxicity. Eur J Heart Fail. 2014;16:367–76.CrossRefGoogle Scholar
  16. 16.
    Garcia-Alvarez A, Garcia-Albeniz X, Esteve J, Rovira M, Bosch X. Cardiotoxicity of tyrosine-kinase-targeting drugs. Cardiovasc Hematol Agents Med Chem. 2010;8:11–21.CrossRefGoogle Scholar
  17. 17.
    Speich R, Ulrich S, Domenighetti G, Huber LC, Fischler M, Treder U, et al. Efficacy and safety of long-term imatinib therapy for pulmonary arterial hypertension. Respiration. 2015;89:515–24.CrossRefGoogle Scholar
  18. 18.
    Farha S, Dweik R, Rahaghi F, Benza R, Hassoun P, Frantz R, et al. Imatinib in pulmonary arterial hypertension: c-kit inhibition. Pulm Circ. 2014;4:452–5.CrossRefGoogle Scholar
  19. 19.
    Salaroli A, Loglisci G, Serrao A, Alimena G, Breccia M. Fasting glucose level reduction induced by imatinib in chronic myeloproliferative disease with TEL-PDGFRβ rearrangement and type 1 diabetes. Ann Hematol. 2012;91:1823–4.CrossRefGoogle Scholar
  20. 20.
    Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–17.CrossRefGoogle Scholar
  21. 21.
    Jang SW, Ihm SH, Choo EH, Kim OR, Chang K, Park CS, et al. Imatinib mesylate attenuates myocardial remodeling through inhibition of platelet- derived growth factor and transforming growth factor activation in a rat model of hypertension. Hypertension. 2014;63:1228–34.CrossRefGoogle Scholar
  22. 22.
    Kerkela R, Grazette L, Yacobi R, Illiescu C, Patten R, Beahm C, et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med. 2006;12:908–16.CrossRefGoogle Scholar
  23. 23.
    Shimazaki C, Ochiai N, Uchida R, Fuchida SI, Okano A, Ashihara E, et al. Intramuscular edema as a complication of treatment with imatinib. Leukemia. 2003;17:804–5.CrossRefGoogle Scholar
  24. 24.
    Su EJ, Fredriksson L, Geyer M, Folestad E, Cale J, Andrae J, et al. Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke. Nat Med. 2008;14:731–73.CrossRefGoogle Scholar
  25. 25.
    Hoeper MM, Barst RJ, Bourge RC, Feldman J, Frost AE, Galie N, et al. Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Circulation. 2013;127:1128–38.CrossRefGoogle Scholar
  26. 26.
    Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoll J, Paquette R, et al. Dasatinib in imatinib resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006;354:2531–54.CrossRefGoogle Scholar
  27. 27.
    Quinta’s-Cardama A, Kantarjian H, O’Brien S, Borthakur G, Bruzzi J, Munden R, et al. Pleural effusion in patients with chronic myelogenous leukemia treated with dasatinib after imatinib failure. J Clin Oncol. 2007;25:3908–14.CrossRefGoogle Scholar
  28. 28.
    Montani D, Bergot E, Günther S, Savale L, Bergeron A, Bourdin A, et al. Pulmonary arterial hyper-tension in patients treated by dasatinib. Circulation. 2012;125:2128–37.CrossRefGoogle Scholar
  29. 29.
    Shah NP, Rousselot P, Schiffer C, Rea D, Cortes JE, Milone J, et al. Dasatinib in imatinib-resistant or intolerant chronic-phase, chronic myeloid leukemia patients: 7-year follow-up of study CA180-034. Am J Hematol. 2016;91:869–74.CrossRefGoogle Scholar
  30. 30.
    Shah NP, Wallis N, Farber HW, Mauro MJ, Wolf RA, Mattei D, et al. Clinical features of pulmonary arterial hypertension in patients receiving dasatinib. Am J Hematol. 2015;90:1060–4.CrossRefGoogle Scholar
  31. 31.
