Advanced search

Vol 81, Supp. I (2023): Zeszyty Edukacyjne 1/2023
Opinie i stanowiska ekspertów
Published online: 2023-09-27

open access

View PDF (Polish) Download PDF file
Page views 292
Article views/downloads 172
Get Citation

Connect on Social Media

Connect on Social Media

Stanowisko ekspertów Polskiego Towarzystwa Kardiologicznego dotyczące stosowania andeksanetu alfa w warunkach polskich — interdyscyplinarny protokół

Ewelina Kazimierczyk1, Milena Dąbrowska2, Marek Gierlotka3, Katarzyna Kapica-Topczewska4, Bartosz Karaszewski5, Adam Kobayashi6, Zbigniew Krasiński7, Jacek Kubica8, Alina Kułakowska4, Krzysztof Kurek9, Robert Ładny10, Eliza Pleban11, Konrad Rejdak12, Grażyna Rydzewska13, Agnieszka Słowik14, Piotr Szopiński11, Arkadiusz Woźniak15, Agnieszka Tycińska1
DOI: 10.33963/v.kp.96509

Abstract

Andeksanet alfa (AA) jest rekombinowanym, nieaktywnym analogiem ludzkiego czynnika Xa (FXa), skutecznie odwracającym działanie jego inhibitorów — dostępnych w Polsce rywaroksabanu i apiksabanu. Lek otrzymał rejestrację po opublikowaniu wyników badania ANNEXA-4 (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors 4), w którym udowodniono jego skuteczność w przywracaniu hemostazy w zagrażających życiu krwawieniach w grupie pacjentów stosujących te leki przeciwkrzepliwe. Dlatego AA jest obecnie zalecany u pacjentów stosujących terapię apiksabanem lub rywaroksabanem z masywnymi i niemożliwymi do opanowania krwotokami, w tym udarami krwotocznymi i krwawieniami z przewodu pokarmowego. Najodpowiedniejsze do oszacowania stężenia rywaroksabanu i apiksabanu w osoczu, poza jego bezpośrednią oceną, są chromogenne testy anty-Xa specyficzne dla leku. Brak aktywności anty-Xa stwierdzony przy użyciu tych oznaczeń wyklucza istotne klinicznie stężenie inhibitora FXa w osoczu. Dawka AA nie powinna być natomiast modyfikowana na podstawie wyników badań hemostazy. Zależy ona wyłącznie od czasu, jaki upłynął od przyjęcia ostatniej dawki inhibitora FXa, oraz od dawki i rodzaju stosowanego przewlekle leku. Andeksanet alfa podawany jest w postaci bolusa dożylnego a następnie włączony zostaje wlew dożylny leku. Maksymalne odwrócenie aktywności anty-Xa następuje w ciągu 2 minut od zakończenia podawania bolusa, a kontynuowanie ciągłej infuzji dożylnej umożliwia utrzymanie efektu aż do 2 godzin po jego zakończeniu. Ponieważ aktywność leku przeciwkrzepliwego może się pojawić ponownie po zakończeniu wlewu, obecnie nie jest jasne, w jakim momencie po podaniu AA można (ponownie) podać inhibitory FXa lub heparynę.

Keywords: andeksanet alfaantidotumapiksabandoustne antykoagulanty niebędące antagonistami witaminy Kkrwawienierywaroksaban

