Extended therapy and secondary prevention of venous thromboembolic complications

Abstract

Venous thromboembolic complications (VTEC) are acute and time-limited diseases. However, the recurrence rate after a first episode of VTEC is high and potentially life-threatening. Developed deep vein thrombosis (DVT) and thromboembolism of pulmonary artery (TEPA) are inevitably associated with use of anticoagulant therapy (ACT). A peculiarity of the modern clinical management of patients with VTEC is determination of duration of ACT.

Aim. To study possibilities of prolonged anticoagulation therapy and secondary prevention of venous thromboembolic complications taking into consideration modern variants of drug therapy, on the basis of literature data.

Search for literature was conducted in Medline and Elibrary databases including materials published in 2020. Randomized clinical and observational studies and meta-analyses, concerning prolonged therapy and secondary prevention of VTEC with vitamin K antagonists (VKA), peroral anticoagulants (POAC), sulodexide and aspirin, were analyzed. As it is evidenced by patho-physiological and epidemiological data, risk of VTEC recurrence in most patients is not resolved after the first 6 months of treatment with anticoagulants. In such situations it is reasonable to prolong anticoagulation for an indefinite period of time. However, sometimes a limiting factor for prolonged therapy with anticoagulants is bleedings caused by prolonged anticoagulation, sometimes leading to lethal outcome. Therefore, duration of treatment in the long-term period after an acute episode may rest on the balance between the risk of development of recurrence of venous thrombosis and bleeding, evaluated with the help of scales. The main achievement of recent years regarding prolonged therapy and secondary prevention of VTEC, are POAC, which in fact are new and alternative drugs that permitted the emergence of serious evidential basis in the range of means for treatment of this category of patients, sulodexide drug has appeared characterized by the minimal rate of development of large and clinically significant bleedings.

Conclusion. The emergence of serious evidential basis for POAC with improved safety profiles, different pharmacokinetic profiles and dosage regimens, including sulodexide that has been actively used in recent years for secondary prevention of VTEC, will permit clinicians to differentially approach treatment of different clinical variants of venous thrombosis, to improve the results of therapy taking into account evaluation of the individual risk and comorbid diseases, and compliance of patients.

Keywords

venous thromboembolic complications / deep vein thrombosis / thromboembolism of pulmonary artery / extended therapy of venous thrombosis / secondary prevention of venous thrombosis / secondary prevention of recurrences / vitamin K antagonists / peroral anticoagulants

References

[1] Heit JA. Epidemiology of venous thromboembolism. Nature Reviews. Cardiology. 2015;12(8):464-74. doi:10.1038/nrcardio.2015.83

[2] Heit J.A. Epidemiology of venous thromboembolism // Nature Reviews. Cardiology. 2015. Vol. 12, №8. Р. 464-474. doi:10.1038/nrcardio.2015.83

[3] Bokeriya LA, Zatevakhin II, Kiriyenko AI, et al. Rossiyskiye klinicheskiye rekomendatsii po diagnostike, lecheniyu i profilaktike venoznykh tromboembolicheskikh oslozhneniy (VTEO). Flebologiya. 2015;9(4-2):1-52. (In Russ).

[4] Бокерия Л.А., Затевахин И.И., Кириенко А.И., и др. Российские клинические рекомендации по диагностике, лечению и профилактике венозных тромбоэмболических осложнений (ВТЭО) // Флебология. 2015. Т. 9, №4-2. С. 1-52.

[5] Polikarpov AV, Aleksandrova GA, Golubev NA, et al. Obshchaya zabolevayemost’ vzroslogo naseleniya Rossii v 2017 godu. In: Statisticheskiy sbornik 2017 god. Moscow; 2018. Suppl. 4. Available at: https://minzdrav.gov.ru/ministry/61/22/stranitsa-979/statisticheskie-i-informatsionnye-materialy/statisti-cheskiy-sbornik-2017-god. Accessed: 2020 July 25. (In Russ).

[6] Поликарпов А.В., Александрова Г.А., Голубев Н.А., и др. Общая заболеваемость взрослого населения России в 2017 году. В сб.: Статистический сборник 2017 год. М.; 2018. Ч. 4. До-ступно по: https://minzdrav.gov.ru/ministry/61/22/stranitsa-979/statisticheskie-i-informatsionnye-materialy/sta-tisticheskiy-sbornik-2017-god. Ссылка активна на 20 июля 2020.