    Hong JH, Lee S, Choi SY, Kim SH, Jang EJ, Bang JH, et al. Reversible pulmonary arterial hypertension associated with dasatinib for chronic myeloid leukemia. Cancer Res Treat. 2015;47:937–42.CrossRefGoogle Scholar
  32. 32.
    Cortes J, Mauro M, Steegmann JL, Saglio G, Malhotra R, Ukropec JA, et al. Cardio-vascular and pulmonary adverse events in patients treated with BCR-ABL inhibitors: data from the FDA Adverse Event Reporting System. Am J Hematol. 2015;90:E66–72.CrossRefGoogle Scholar
  33. 33.
    Balasubramaniam V, Le Cras TD, Ivy DD, Grover TR, Kinsella JP, Abman SH. Role of platelet-derived growth factor in vascular remodeling during pulmonary hypertension in the ovine fetus. Am J Physiol Lung Cell Mol Physiol. 2003;284:826–33.CrossRefGoogle Scholar
  34. 34.
    Perros F, Montani D, Dorfmuller P, Durand-Gasselin I, Tcherakian C, Le Pavec J, et al. Platelet-derived growth factor expression and function in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med. 2008;178:81–8.CrossRefGoogle Scholar
  35. 35.
    Oda Y, Renaux B, Bjorge J, Saifeddine M, Fujita DJ, Hollenberg MD. cSrc is a major cytosolic tyrosine kinase in vascular tissue. Can J Physiol Pharmacol. 1999;77:606–17.CrossRefGoogle Scholar
  36. 36.
    Masiello D, Gorospe G, Yang A. The occurrence and management of fluid retention associated with TKI therapy in CML, with a focus on dasatinib. J Hematol Oncol. 2009;2:46.CrossRefGoogle Scholar
  37. 37.
    Usküdar Teke H, Akay OM, Gören Şahin D, Karagülle M, Gündüz E, Andıç N. Pleural effusion: a rare side effect of nilotinib-a case report. Case Rep Med. 2014;2014:203939.CrossRefGoogle Scholar
  38. 38.
    Kelly K, Swords R, Mahalingam D, Padmanabhan S, Giles FJ. Serosal inflammation (pleural and pericardial effusions) related to tyrosine kinase inhibitors. Target Oncol. 2009;4:99–105.CrossRefGoogle Scholar
  39. 39.
    Paydas S. Dasatinib, large granular lymphocytosis, and pleural effusion: useful or adverse effect? Crit Rev Oncol Hematol. 2014;89:242–7.CrossRefGoogle Scholar
  40. 40.
    Eskazan AE, Eyice D, Kurt EA, Elverdi T, Yalniz FF, Salihoglu A, et al. Chronic myeloid leukemia patients who develop grade I/II pleural effusion under second-line dasatinib have better responses and outcomes than patients without pleural effusion. Leuk Res. 2014;38:781–7.CrossRefGoogle Scholar
  41. 41.
    Guignabert C, Phan C, Seferian A, Huertas A, Tu L, Thuillet R, et al. Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension. J Clin Invest. 2016;126:3207–18.CrossRefGoogle Scholar
  42. 42.
    Green MR, Newton MD, Fancher KM. Off-target effects of BCR-ABL and JAK2 inhibitors. Am J Clin Oncol. 2016;39:76–84.CrossRefGoogle Scholar
  43. 43.
    Chai-Adisaksopha C, Lam W, Hillis C. Major arterial events in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a meta-analysis. Leuk Lymphoma. 2016;57:1300–10.CrossRefGoogle Scholar
  44. 44.
    Aichberger KJ, Herndlhofer S, Schernthaner GH, Schillinger M, Mitterbauer-Hohendanner G, Sillaber C, et al. Progressive peripheral arterial occlusive disease and other vascular events during nilotinib therapy in CML. Am J Hematol. 2011;86:533–9.CrossRefGoogle Scholar
  45. 45.
