Direktni oralni antikoagulansi – novo poglavlje u antikoagulantnoj terapiji

  • Radica Stepanović-Petrović Univerzitet u Beogradu - Farmaceuski fakultet, Katedra za farmakologiju
  • Katarina Nastić Univerzitet u Beogradu - Farmaceuski fakultet, Katedra za farmakologiju
Ključne reči: direktni oralni antikoagulansi, dabigatran, rivaroksaban, apiksaban, edoksaban, betriksaban

Sažetak


Tromboembolijski događaji predstavljaju vodeći uzrok morbiditeta i mortaliteta širom sveta. Od druge polovine 20. veka, antagonisti vitamina K (VKA), varfarin i acenokumarol bili su jedini dostupni oralni antikoagulantni lekovi. Pojava direktnih oralnih antikoagulanasa (DOAK), od pre 10-tak godina, donela je veliku promenu u antikoagulantnoj terapiji. Direktni inhibitor trombina (dabigatran) i direktni inhibitori faktora Xa (rivaroksaban, apiksaban, edoksaban i betriksaban) su pokazali povoljan odnos koristi i rizika. U poređenju sa varfarinom, DOAK pokazuju predvidljiv farmakokinetički profil, nižu incidencu ozbiljnog krvarenja posebno intrakranijalnog krvarenja i stupaju u mali broj interakcija sa drugim lekovima. Pored toga, DOAK imaju brz nastup dejstva i pokazali su komparabilnu efikasnost u poređenju sa varfarinom i niskomolekularnim heparinima (LMWH) u kliničkim ispitivanjima. Posledično, DOAK postepeno zamenjuju VKA i LMWH u mnogim indikacijama uključujući prevenciju moždanog udara i sistemskog embolizma kod pacijenata sa nevalvularnom atrijalnom fibrilacijom, prevenciju i terapiju venskog tromboembolizma, kao i tromboprofilaksu nakon ugradnje veštačkog kolena/kuka. Dodatno, rivaroksaban (sa aspirinom ili kombinacijom aspirina i klopidogrela) je indikovan u prevenciji aterotrombotičnih događaja posle akutnog koronarnog sindroma, kod pacijenata sa povećanim srčanim biomarkerima. U slučaju pojave ozbiljnog krvarenja, dostupni su antidoti; idarucizumab za dabigatran i andeksanet alfa za rivaroksaban i apiksaban.

Reference

Morin DP, Bernard ML, Madias C, Rogers PA, Thihalolipavan S, Estes NA. The State of the Art: Atrial Fibrillation Epidemiology, Prevention, and Treatment. Mayo Clin Proc. 2016;91(12):1778-1810.

Bruni-Fitzgerald KR. Venous thromboembolism: An overview. J Vasc Nurs. 2015;33(3):95-9.

Wendelboe AM, Raskob GE. Global Burden of Thrombosis: Epidemiologic Aspects Circ Res. 2016;118(9):1340-7

Weitz JI, Harenberg J. New developments in anticoagulants: Past, present and future. Thromb Haemost. 2017;117(7):1283-1288.

Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005;165(10):1095-106.

Weitz JI, Eikelboom JW, Samama MM. New antithrombotic drugs: Antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012; 141: e120S-151S.

Kustos SA, Fasinu PS. Direct-Acting Oral Anticoagulants and Their Reversal Agents—An Update. Medicines (Basel). 2019; 6(4): 103.

Riva N, Ageno W. Pros and cons of vitamin K antagonists and non-vitamin K antagonist oral anticoagulants. Semin Thromb Hemost. 2015;41(2):178-87.

Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018; 39(16):1330-1393.

Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014 Mar 15;383(9921):955-62.

van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood. 2014;124:1968-1975.

Joint Formulary Committee. British National Formulary. 78. London: BMJ Group and Pharmaceutical Press; 2019.

Brayfield A. Martindale The Complete Drug Reference, 39th ed., Pharmaceutical Press. London, 2017

Summary of Product Characteristics – Pradaxa (dabigatran etexilate) [Internet]. Europian Medicines Agency [cited 2020 aug 18] Available from: https://www.ema.europa.eu/en/documents/product-information/pradaxa-epar-product-information_en.pdf

Ashrafi F, Rezaie N, Mousavi S. New Indications for Dabigatran: A Suggestion from a Drug Use Evaluation Study. J Res Pharm Pract. 2017; 6(4): 211–216.

Blair HA, Keating GM. Dabigatran Etexilate: A Review in Nonvalvular Atrial Fibrillation. Drugs. 2017;77(3):331-344.

Stangier J, Rathgen K, Stähle H, Gansser D, Roth W. The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol. 2007; 64: 292–303.

Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation.N Engl J Med. 2009;361:1139–1151.

Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L. Randomized Evaluation of Long-Term Anticoagulation Therapy Investigators. Newly identified events in the RE-LY trial. N Engl J Med. 2010;363:1875–1876.

Kaatz S, Ahmad D , Spyropoulos A C, Schulman S, Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost. 2015;13:2119-26.

Yavuz B, Ayturk M, Ozkan S, Ozturk M, Topaloglu C, Aksoy H, et al. A real world data of dabigatran etexilate: multicenter registry of oral anticoagulants in nonvalvular atrial fibrillation. J Thromb Thrombolysis. 2016;42(3):399–404.

Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013;368(8):709-18.