[7] Heit JA, Mohr DN, Silverstein MD, et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Archives of Internal Medicine. 2000; 160(60): 761-8. doi:10.1001/archinte.160.6.761

[8] Heit J.A., Mohr D.N., Silverstein M.D., et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a populationbased cohort study // Archives of Internal Medicine. 2000. Vol. 160, №60. Р. 761-768. doi:10.1001/archinte.160.6.761

[9] Kyrle PA, Kammer M, Eischer L, et al. The long-term recurrence risk of patients with unprovoked venous thromboembolism: an observational cohort study. Journal of Thrombosis and Haemostasis. 2016;14(12):2402-9. doi:10.1111/jth.13524

[10] Kyrle P.A., Kammer M., Eischer L., et al. The longterm recurrence risk of patients with unprovoked venous thromboembolism: an observational cohort study // Journal of Thrombosis and Haemostasis. 2016. Vol. 14, №12. Р. 2402-2409. doi:10.1111/jth.13524

[11] Prandoni P, Lensing AWA, Prins MH, et al. Residual venous thrombosis as a predictive factor of recurrent venous thromboembolism. Annals of Internal Medicine. 2002;137(12):955-60. doi:10.7326/0003-4819-137-12-200212170-00008

[12] Prandoni P., Lensing A.W.A., Prins M.H., et al. Residual venous thrombosis as a predictive factor of recurrent venous thromboembolism // Annals of Internal Medicine. 2002. Vol. 137, №12. Р. 955-960. doi:10.7326/0003-4819-137-12-200212170-00008

[13] Prandoni P, Noventa F, Ghirarduzzi A, et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica. 2007;92(2):199-205. doi:10.3324/ haematol.10516

[14] Prandoni P., Noventa F., Ghirarduzzi A., et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients // Haematologica. 2007. Vol. 92, №2. Р. 199-205. doi:10.3324/haematol.10516

[15] Kyrle PA, Rosendaal FR, Eichinger S. Risk assessment for recurrent venous thrombosis. Lancet. 2010;376(9757):2032-9. doi:10.1016/S0140-6736(10)60962-2

[16] Kyrle P.A., Rosendaal F.R., Eichinger S. Risk assessment for recurrent venous thrombosis // Lancet. 2010. Vol. 376, №9757. Р. 2032-2039. doi:10.1016/S0140-6736(10)60962-2

[17] Verso M, Agnelli G, Ageno W, et al. Long-term death and recurrence in patients with acute venous thromboembolism: the MASTER registry. Thrombosis Research. 2012;130(3):369-73. doi:10.1016/j.thromres.2012.04.003

[18] Verso M., Agnelli G., Ageno W., et al. Longterm death and recurrence in patients with acute venous thromboembolism: the MASTER registry // Thrombosis Research. 2012. Vol. 130, №3. Р. 369-373. doi:10.1016/j.thromres.2012.04.003

[19] Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease. Chest. 2016;149(2): 315-52. doi:10.1016/j.chest.2015.11.026

[20] Kearon C., Akl E.A., Ornelas J., et al. Antithrombotic Therapy for VTE Disease // Chest. 2016. Vol. 149, №2. Р. 315-352. doi:10.1016/j.chest.2015.11.026

[21] Mearns ES, Coleman CI, Patel D, et al. Index clinical manifestation of venous thromboembolism predicts early recurrence type and frequency: a meta-analysis of randomized controlled trials. Journal of Thrombosis and Haemostasis. 2015;13(6):1043-52. doi:10.1111/jth.12914

[22] Mearns E.S., Coleman C.I., Patel D., et al. Index clinical manifestation of venous thromboembolism predicts early recurrence type and frequency: a metaanalysis of randomized controlled trials // Journal of Thrombosis and Haemostasis. 2015. Vol. 13, №6. Р. 1043-1052. doi:10.1111/jth.12914

[23] Kyrle PA, Eichinger S. The risk of recurrent venous thromboembolism: the Austrian Study on Recurrent Venous Thromboembolism. Wiener Klinische Wochenschrift. 2003;115(13-14):471-4. doi:10.1007/BF03041030

