Рецепт. 2018; : 572-589
Клинико-фармакологическая характеристика антикоагулянтов
Аннотация
Артериальные и венозные тромбозы остаются ведущими причинами заболеваемости и смертности. Тромбоз артерий – основная причина инфаркта миокарда, ишемического инсульта и критической ишемии нижних конечностей. Тромбоз глубоких вен приводит к развитию тромбоэмболии легочной артерии. Венозные тромбы состоят преимущественно из тромбина и эритроцитов и содержат относительно небольшое количество тромбоцитов. Соответственно, методом выбора в их лечении и профилактике являются антикоагулянты. Антикоагулянты – это лекарственные средства, препятствующие тромбообразованию за счет воздействия на плазменные факторы свертывания крови (нефракционированный и низкомолекулярные гепарины, варфарин и другие антагонисты витамина К, витамин-К-независимые антикоагулянты). Цели антикоагулянтной терапии включают профилактику распространения тромба в острую фазу и предупреждение ранних и поздних рецидивов венозного тромбоза.
В статье представлена клинико-фармакологическая характеристика антикоагулянтов для парентерального и перорального применения. Особое внимание уделено безопасности применения и предупреждению нежелательных эффектов антикоагулянтов в клинической практике.
Список литературы
1. Piccini J.P., Patel M.R., Mahaff ey K.W. et al. (2008) Rivaroxaban, an oral direct factor Xa inhibitor. Expert Opin Investig Drugs, vol. 17, pp. 925–37.
2. Instruktsiya po meditsinskomu primeneniyu lekarstvennogo sredstva Geparin [Summary of product characteristics of medicine Heparine]. Available at: http://www.rceth.by/NDfiles/instr/4316_2000_05_10_15_s.pdf (accessed 25 February 2018)
3. Instruktsiya (informatsiya dlya spetsialistov) po meditsinskomu primeneniyu lekarstvennogo sredstva Varfarin [Summary of product characteristics (for specialists) of medicine Warfarin]. Available at: http://www.rceth.by/NDfiles/instr/16_12_1940_s.pdf (accessed 25 February 2018)
4. Vahanian A., Alfi eri O., Andreotti F., et al. (2012) Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC), European Association for CardioThoracic Surgery (EACTS), Guidelines on the management of valvular heart disease. Eur Heart J, vol. 33, рр. 2451–2496.
5. Camm A.J., Lip G.Y., De Caterina R., Savelieva I. et al. (2012) ESC Committee for Practice Guidelines (CPG). 2012 focused update of the ESC Guidelines for the management of atrial fi brillation: an update of the 2010 ESC Guidelines for the management of atrial fi brillation. Developed with the special contribution of the European Heart Rhythm Association. European Heart Journal, vol. 33, pp. 2719–2747.
6. January C.T., Wann L.S., Alpert J.S., et al. (2014) AHA/ACC/HRS guideline for the management of patients with atrial fi brillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation, vol. 130 (23), pp. 2071–104.
7. Steinberg B.A., Holmes D.N., Ezekowitz M.D. et al. (2013) Rate versus rhythm control for management of atrial fi brillation in clinical practice: results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry. Am Heart J., vol. 165 (4), pp. 622–9.
8. Dezee K., Shimeall W., Douglas K. et al. (2006) Treatment of excessive anticoagulation with phytonadione (vitamin K): a meta-analysis. Arch. Intern. Med., vol. 166, pp. 391–7.
9. Dentali F., Ageno W., Crowther M. (2006) Treatment of coumarin-associated coagulopathy: a systematic review and proposed treatment algorithms. J. Thromb. Haemost., vol. 4, pp. 1853–63.
10. Barillari G., Pasca S., Barillar A. (2012) Emergency reversal of anticoagulation: from theory to real use of prothrombin complex concentrates. A retrospective Italian experience. Blood Transfus., vol. 10, pp. 87–94.
11. Aguilar M., Hart R. et al. (2007) Treatment of Warfarin-Associated Intracerebral Hemorrhage: Literature review and expert Opinion. Mayo Clin. Proc., vol. 82, pp. 182–92.
12. Colomina M., Diez Lobo A., Garutti I. et al. (2012) Perioperative use of prothrombin complex concentrates. Minerva Anestesiol., vol. 78, pp. 358–68.
13. Bruce D., Nokes T. (2008) Prothrombin complex concentrate in severe bleeding: experience in a large tertiary hospital. Crit. Care, vol. 12, pp. 1–9.