Article available in PDF format

View PDF (Polish) Download PDF file

References

  1. Steffel J, Collins R, Antz M, et al. 2021 European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Europace. 2021; 23(10): 1612–1676.
    CrossRefPubMed
  2. Milling TJJr, Middeldorp S, Xu L, et al. Final study report of andexana for major bleeding with factor Xa inhibitors. Circulation. 2023; 147(13): 1026–1038.
    CrossRefPubMed
  3. Mutscher E, Geisslinger G, Kroeme HK, Menzel S, Ruth P. Farmakologia i toksykologia. Wyd. IV. MedPharm Polska, Wrocław 2013.
  4. Douxfils J, Adcock DM, Bates SM, et al. International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost. 2018; 118(3): 437–450.
    CrossRefPubMed
  5. Gorczyca-Głowacka I, Kapłon-Cieślicka A, Wełnicki M, et al. Rules for using reduced doses of non-vitamin K antagonist oral anticoagulants in the prevention of thromboembolic complications in patients with atrial fibrillation. The expert opinion of the Working Group on Cardiovascular Pharmacotherapy of the Polish Cardiac Society. Kardiol Pol. 2022; 80(12): 1299–1306.
    CrossRefPubMed
  6. Douxfils J, Adcock DM, Bates SM, et al. 2021 update of the International Council for Standardization in Haematology recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost. 2021; 121(8): 1008–1020.
    CrossRefPubMed
  7. Levy JH, Ageno W, Chan NC, et al. When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH. J Thromb Haemost. 2016; 14(3): 623–627.
    CrossRefPubMed
  8. Akpan IJ, Cuker A. Laboratory assessment of the direct oral anticoagulants: who can benefit? Kardiol Pol. 2021; 79(6): 622–630.
    CrossRefPubMed
  9. Hutt Centeno E, Militello M, Gomes MP. Anti-Xa assays: What is their role today in antithrombotic therapy? Cleve Clin J Med. 2019; 86(6): 417–425.
    CrossRefPubMed
  10. Lu G, DeGuzman FR, Hollenbach SJ, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013; 19(4): 446–451.
    CrossRefPubMed
  11. Pine PR, Hollenbach SJ, Tan S, et al. Andexanet alfa reverses edoxaban-induced anticoagulation in a rabbit liver laceration model of acute bleeding. Presented at the European Society of Cardiology Congress. London, United Kingdom, 29 August–2 September 2015.
  12. Lu G, Conley PB, Leeds JM, et al. A phase 2 PK/PD study of andexanet alfa for reversal of rivaroxaban and edoxaban anticoagulation in healthy volunteers. Blood Adv. 2020; 4(4): 728–739.
    CrossRefPubMed
  13. Siegal D, Lu G, Leeds JM, et al. Safety, pharmacokinetics, and reversal of apixaban anticoagulation with andexanet alfa. Blood Adv. 2017; 1(21): 1827–1838.
    CrossRefPubMed
  14. Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015; 373(25): 2413–2424.
    CrossRefPubMed
  15. Bradshaw PG, Keegan SP, Droege ME, et al. Reversal of apixaban and rivaroxaban with andexanet alfa prior to invasive or surgical procedures. Pharmacotherapy. 2022; 42(10): 780–791.
    CrossRefPubMed
  16. Brown CS, Scott RA, Sridharan M, et al. Real-world utilization of andexanet alfa. Am J Emerg Med. 2020; 38(4): 810–814.
    CrossRefPubMed
  17. European Medicines Agency AaSoPC. https://www.ema.europa. eu/en/documents/product-information/ondexxya-epar-product-in- formation_en.pdf (September 12, 2020).
  18. Liu J, Elsamadisi P, Philips E, et al. Four-factor prothrombin complex concentrate plus andexanet alfa for reversal of factor Xa inhibitor-associated bleeding: Case series. Am J Health Syst Pharm. 2022; 79(16): 1323–1329.
    CrossRefPubMed
  19. Bradshaw PG, Keegan S, Foertsch M, et al. Andexanet alfa after 4-factor PCC administration for intracranial hemorrhage: a case series. J Thromb Thrombolysis. 2022; 54(2): 295–300.
    CrossRefPubMed
  20. Watson CJ, Zettervall SL, Hall MM, et al. Difficult Intraoperative Heparinization Following Andexanet Alfa Administration. Clin Pract Cases Emerg Med. 2019; 3(4): 390–394.
    CrossRefPubMed
  21. Eche IM, Elsamadisi P, Wex N, et al. Intraoperative unfractionated heparin unresponsiveness during endovascular repair of a ruptured abdominal aortic aneurysm following administration of andexanet alfa for the reversal of rivaroxaban. Pharmacotherapy. 2019; 39(8): 861–865.
    CrossRefPubMed
  22. Greenberg SM, Ziai WC, Cordonnier C, et al. 2022 guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association/American Stroke Association. Stroke. 2022; 53(7): e282–e361.