    Giles FJ, Mauro MJ, Hong F, Ortmann CE, McNeill C, Woodman RC, et al. Rates of peripheral arterial occlusive disease in patients with chronic myeloid leukemia in the chronic phase treated with imatinib, nilotinib, or non-tyrosine kinase therapy: a retrospective cohort analysis. Leukemia. 2013;27:1310–5.CrossRefGoogle Scholar
  46. 46.
    Tajiri K, Aonuma K, Sekine I. Cardiovascular toxic effects of targeted cancer therapy. Jpn J Clin Oncol. 2017;47:779–85.CrossRefGoogle Scholar
  47. 47.
    Rea D, Mirault T, Raffoux E, et al. Identification of patients with chronic myeloid leukemia at high risk of artery occlusive events during treatment with the 2nd generation tyrosine kinase inhibitor nilotinib, using risk stratification for cardiovascular diseases. Blood. 2013;122(21):2726.Google Scholar
  48. 48.
    Jager NG, Stuurman FE, Baars JW, Opdam FL. Cerebrovascular events during nilotinib treatment. Neth J Med. 2014;72:113–4.PubMedGoogle Scholar
  49. 49.
    Valent P, Hadzijusufovic E, Hoermann G, Füreder W, Schernthaner GH, Sperr WR, et al. Risk factors and mechanisms contributing to TKI-induced vascular events in patients with CML. Leuk Res. 2017;59:47–54.CrossRefGoogle Scholar
  50. 50.
    Jeon YW, Lee SE, Choi SY, et al. Peripheral arterial occlusive disease (PAOD) in chronic phase chronic myeloid leukemia patients treated with nilotinib. Blood. 2013;122(21):2726.Google Scholar
  51. 51.
    Kantarjian HM, Hochhaus A, Saglio G, De Souza C, Flinn IW, Stenke L, et al. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome- positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol. 2011;12:841–51.CrossRefGoogle Scholar
  52. 52.
    Labussiere-Wallet H, Guillermin Y, Etienne M, et al. Analysis of clinical arterial and metabolic parameters in chronic phase cml patients on nilotinib in a single center cohort. Blood. 2012;120(21):2726.Google Scholar
  53. 53.
    Breccia M, Muscaritoli M, Gentilini F, Latagliata R, Carmosino I, Rossi Fanelli F, et al. Impaired fasting glucose level as metabolic side effect of nilotinib in non-diabetic chronic myeloid leukemia patients resistant to imatinib. Leuk Res. 2007;31:1770–2.CrossRefGoogle Scholar
  54. 54.
    Hiwase DK, Yeung DT, Carne L, Ross D, Grigg A, Hughes TP. Hypercholesterolemia in imatinib intolerant/resistant CML-CP patients treated with nilotinib: a retrospective analysis. Blood 2013;122(21):2726.Google Scholar
  55. 55.
    Hadzijusufovic E, Herndlhofer S, Aichberger KJ, et al. Nilotinib exerts direct effects on vascular endothelial cells and may act as a co-trigger of atherosclerosis in patients with Ph+ CML. Blood. 2013;118(21):2726.Google Scholar
  56. 56.
    Quintas-Cardama A, Kantarjian H, Cortes J. Nilotinib-associated vascular events. Clin Lymphoma Myeloma Leuk. 2012;12:337–40.CrossRefGoogle Scholar
  57. 57.
    Franco C, Britto K, Wong E, Hou G, , Zhu SN, Chen M, et al. Discoidin domain receptor 1 on bone marrow-derived cells promotes macrophage accumulation during atherogenesis. Circ Res 2009;105:1141–1148.CrossRefGoogle Scholar
  58. 58.
    Sillaber C, Baghestanian M, Bevec D, Willheim M, Agis H, Kapiotis S, et al. The mast cell as site of tissue-type plasminogen activator expression and fibrinolysis. J Immunol. 1999;162:1032–41.PubMedGoogle Scholar
  59. 59.