14. Mazur-Bialy A.I., Zdebska K., Wypasek E., Undas A. (2013) Repeated bleeding complications during therapy with vitamin K antagonists in a patient with the VKORC1*2A and the CYP2C9*3/*3 alleles: genetic testing to support switching to new oral anticoagulants. Thromb Res., vol. 131 (3), pp. 279–80.
15. Xarelto®. Available at: https://www.rlsnet.ru/tn_index_id_43277.htm (accessed 25 February 2018)
16. Instruktsiya po meditsinskomu primeneniyu preparata Pradaksa [Summary of product characteristics of medicine Pradaxa]. Available at: http://www.rceth.by/NDfiles/instr/8992_09_10_14_15_16_17_i.pdf (accessed 25 February 2018)
17. Budnitz D.S., Lovegrove M.C., Shehab N., Richards C.L. (2011) Emergency hospitalizations for adverse drug events in older Americans. N Eng J Med., vol. 365, pp. 200–2012.
18. Ruff C.T., Giugliano R.P., Braunwald E. et al. (2014) Comparison of the effi cacy and safety of new oral anticoagulants with warfarin in patients with atrial fi brillation: a meta-analysis of randomised trials. Lance, vol. 383 (9921), pp. 955–962.
19. Van der Hulle T., Kooiman J., Den Exter P.L. et al. (2014) Eff ectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost., vol. 12 (3), pp. 320–328.
20. Kaatz S., Kouides P.A., Garcia D.A. et al. (2012) Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol., vol. 87, pp. 141–145.
21. Miesbach W., Seifried E. (2012) New direct oral anticoagulants-current therapeutic options and treatment recommendations for bleeding complications. Thromb Haemost., vol. 108, pp. 625–632.
22. Levy J.H., Ageno W., Chan N.C., Crowther M. (2016) When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH. J Thromb. Haemost., vol. 14, pp. 623–627.
23. Glund S., Stangier J., Schmohl M. et al. (2015) Safety, tolerability, and effi cacy of idarucizumab for the reversal of the anticoagulant eff ect of dabigatran in healthy male volunteers: a randomized, placebo-controlled, double-blind phase 1 trial. Lancet, vol. 386, pp. 680–690.
24. Schiele F., van Ryn J., Canada K. et al. (2014) A specifi c antidote for dabigatran: functional and structural characterization. Blood, vol. 121 (18), pp. 3554–3562.
25. Becker R.C. (2016) The biochemistry, enzymology and pharmacology of non-vitamin K anticoagulant drug reversal agents and antidotes. J Thromb Thrombolysis, vol. 41, pp. 273–278.
26. Frontera J.A., Lewin III J.J., Rabinstein A.A. et al. (2016) Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage. Neurocrit Care, vol. 24 (1), pp. 6–46.
27. Kakkar Ajay K., Mueller Iris (2013) Risk Profi les and Antithrombotic Treatment of Patients Newly Diagnosed with Atrial Fibrillation at Risk of Stroke: Perspectives from the International, Observational, Prospective GARFIELD Registry. PLOS ONE, vol. 8, Is. 5, p. e63479.
28. Marinigh R., Lip G.Y.H., Fiotti N. (2010) Age as a risk factor for stroke in atrial fi brillation patients: Implications for thromboprophylaxis. J Am Coll Cardiol, vol. 56, pp. 827–837.
29. Zalesak M., Siu K., Francis K., et al. (2013) Higher persistence in newly diagnosed nonvalvular atrial fi brillation patients treated with dabigatran versus warfarin. Circ Cardiovasc Qual Outcomes, vol. 6, pp. 567–74.
30. Kirchhof P., Benussi S., Kotecha D., et al. 2016 ESC Guidelines for the management of atrial fi brillation developed in collaboration with EACTS. European Heart Journal. Available at: http://eurheartj.oxfordjournals.org/content/early/2016/08/26/eurheartj.ehw210 (accessed 25 February 2018)
31. Olesen J.B., Lip G.Y., Hansen M.L., et al. (2011) Validation of risk stratifi cation schemes for predicting stroke and thromboembolism in patients with atrial fi brillation: nationwide cohort study. BMJ, vol. 342, pp. d124.
32. Van de Werf F, Bax J, Betriu A et al., for the ESC Committee for Practice Guidelines (2010) Guidelines for the management of atrial fi brillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J., vol. 31, pp. 2369–429.
33. Gadsbell K. (2017) Increased use of oral anticoagulants in patients with atrial fi brillation: temporal trends from 2005 to 2015 in Denmark. EHJ, vol. 38, pp. 899–906.