    CrossRefPubMed
  23. Jolink WMT, Klijn CJM, Brouwers PJ, et al. Time trends in incidence, case fatality, and mortality of intracerebral hemorrhage. Neurology. 2015; 85(15): 1318–1324.
    CrossRefPubMed
  24. Flaherty ML, Kissela B, Woo D, et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology. 2007; 68(2): 116–121.
    CrossRefPubMed
  25. Hankey GJ. Intracranial hemorrhage and novel anticoagulants for atrial fibrillation: what have we learned? Curr Cardiol Rep. 2014; 16(5): 480.
    CrossRefPubMed
  26. Patel MR, Mahaffey KW, Garg J, et al. ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011; 365(10): 883–891.
    CrossRefPubMed
  27. Granger CB, Alexander JH, McMurray JJV, et al. ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011; 365(11): 981–992.
    CrossRefPubMed
  28. Wu T, Lv C, Wu L, et al. Risk of intracranial hemorrhage with direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials. J Neurol. 2022; 269(2): 664–675.
    CrossRefPubMed
  29. Flaherty ML, Haverbusch M, Sekar P, et al. Location and outcome of anticoagulant-associated intracerebral hemorrhage. Neurocrit Care. 2006; 5(3): 197–201.
    CrossRefPubMed
  30. Troyer C, Nguyen W, Xie A, et al. Retrospective review of andexanet alfa versus 4-factor prothrombin complex concentrate for reversal of doac-associated intracranial hemorrhage. J Thromb Thrombolysis. 2023; 55(1): 149–155.
    CrossRefPubMed
  31. Kuramatsu JB, Gerner ST, Schellinger PD, et al. Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage. JAMA. 2015; 313(8): 824–836.
    CrossRefPubMed
  32. Demchuk AM, Yue P, Zotova E, et al. Hemostatic efficacy and anti-FXa (factor Xa) reversal with andexanet alfa in intracranial hemorrhage: ANNEXA-4 substudy. Stroke. 2021; 52(6): 2096–2105.
    CrossRefPubMed
  33. Barra ME, Das AS, Hayes BD, et al. Evaluation of andexanet alfa and four-factor prothrombin complex concentrate (4F-PCC) for reversal of rivaroxaban- and apixaban-associated intracranial hemorrhages. J Thromb Haemost. 2020; 18(7): 1637–1647.
    CrossRefPubMed
  34. Vestal ML, Hodulik K, Mando-Vandrick J, et al. Andexanet alfa and four-factor prothrombin complex concentrate for reversal of apixaban and rivaroxaban in patients diagnosed with intracranial hemorrhage. J Thromb Thrombolysis. 2022; 53(1): 167–175.
    CrossRefPubMed
  35. Giovino A, Shomo E, Busey KV, et al. An 18-month single-center observational study of real-world use of andexanet alfa in patients with factor Xa inhibitor associated intracranial hemorrhage. Clin Neurol Neurosurg. 2020; 195: 106070.
    CrossRefPubMed
  36. Costa OS, Connolly SJ, Sharma M, et al. Andexanet alfa versus four-factor prothrombin complex concentrate for the reversal of apixaban- or rivaroxaban-associated intracranial hemorrhage: a propensity score-overlap weighted analysis. Crit Care. 2022; 26(1): 180.
    CrossRefPubMed
  37. Ammar AA, Ammar MA, Owusu KA, et al. Andexanet alfa versus 4-factor prothrombin complex concentrate for reversal of factor Xa inhibitors in intracranial hemorrhage. Neurocrit Care. 2021; 35(1): 255–261.
    CrossRefPubMed
  38. Pham H, Medford WG, Horst S, et al. Andexanet alfa versus four-factor prothrombin complex concentrate for the reversal of apixaban- or rivaroxaban-associated intracranial hemorrhages. Am J Emerg Med. 2022; 55: 38–44.
    CrossRefPubMed
  39. Parsels KA, Seabury RW, Zyck S, et al. Andexanet alfa effectiveness and safety versus four-factor prothrombin complex concentrate (4F-PCC) in intracranial hemorrhage while on apixaban or rivaroxaban: A single-center, retrospective, matched cohort analysis. Am J Emerg Med. 2022; 55: 16–19.
    CrossRefPubMed
  40. Lipski M, Pasciolla S, Wojcik K, et al. Comparison of 4-factor prothrombin complex concentrate and andexanet alfa for reversal of apixaban and rivaroxaban in the setting of intracranial hemorrhage. J Thromb Thrombolysis. 2023; 55(3): 519–526.
    CrossRefPubMed
  41. Chaudhary R, Singh A, Chaudhary R, et al. Evaluation of direct oral anticoagulant reversal agents in intracranial hemorrhage. JAMA Network Open. 2022; 5(11): e2240145.
    CrossRefPubMed
  42. Nederpelt CJ, Naar L, Krijnen P, et al. Andexanet alfa or prothrombin complex concentrate for factor xa inhibitor reversal in acute major bleeding: a systematic review and meta-analysis. Crit Care Med. 2021; 49(10): e1025–e1036.