Burness CB, McKeage K. Dabigatran etexilate: a review of its use for the prevention of venous thromboembolism after total hip or knee replacement surgery. Drugs. 2012;72(7):963-86.

Summary of Product Characteristics – Praxbind (idarucizumab). [Internet]. Europian Medicines Agency [cited 2020 aug 17] Available from: https://www.ema.europa.eu/en/documents/product-information/praxbind-epar-product-information_en.pdf

Vimalesvaran K, Dockrill SJ, Gorog DA. Role of rivaroxaban in the management of atrial fibrillation: insights from clinical practice. Vasc Health Risk Manag. 2018;14:13–21.

National Institute for Health and Care Excellence: Technology appraisal guidance. Acute coronary syndromes: Rivaroxaban for preventing atherothrombotic events in people with coronary or peripheral artery disease. London: National Institute for Health and Care Excellence (UK); October 2019.

Mueck W, Stampfuss J, Kubitza D, Becka M. Clinical Pharmacokinetic and Pharmacodynamic Profile of Rivaroxaban. Clin Pharmacokinet. 2014; 53(1): 1–16.

Chan NC , Weitz JI. Rivaroxaban for prevention and treatment of venous thromboembolism. Future Cardiol. 2019;15(2):63-77.

Summary of Product Characteristics – Xarelto (rivaroxaban). [Internet]. Europian Medicines Agency [cited 2020 aug 17]. Available from: https://www.ema.europa.eu/en/documents/product-information/xarelto-epar-product-information_en.pdf

Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883–891.

Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, et al. Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). J Clin Oncol. 2018;36(20):2017-2023.

Summary of Product Characteristics – Ondexxya (andexanet alfa). [Internet]. Europian Medicines Agency [cited 2020 aug 18] Available from: https://www.ema.europa.eu/en/documents/product-information/ondexxya-epar-product-information_en.pdf

Summary of Product Characteristics – Eliquis (apixaban). [Internet]. Europian Medicines Agency [cited 2020 aug 17] Available from: https://www.ema.europa.eu/en/documents/product-information/apixaban-accord-epar-product-information_en.pdf

European Medicines Agency. [Internet]. [cited 2020 aug 28]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/apixaban-accord

Greig SL, Garnock-Jones KP. Apixaban: A Review in Venous Thromboembolism. Drugs. 2016;76(15):1493-1504.

Byon W, Garonzik S , Boyd RA, Frost CE. Apixaban: A Clinical Pharmacokinetic and Pharmacodynamic Review. Clin Pharmacokinet. 2019;58(10):1265-1279.

Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–992.

Hylek EM, Held C, Alexander JH, Lopes RD, De Caterina R, Wojdyla DM, et al. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): Predictors, Characteristics, and Clinical Outcomes. J Am Coll Cardiol. 2014;63:2141–2147.

Raskob G E, Gallus A S, Pineo G F, Chen D, Ramirez L-M, Wright R T, et al. Apixaban versus enoxaparin for thromboprophylaxis after hip or knee replacement: pooled analysis of major venous thromboembolism and bleeding in 8464 patients from the ADVANCE-2 and ADVANCE-3 trials. J Bone Joint Surg Br. 2012;94:257-64.

Agnelli G, Becattini C, Meyer G, Muñoz A, Huisman MV, Connors JM, et al. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. N Engl J Med. 2020;382(17):1599-1607.

Poulakos M , Walker JN , Baig U , David T. Edoxaban: A direct oral anticoagulant. Am J Health Syst Pharm. 2017;74(3):117-129.

European Medicines Agency. [Internet]. [cited 2020 aug 28]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/lixiana

Eisen A , Ruff CT. Edoxaban in patients with atrial fibrillation. Ther Adv Cardiovasc Dis. 2017;11(3):81-90.

Corsini A, Ferri N, Proietti M, Boriani G. Edoxaban and the Issue of Drug‑Drug Interactions: From Pharmacology to Clinical Practice. Drugs. 2020;80(11):1065-1083.

Ruff CT, Giugliano RP, Braunwald E, Morrow DA, Murphy SA, Kuder JF, et al. Association between edoxaban dose, concentration, anti-Factor Xa activity, and outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48 trial. Lancet. 2015;385:2288–2295.

Hokusai-VTE Investigators, Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406-15.

Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, et al. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med 2018;378(7):615-624.

Lekura J, Kalus J. Overview of betrixaban and its role in clinical practice. Am J Health Syst Pharm. 2018;75(15):1095-1102.

Huisman MV, Klok FA. Pharmacological properties of betrixaban. Eur Heart J Suppl. 2018;20(Suppl E):E12-E15.

Cannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, et al. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med. 2017;377:1513-1524.

Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med 2016;375:24232434.

Lopes RD, Heizer G, Aronson R, Vora AN, Massaro T, Mehran R, et al. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N Engl J Med 2019;380:15091524

Vranckx P, Valgimigli M, Eckardt L, Tijssen J, Lewalter T, Gargiulo G, et al. Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial. Lancet 2019;394:13351343

Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893-2962.

National Institute for Health and Care Excellence:

Clinical Guidelines. Embolism and thrombosis: Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. London: National Institute for Health and Care Excellence (UK); March 2020.

Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603.

Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med 2013;369(13):1206-14.

Objavljeno
2020/11/05
Rubrika
Pregledni (Revijalni) rad