    Valent P, Baghestanian M, Bankl HC, Sillaber C, Sperr WR, Wojta J, et al. New aspects in thrombosis research: possible role of mast cells as profibrinolytic and antithrombotic cells. Thromb Haemost. 2002;87:786–90.CrossRefGoogle Scholar
  60. 60.
    Larson RA, Yin OQ, Hochhaus A, Saglio G, Clark RE, Nakamae H, et al. Population pharmacokinetic and exposure- response analysis of nilotinib in patients with newly diagnosed Ph± chronic myeloid leukemia in chronic phase. Eur J Clin Pharmacol. 2012;68:723–33.CrossRefGoogle Scholar
  61. 61.
    Ito Y, Miyamoto T, Chong Y, Maki T, Akashi K, Kamimura T. Nilotinib exacerbates diabetes mellitus by decreasing secretion of endogenous insulin. Int J Hematol. 2013;9:135–8.CrossRefGoogle Scholar
  62. 62.
    Kantarjian H, Giles F, Wunderle L, Bhalla K, O’Brien S, Wassmann B, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromo-some-positive ALL. N Engl J Med. 2006;354:2542–51.CrossRefGoogle Scholar
  63. 63.
    Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M, et al. 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;37:2768–801.CrossRefGoogle Scholar
  64. 64.
    Moslehi JJ, Deininger M. Tyrosine kinase inhibitor-associated cardiovascular toxicity in chronic myeloid leukemia. J Clin Oncol. 2015;33:4210–8.CrossRefGoogle Scholar
  65. 65.
    Cortes J, Mauro M, Steegmann JL, Saglio G, Malhotra R, Ukropec JA, et al. Cardiovascular and pulmonary adverse events in patients treated with BCR-ABL inhibitors: data from the FDA Adverse Event Reporting System. Am J Hematol. 2015;90:E66–72.CrossRefGoogle Scholar
  66. 66.
    Hasinoff BB, Patel D, Wu X. The myocyte-damaging effects of the BCR-ABL1-targeted tyrosine kinase inhibitors increase with potency and decrease with specificity. Cardiovasc Toxicol. 2017;17(3):297–306.CrossRefGoogle Scholar
  67. 67.
    Okabe S, Tauchi T, Tanaka Y, Ohyashiki K. Efficacy of ponatinib against ABL tyrosine kinase inhibitor-resistant leukemia cells. Biochem Biophys Res Commun. 2013;435:506–11.CrossRefGoogle Scholar
  68. 68.
    Loren CP, Aslan JE, Rigg RA, Nowak MS, Healy LD, Gruber A, et al. The BCR-ABL inhibitor ponatinib inhibits platelet immuno-receptor tyrosine-based activation motif (ITAM) signaling, platelet activation and aggregate formation under shear. Thromb Res. 2015;135:155–60.CrossRefGoogle Scholar
  69. 69.
    Fogarasi Szabo N, Diezi L, Delenclos L, Renard D, Chtioui H, Rothuizen LE, et al. [Pharmacovigilance update]. Rev Med Suisse. 2015;11:456–7. [Article in French].Google Scholar
  70. 70.
    Lipton JH, Chuah C, Guerci-Bresler A, Rosti G, Simpson D, Assouline S, et al. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17:612–21.CrossRefGoogle Scholar
  71. 71.
    Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, et al. A phase 2 trial of ponatinib in Philadelphia chromo-some-positive leukemias. N Engl J Med. 2013;369:1783–96.CrossRefGoogle Scholar
  72. 72.
    Weatherald J, Chaumais MC, Montani D. Pulmonary arterial hypertension induced by tyrosine kinase inhibitors. Curr Opin Pulm Med. 2017;23(5):392–7.CrossRefGoogle Scholar
  73. 73.
    Nazer B, Humphreys BD, Moslehi J. Effects of novel angiogenesis inhibitors for the treatment of cancer on the cardiovascular system: focus on hypertension. Circulation. 2011;124:1687–91.CrossRefGoogle Scholar
  74. 74.