34. Xiong Q., Lau Y.C., Senoo K. et al. (2015) Non-vitamin K antagonist oral anticoagulants (NOACs) in patients with concomitant atrial fi brillation and heart failure: a systemic review and meta-analysis of randomized trials. Eur J Heart Fail., vol. 17 (11), pp. 1192–200.
35. Connolly S., Parekh A., Reilly P .A., et al. (2009) Rationale and design of RE-LY: randomized evaluation of longterm anticoagulant therapy, warfarin, compared with dabigatran. Am Heart J ., vol. 157 (5), pp. 805–10.
36. ROCKET AF Study Investigators (2010). Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationa le and design of the ROCKET AF study. Am Heart J., vol. 159 (3), pp. 340–347.
37. (2011) Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fi brillation trial. Available at: http://www.anticoagulant-trials.eu/studies-a-z/detail/study/aristotle.html (accessed 2 5 February 2018)
38. Larsen T.B. et al. (2014) Bleeding events among new starters and switchers to dabigatran compared with warfarin in atrial fi brillation. Am J Med., vol. 127 (7), pp. 650–656.
39. Reichman D.J., Wernecke M.E. (2016) Stroke, bleeding, and mortality risks in elderly medicare benefi ciaries treated with dabigatran or rivaroxaban for nonvalvular atrial fi brillation JAMA, vol. 315, pp. 2117–2118.
40. Diener C. (2017) Choosing a particular oral anticoagulant and dose for stroke prevent in individual patients with nonvalvular atrial fi brillation: part 2. EHJ, vol. 38, pp. 860–868.
41. Rekomendatsii ESC po diagnostike i vedeniyu patsientov s ostroi emboliei sistemi legochnoi arterii 2014 [ESC recommendations on d iagnostics and maintaining of patients with acute pulmonary embolism 2014]. Available at: http://scardio.ru/content/Guidelines/Recom%20embolia%208_rkj_1.pdf (accessed 25 February 2018).
42. Voigtlaender M., Langer F. (2017) Direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism. What do we know so f ar? Hamostaseologie, vol. 37 (4), pp. 241–255.
43. Habib G., Lancellotti P., Antunes M.J. et al. (2015) ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Assoc iation for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J., vol. 36 (44), pp. 3075–128.
44. Zamorano J.L., Lancellotti P., Rodrigu ez Muñoz D. 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 fo r cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J., vol. 37 (36), pp. 2768–2801.
Recipe. 2018; : 572-589
The clinical and pharmacological characteristics of anticoagulants
Abstract
Arterial and venous thromboses remain the leading causes of morbidity and mortality. Thrombosis of the arteries is the main cause of myocardial infarction, ischemic stroke and critical lower limb ischemia. Deep vein thrombosis leads to the development of pulmonary embolism. Venous thrombi consist mainly of thrombin and erythrocytes and contain a relatively small number of platelets. Accordingly, anticoagulants are the method of choice in their treatment and prevention. Anticoagulants are drugs that prevent thrombus formation due to exposure to plasma clotting factors (unfractionated and low molecular weight heparins, warfarin and other antagonists of vitamin K, vitamin-K-independent anticoagulants). The objectives of anticoagulant therapy include the prevention of thrombus spread to the acute phase and the prevention of early and late relapses of venous thrombosis.
The article presents the clinical and pharmacological characteristics of anticoagulants for parenteral and oral administration. Particular attention is paid to the safety of use and prevention of undesirable eff ects of anticoagulants in clinical practice.
References
1. Piccini J.P., Patel M.R., Mahaff ey K.W. et al. (2008) Rivaroxaban, an oral direct factor Xa inhibitor. Expert Opin Investig Drugs, vol. 17, pp. 925–37.
2. Instruktsiya po meditsinskomu primeneniyu lekarstvennogo sredstva Geparin [Summary of product characteristics of medicine Heparine]. Available at: http://www.rceth.by/NDfiles/instr/4316_2000_05_10_15_s.pdf (accessed 25 February 2018)
3. Instruktsiya (informatsiya dlya spetsialistov) po meditsinskomu primeneniyu lekarstvennogo sredstva Varfarin [Summary of product characteristics (for specialists) of medicine Warfarin]. Available at: http://www.rceth.by/NDfiles/instr/16_12_1940_s.pdf (accessed 25 February 2018)
4. Vahanian A., Alfi eri O., Andreotti F., et al. (2012) Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC), European Association for CardioThoracic Surgery (EACTS), Guidelines on the management of valvular heart disease. Eur Heart J, vol. 33, rr. 2451–2496.