    CrossRefPubMed
  43. Alexion Pharmaceuticals : Trial of andexanet in ICH patients receiving an oral FXa inhibitor. ClinicalTrials.gov Identifier NCT03661528. September 9, 2022. https://clinicaltrials.gov/ct2/show/NCT03661528 (October 9, 2022).
  44. Veitch AM, Radaelli F, Alikhan R, et al. Endoscopy in patients on antiplatelet or anticoagulant therapy: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guideline update. Gut. 2021; 70(9): 1611–1628.
    CrossRefPubMed
  45. Gralnek IM, Stanley AJ, Morris AJ, et al. Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) Guideline — update 2021. Endoscopy. 2021; 53(3): 300–332.
    CrossRefPubMed
  46. Connolly SJ, Milling TJJr, Eikelboom JW, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016; 375(12): 1131–1141.
    CrossRefPubMed
  47. Gralnek IM, Camus Duboc M, Garcia-Pagan JC, et al. Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2022; 54(11): 1094–1120.
    CrossRefPubMed
  48. Triantafyllou K, Gkolfakis P, Gralnek IM, et al. Diagnosis and management of acute lower gastrointestinal bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2021; 53(8): 850–868.
    CrossRefPubMed
  49. Abraham NS, Barkun AN, Sauer BG, et al. American College of Gastroenterology-Canadian Association of Gastroenterology Clinical Practice Guideline: management of anticoagulants and antiplatelets during acute gastrointestinal bleeding and the periendoscopic period. Am J Gastroenterol. 2022; 117(4): 542–558.
    CrossRefPubMed
  50. Rozporządzenie Ministra Zdrowia z dnia 10 maja 2002 r. w sprawie szpitalnego oddziału ratunkowego. https://www.prawo.pl/akty/dz-u-2002-74-687,16964620.html (June 27, 2023).
  51. Kuliczkowski W, Gierlotka M, Tycińska A, et al. Postępowanie w krwawieniach u pacjentów hospitalizowanych na oddziale intensywnej terapii kardiologicznej. Opinia Zespołu Ekspertów Asocjacji Intensywnej Terapii Kardiologicznej oraz Sekcji Farmakoterapii Sercowo‐Naczyniowej Polskiego Towarzystwa Kardiologicznego we współpracy ze specjalistami z innych dziedzin medycyny. Zeszyty Edukacyjne Kardiol Pol. 2020; 78(1): 88–115.
  52. Undas A, Drabik L, Potpara T. Krwawienie u chorych z migotaniem przedsionków leczonych przeciwkrzepliwie: uwagi praktyczne. Zeszyty Edukacyjne Kardiol Pol. 2020; 78(3): 136–152.
  53. Tomaselli GF, Mahaffey KW, Cuker A, et al. 2017 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the American College of Cardiology Task Force on expert consensus decision pathways. J Am Coll Cardiol. 2017; 70(24): 3042–3067.
    CrossRefPubMed
  54. Majeed A, Ågren A, Holmström M, et al. Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study. Blood. 2017; 130(15): 1706–1712.
    CrossRefPubMed
  55. Schulman S, Gross PL, Ritchie B, et al. Prothrombin complex concentrate for major bleeding on factor Xa inhibitors: a prospective cohort study. Thromb Haemost. 2018; 118: 842–51.
    CrossRefPubMed
  56. Gerner ST, Kuramatsu JB, Sembill JA, et al. Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage. Ann Neurol. 2018; 83(1): 186–196.
    CrossRefPubMed
  57. Arachchillage DRJ, Alavian S, Griffin J, et al. Efficacy and safety of prothrombin complex concentrate in patients treated with rivaroxaban or apixaban compared to warfarin presenting with major bleeding. Br J Haematol. 2019; 184(5): 808–816.
    CrossRefPubMed
  58. Lu G, DeGuzman FR, Hollenbach SJ, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013; 19(4): 446–451.
    CrossRefPubMed
  59. Schmidt LE, Hinton MS, Martin ND. Real-world reversal of factor xa inhibition in the setting of major life-threatening bleeding or urgent surgery. J Pharm Pract. 2022 [Epub ahead of print]: 8971900221125516.
    CrossRefPubMed
  60. Milling TJ, King B, Yue P, et al. ANNEXA-4 Investigators. Restart of anticoagulant therapy and risk of thrombosis, rebleeding, and death after factor Xa inhibitor reversal in major bleeding patients. Thromb Haemost. 2021; 121(8): 1097–1106.
    CrossRefPubMed
  61. Halvorsen S, Mehilli J, Cassese S, et al. et al.. 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery. Eur Heart J. 2022; 43(39): 3826–3924.
    CrossRefPubMed