    Talbert DR, Doherty KR, Trusk PB, Moran DM, Shell SA, Bacus S. A multi-parameter in vitro screen in human stem cell-derived cardiomyocytes identifies ponatinib-induced structural and functional cardiac toxicity. Toxicol Sci. 2015;143:147–55.CrossRefGoogle Scholar
  75. 75.
    Brümmendorf TH, Cortes JE, Khoury HJ, Kantarjian HM, Kim DW, Schafhausen P, et al. Factors influencing long-term efficacy and tolerability of bosutinib in chronic phase chronic myeloid leukaemia resistant or intolerant to imatinib. Br J Haematol. 2016;172:97–110.CrossRefGoogle Scholar
  76. 76.
    Cortes JE, Jean Khoury H, Kantarjian H, Brümmendorf TH, Mauro MJ, Matczak E, et al. Long-term evaluation of cardiac and vascular toxicity in patients with Philadelphia chromosome-positive leukemias treated with bosutinib. Am J Hematol. 2016;91:606–16.CrossRefGoogle Scholar
  77. 77.
    Cortes JE, Kim DW, Kantarjian HM, Brümmendorf TH, Dyagil I, Griskevicius L, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J Clin Oncol. 2012;30:3486–92.CrossRefGoogle Scholar
  78. 78.
    Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): Developed with the special contribution of the European Association for Cardiovascular Prevention and Rehabilitation (EACPR). Eur J Prev Cardiol. 2016;23(11):NP1–NP96.CrossRefGoogle Scholar
  79. 79.
    Breccia M, Arboscello E, Bellodi A, Colafigli G, Molica M, Bergamaschi M, et al. Proposal for a tailored stratification at baseline and monitoring of cardiovascular effects during follow-up in chronic phase chronic myeloid leukemia patients treated with nilotinib frontline. Crit Rev Oncol Hematol. 2016;107:190–8.CrossRefGoogle Scholar
  80. 80.
    Leng GC, Fowkes FG. The Edinburgh Claudication Questionnaire: an improved version of the WHO/Rose Questionnaire for use in epidemiological surveys. J Clin Epidemiol. 1992;45:1101–9.CrossRefGoogle Scholar
  81. 81.
    Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 2010;55:1318–27.CrossRefGoogle Scholar
  82. 82.
    Breccia M, Pregno P, Spallarossa P, Arboscello E, , Ciceri F, Giorgi M, et al. Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: an expert opinion. Ann Hematol 2017;96:549–558.CrossRefGoogle Scholar
  83. 83.
    Loren CP, Aslan JE, Rigg RA, Nowak MS, Healy LD, Gruber A, et al. The BCR-ABL inhibitor ponatinib inhibits platelet immunoreceptor tyrosine-based activation motif (ITAM) signaling, platelet activation and aggregate formation under shear. Thromb Res. 2015;135:155–60.CrossRefGoogle Scholar
  84. 84.
    Bocchia M, Galimberti S, Aprile L, Sicuranza A, Gozzini A, Santilli F, et al. Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in in-creased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients. Oncotarget. 2016;7:72311–721.CrossRefGoogle Scholar
  85. 85.
    Alhawiti N, Burbury KL, Kwa FA, O’Malley CJ, Shuttleworth P, et al. The tyrosine kinase inhibitor, nilotinib potentiates a prothrombotic state. Thromb Res. 2016;145:54–64.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Giuseppina Novo
    • 1
  • Daniela Di Lisi
    • 1
  • Manuela Fiuza
    • 2
  • Fausto J. Pinto
    • 2
  1. 1.Division of Cardiology, Biomedical Department of Internal Medicine and Specialities (DIBIMIS), University of PalermoPalermoItaly
  2. 2.Department of CardiologyUniversity Hospital Santa Maria, CHLN University of LisbonLisbonPortugal

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