5. Camm A.J., Lip G.Y., De Caterina R., Savelieva I. et al. (2012) ESC Committee for Practice Guidelines (CPG). 2012 focused update of the ESC Guidelines for the management of atrial fi brillation: an update of the 2010 ESC Guidelines for the management of atrial fi brillation. Developed with the special contribution of the European Heart Rhythm Association. European Heart Journal, vol. 33, pp. 2719–2747.
6. January C.T., Wann L.S., Alpert J.S., et al. (2014) AHA/ACC/HRS guideline for the management of patients with atrial fi brillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation, vol. 130 (23), pp. 2071–104.
7. Steinberg B.A., Holmes D.N., Ezekowitz M.D. et al. (2013) Rate versus rhythm control for management of atrial fi brillation in clinical practice: results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry. Am Heart J., vol. 165 (4), pp. 622–9.
8. Dezee K., Shimeall W., Douglas K. et al. (2006) Treatment of excessive anticoagulation with phytonadione (vitamin K): a meta-analysis. Arch. Intern. Med., vol. 166, pp. 391–7.
9. Dentali F., Ageno W., Crowther M. (2006) Treatment of coumarin-associated coagulopathy: a systematic review and proposed treatment algorithms. J. Thromb. Haemost., vol. 4, pp. 1853–63.
10. Barillari G., Pasca S., Barillar A. (2012) Emergency reversal of anticoagulation: from theory to real use of prothrombin complex concentrates. A retrospective Italian experience. Blood Transfus., vol. 10, pp. 87–94.
11. Aguilar M., Hart R. et al. (2007) Treatment of Warfarin-Associated Intracerebral Hemorrhage: Literature review and expert Opinion. Mayo Clin. Proc., vol. 82, pp. 182–92.
12. Colomina M., Diez Lobo A., Garutti I. et al. (2012) Perioperative use of prothrombin complex concentrates. Minerva Anestesiol., vol. 78, pp. 358–68.
13. Bruce D., Nokes T. (2008) Prothrombin complex concentrate in severe bleeding: experience in a large tertiary hospital. Crit. Care, vol. 12, pp. 1–9.
14. Mazur-Bialy A.I., Zdebska K., Wypasek E., Undas A. (2013) Repeated bleeding complications during therapy with vitamin K antagonists in a patient with the VKORC1*2A and the CYP2C9*3/*3 alleles: genetic testing to support switching to new oral anticoagulants. Thromb Res., vol. 131 (3), pp. 279–80.
15. Xarelto®. Available at: https://www.rlsnet.ru/tn_index_id_43277.htm (accessed 25 February 2018)
16. Instruktsiya po meditsinskomu primeneniyu preparata Pradaksa [Summary of product characteristics of medicine Pradaxa]. Available at: http://www.rceth.by/NDfiles/instr/8992_09_10_14_15_16_17_i.pdf (accessed 25 February 2018)
17. Budnitz D.S., Lovegrove M.C., Shehab N., Richards C.L. (2011) Emergency hospitalizations for adverse drug events in older Americans. N Eng J Med., vol. 365, pp. 200–2012.
18. Ruff C.T., Giugliano R.P., Braunwald E. et al. (2014) Comparison of the effi cacy and safety of new oral anticoagulants with warfarin in patients with atrial fi brillation: a meta-analysis of randomised trials. Lance, vol. 383 (9921), pp. 955–962.
19. Van der Hulle T., Kooiman J., Den Exter P.L. et al. (2014) Eff ectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost., vol. 12 (3), pp. 320–328.
20. Kaatz S., Kouides P.A., Garcia D.A. et al. (2012) Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol., vol. 87, pp. 141–145.
21. Miesbach W., Seifried E. (2012) New direct oral anticoagulants-current therapeutic options and treatment recommendations for bleeding complications. Thromb Haemost., vol. 108, pp. 625–632.
22. Levy J.H., Ageno W., Chan N.C., Crowther M. (2016) When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH. J Thromb. Haemost., vol. 14, pp. 623–627.
23. Glund S., Stangier J., Schmohl M. et al. (2015) Safety, tolerability, and effi cacy of idarucizumab for the reversal of the anticoagulant eff ect of dabigatran in healthy male volunteers: a randomized, placebo-controlled, double-blind phase 1 trial. Lancet, vol. 386, pp. 680–690.
24. Schiele F., van Ryn J., Canada K. et al. (2014) A specifi c antidote for dabigatran: functional and structural characterization. Blood, vol. 121 (18), pp. 3554–3562.