  62. Kainz M, Bsuchner P, Schellongowski P, et al. Intraoperative off-label reversal of apixaban by andexanet alfa while on VA-ECMO immediately after emergent surgery for acute type a aortic dissection. J Cardiothorac Vasc Anesth. 2021; 35(1): 262–264.
    CrossRefPubMed
  63. Portola Netherlands, B.V. in Agreement with the European Medicines Agency and the National Competent Authority. Ondexxya (Andexanet Alfa): Commercial Anti-FXa Activity Assays are Unsuitable for Measuring Anti-FXa Activity Following Administration of Andexanet Alfa. Communication to Healthcare Professional 2020.
  64. Flaherty D, Connors JM, Singh S, et al. Andexanet alfa for urgent reversal of apixaban before aortic surgery requiring cardiopulmonary bypass: a case report. A A Pract. 2019; 13(7): 271–273.
    CrossRefPubMed
  65. Philpott CD, Ernst NE, Makley AT, et al. Case report: extended duration andexanet alfa infusion in a surgical trauma patient. J Pharm Pract. 2022; 36(4): 1002–1007.
    CrossRef
  66. Portola gets FDA breakthrough therapy status for andexanet alfa. 2013. https://www.pharmaceutical-technology.com/uncategorized/newsportola-gets-fda-breakthrough-therapy-status-for-andexanet-alfa/ (June 27, 2023).
  67. FDA (2018) Summary Basis for Regulatory Action. https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/May-3--2018-Summary-Basis-for-Regulatory-Action---ANDEXXA.pdf (June 27, 2023).
  68. Cuker A, Burnett A, Triller D, et al. Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum. Am J Hematol. 2019; 94(6): 697–709.
    CrossRefPubMed
  69. Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018; 2(22): 3257–3291.
    CrossRefPubMed
  70. Christensen H, Cordonnier C, Kõrv J, et al. European Stroke Organisation guideline on reversal of oral anticoagulants in acute intracerebral haemorrhage. Eur Stroke J. 2019; 4(4): 294–306.
    CrossRefPubMed
  71. Tomaselli GF, Mahaffey KW, Cuker A, et al. 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2020; 76(5): 594–622.
    CrossRefPubMed
  72. Lip GYH, Banerjee A, Boriani G, et al. Antithrombotic therapy for atrial fibrillation. Chest. 2018; 154(5): 1121–1201.
    CrossRef
  73. Baugh CW, Levine M, Cornutt D, et al. Anticoagulant reversal strategies in the emergency department setting: recommendations of a multidisciplinary expert panel. Ann Emerg Med. 2020; 76(4): 470–485.
    CrossRefPubMed
  74. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2019; 74(1): 104–132.
    CrossRefPubMed
  75. Chao TF, Joung B, Takahashi Y, et al. 2021 Focused update of the 2017 consensus guidelines of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation. J Arrhythm. 2021; 37(6): 1389–1426.
    CrossRefPubMed
  76. Steiner T, Unterberg A. Treatment of spontaneous intracerebral bleeding, S2k guidelines, 2021, in: German Society for Neurology (Ed.), Guidelines for Diagnostics and Therapy in Neurology. https://dgn.org/leitlinien/ (October 6, 2022).
  77. Ono K, Iwasaki YK, Akao M, et al. JCS/JHRS 2020 guideline on pharmacotherapy of cardiac arrhythmias. Circ J. 2022; 86(11): 1790–1924.
    CrossRefPubMed
  78. Carballo Álvarez F, Albillos Martínez A, Llamas Silero P, et al. Consensus document of the Spanish Society of Digestives Diseases and the Spanish Society of Thrombosis and Haemostasis on massive nonvariceal gastrointestinal bleeding and direct-acting oral anticoagulants. Rev Esp Enferm Dig. 2022; 114(7): 375–389.
    CrossRefPubMed

About cookies

Necessary cookies

Allways active

These cookies are necessary for the proper display and operation of the website. Blocking them may cause the website to malfunction.

Analytical cookies

As part of our website, we use analytical tools, such as Google Analytics, that allow us to verify website traffic. These tools may require the use of cookies.

Community cookies

These are cookies associated with the social networks we use. Accepting them will allow us to associate your visit to the site with our social media profiles.

Marketing cookies

These are cookies responsible for carrying out advertising and marketing activities - consenting to their use will allow us to target you with advertisements based on your previous activities within our website.

Polish Heart Journal (Kardiologia Polska)

About Via Medica Advertising
Bookstore (Ikamed) TVMed
News
Copyright © 2023 Via Medica Regulations Cookie policy Privacy policy Legal Notice