[24] Kyrle P.A., Eichinger S. The risk of recurrent venous thromboembolism: the Austrian Study on Recurrent Venous Thromboembolism // Wiener Klinische Wochenschrift. 2003. Vol. 115, №13-14. Р. 471-474. doi:10.1007/BF03041030

[25] Iorio A, Kearon C, Filippucci E, et al. Risk of

[26] Iorio A., Kearon C., Filippucci E., et al. Risk of recurrence after a first episode of symptomatic venous thromboembolism provoked by a transient risk factor: a systematic review // Archives of Internal Medicine. 2010. Vol. 170, №19. Р. 1710-1716. doi:10.1001/archinternmed.2010.367

[27] recurrence after a first episode of symptomatic

[28] Boutitie F., Pinede L., Schulman S., et al. Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants' data from seven trials // BMJ. 2011. Vol. 342. Р. d3036. doi:10.1136/bmj.d3036

[29] venous thromboembolism provoked by a transient risk factor: a systematic review. Archives of Internal Medicine. 2010;170(19):1710-6. doi:10.1001/archinternmed.2010.367

[30] Kearon C., Akl E.А., Comerota A.J., et al. Antithrombotic Therapy for VTE Disease Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians EvidenceBased Clinical Practice Guidelines // Chest. 2012. Vol. 141, suppl. 2. Р. e419S-e494S. doi:10.1378/chest.11-2301

[31] Boutitie F, Pinede L, Schulman S, et al. Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants' data from seven trials. BMJ. 2011;342:d3036. doi:10.1136/bmj.d3036

[32] Agnelli G., Becattini C. Risk assessment for recur-rence and optimal agents for extended treatment of venous thromboembolism // Hematology. 2013. Vol. 2013, №1. Р. 471-477. doi:10.1182/ashedu-cation-2013.1.471

[33] Kearon C, Akl EА, Comerota AJ, et al. Antithrombotic Therapy for VTE Disease Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141 (2 suppl):e419S-94S. doi:10.1378/chest.11-2301

[34] Dentali F., Sironi A.P., Ageno W., et al. Non O blood type is the commonest genetic risk factor for VTE: results from a metaanalysis of the literature // Seminars in Thrombosis and Hemostasis. 2012. Vol. 38, №5. Р. 535-548. doi:10.1055/s-0032-1315758

[35] Agnelli G, Becattini C. Risk assessment for recurrence and optimal agents for extended treatment of venous thromboembolism. Hematology. 2013;2013 (1):471-7. doi:10.1182/asheducation-2013.1.471

[36] Landefeld C.S., Beyth R.J. Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention // The American Journal of Medicine. 1993. Vol. 95, №3. Р. 315-328. doi:10.1016/0002-9343(93)90285-w

[37] Dentali F, Sironi AP, Ageno W, et al. Non-O blood type is the commonest genetic risk factor for VTE: results from a meta-analysis of the literature. Seminars in Thrombosis and Hemostasis. 2012;38(5): 535-48. doi:10.1055/s-0032-1315758

[38] Heit J.A. Predicting the Risk of Venous Thromboembolism Recurrence // American Journal of Hematology. 2012. Vol. 87, Suppl. 1. Р. S63-S67. doi:10.1002/ajh.23128

[39] Landefeld CS, Beyth RJ. Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention. The American Journal of Medicine. 1993; 95(3):315-28. doi:10.1016/0002-9343(93)90285-w

[40] Sode B.F., Allin K.H., Dahl M., et al. Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type // CMAJ. 2013. Vol. 185, №5. Р. E229-E237. doi:10.1503/cmaj.121636

[41] Heit JA. Predicting the Risk of Venous Thrombo-embolism Recurrence. American Journal of Hematology. 2012;87(Suppl 1):S63-7. doi:10.1002/ajh.23128

[42] Kearon C., Kahn S.R., Agnelli G., et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians evidencebased clinical practice guidelines (8th edition) // Chest. 2008. Vol. 133, Suppl. 6. P. 454S-545S. doi:10.1378/chest.08-0658

[43] Sode BF, Allin KH, Dahl M, et al. Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type. CMAJ. 2013;185(5):E229-37. doi:10.1503/cmaj.121636