25. Becker R.C. (2016) The biochemistry, enzymology and pharmacology of non-vitamin K anticoagulant drug reversal agents and antidotes. J Thromb Thrombolysis, vol. 41, pp. 273–278.
26. Frontera J.A., Lewin III J.J., Rabinstein A.A. et al. (2016) Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage. Neurocrit Care, vol. 24 (1), pp. 6–46.
27. Kakkar Ajay K., Mueller Iris (2013) Risk Profi les and Antithrombotic Treatment of Patients Newly Diagnosed with Atrial Fibrillation at Risk of Stroke: Perspectives from the International, Observational, Prospective GARFIELD Registry. PLOS ONE, vol. 8, Is. 5, p. e63479.
28. Marinigh R., Lip G.Y.H., Fiotti N. (2010) Age as a risk factor for stroke in atrial fi brillation patients: Implications for thromboprophylaxis. J Am Coll Cardiol, vol. 56, pp. 827–837.
29. Zalesak M., Siu K., Francis K., et al. (2013) Higher persistence in newly diagnosed nonvalvular atrial fi brillation patients treated with dabigatran versus warfarin. Circ Cardiovasc Qual Outcomes, vol. 6, pp. 567–74.
30. Kirchhof P., Benussi S., Kotecha D., et al. 2016 ESC Guidelines for the management of atrial fi brillation developed in collaboration with EACTS. European Heart Journal. Available at: http://eurheartj.oxfordjournals.org/content/early/2016/08/26/eurheartj.ehw210 (accessed 25 February 2018)
31. Olesen J.B., Lip G.Y., Hansen M.L., et al. (2011) Validation of risk stratifi cation schemes for predicting stroke and thromboembolism in patients with atrial fi brillation: nationwide cohort study. BMJ, vol. 342, pp. d124.
32. Van de Werf F, Bax J, Betriu A et al., for the ESC Committee for Practice Guidelines (2010) Guidelines for the management of atrial fi brillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J., vol. 31, pp. 2369–429.
33. Gadsbell K. (2017) Increased use of oral anticoagulants in patients with atrial fi brillation: temporal trends from 2005 to 2015 in Denmark. EHJ, vol. 38, pp. 899–906.
34. Xiong Q., Lau Y.C., Senoo K. et al. (2015) Non-vitamin K antagonist oral anticoagulants (NOACs) in patients with concomitant atrial fi brillation and heart failure: a systemic review and meta-analysis of randomized trials. Eur J Heart Fail., vol. 17 (11), pp. 1192–200.
35. Connolly S., Parekh A., Reilly P .A., et al. (2009) Rationale and design of RE-LY: randomized evaluation of longterm anticoagulant therapy, warfarin, compared with dabigatran. Am Heart J ., vol. 157 (5), pp. 805–10.
36. ROCKET AF Study Investigators (2010). Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationa le and design of the ROCKET AF study. Am Heart J., vol. 159 (3), pp. 340–347.
37. (2011) Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fi brillation trial. Available at: http://www.anticoagulant-trials.eu/studies-a-z/detail/study/aristotle.html (accessed 2 5 February 2018)
38. Larsen T.B. et al. (2014) Bleeding events among new starters and switchers to dabigatran compared with warfarin in atrial fi brillation. Am J Med., vol. 127 (7), pp. 650–656.
39. Reichman D.J., Wernecke M.E. (2016) Stroke, bleeding, and mortality risks in elderly medicare benefi ciaries treated with dabigatran or rivaroxaban for nonvalvular atrial fi brillation JAMA, vol. 315, pp. 2117–2118.
40. Diener C. (2017) Choosing a particular oral anticoagulant and dose for stroke prevent in individual patients with nonvalvular atrial fi brillation: part 2. EHJ, vol. 38, pp. 860–868.
41. Rekomendatsii ESC po diagnostike i vedeniyu patsientov s ostroi emboliei sistemi legochnoi arterii 2014 [ESC recommendations on d iagnostics and maintaining of patients with acute pulmonary embolism 2014]. Available at: http://scardio.ru/content/Guidelines/Recom%20embolia%208_rkj_1.pdf (accessed 25 February 2018).
42. Voigtlaender M., Langer F. (2017) Direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism. What do we know so f ar? Hamostaseologie, vol. 37 (4), pp. 241–255.
43. Habib G., Lancellotti P., Antunes M.J. et al. (2015) ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Assoc iation for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J., vol. 36 (44), pp. 3075–128.
44. Zamorano J.L., Lancellotti P., Rodrigu ez Muñoz D. 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 fo r cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J., vol. 37 (36), pp. 2768–2801.