[44] Kim K., Yamashita Y., Morimoto T., et al. Risk Factors for Major Bleeding during Prolonged Anticoagulation Therapy in Patients with Venous Thromboembolism: From the COMMAND VTE Registry // Thrombosis and Haemostasis. 2019. Vol. 119, №9. Р. 1498-1507. doi:10.1055/s-0039-1692425

[45] Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133(Suppl 6):454S-545S. doi:10.1378/chest.08-0658

[46] Kaatz S., Qureshi W., Fain C., et al. Duration of anticoagulation treatment in patients with venous thromboembolism // The Journal of the American Osteopathic Association. 2010. Vol. 110, №11. Р. 638-644.

[47] Kim K, Yamashita Y, Morimoto T, et al. Risk Factors for Major Bleeding during Prolonged Anticoagulation Therapy in Patients with Venous Thromboembolism: From the COMMAND VTE Registry. Thrombosis and Haemostasis. 2019;119(9):1498-507. doi:10.1055/s-0039-1692425

[48] Eichinger S., Heinze G., Jandeck L.M., et al. Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model // Circulation. 2010. Vol. 121, №14. Р. 1630-1636. doi:10.1161/CIRCULATIONAHA.109.925214

[49] Kaatz S, Qureshi W, Fain C, et al. Duration of anti-coagulation treatment in patients with venous thromboembolism. The Journal of the American Osteopathic Association. 2010;110(11):638-44.

[50] Rodger M.A., Kahn S.R., Wells P.S., et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy // CMAJ. 2008. Vol. 179, №5. Р. 417-426. doi:10.1503/cmaj.080493

[51] Eichinger S, Heinze G, Jandeck LM, et al. Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation. 2010;121(14):1630-6. doi:10.1161/CIRCULATIONAHA.109.925214

[52] Tosetto A., Iorio A., Marcucci M., et al. Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH) // Journal of Thrombosis and Haemostasis. 2012. Vol. 10, №6. Р. 1019-1025. doi:10.1111/j.1538-7836.2012.04735.x

[53] Rodger MA, Kahn SR, Wells PS, et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ. 2008;179(5):417-26. doi:10.1503/cmaj.080493

[54] Louzada M.L., Carrier M., LazoLangner A., et al. Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancerassociated venous thromboembolism // Circulation. 2012. Vol. 126, №4. Р. 448-454. doi:10.1161/CIRCULATIONAHA.111.051920

[55] Tosetto A, Iorio A, Marcucci M, et al. Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). Journal of Thrombosis and Haemostasis. 2012;10(6):1019-25. doi:10.1111/j.1538-7836.2012.04735.x

[56] Rodger M.A., Le Gal G., Anderson D.R., et al. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study // BMJ. 2017. Vol. 356. Р. j1065. doi:10.1136/bmj.j1065

[57] Louzada ML, Carrier M, Lazo-Langner A, et al. Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism. Circulation. 2012;126(4):448-54. doi: 10.1161/CIRCULATIONAHA.111.051920

[58] Кириенко А.И., Панченко Е.П., Андрияшкин В.В. Венозный тромбоз в практике терапевта и хирурга. М.: Планида; 2012.

[59] Rodger MA, Le Gal. G, Anderson DR, et al. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study. BMJ. 2017;356:j1065. doi:10.1136/bmj.j1065

[60] Schulman S., Kearon C., Kakkar A.K., et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism // The New England Journal of Medicine. 2013. Vol. 368, №8. Р. 709-718. doi:10.1056/NEJMoa1113697

[61] Kiriyenko AI, Panchenko EP, Andriyashkin VV. Venoznyy tromboz v praktike terapevta i khirurga. Moscow: Planida; 2012. (In Russ).

[62] Bauersachs R., Berkowitz S.D., Brenner B., et al. Oral rivaroxaban for symptomatic venous thromboembolism // The New England Journal of Medicine. 2010. Vol. 363, №26. Р. 2499-2510. doi:10.1056/NEJMoa1007903

[63] Schulman S, Kearon C, Kakkar AK, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. The New England Journal of Medicine. 2013;368(8):709-18. doi:10.1056/NEJMoa1113697

[64] Marcucci M., Iorio A., Douketis J.D., et al. Risk of recurrence after a first unprovoked venous thromboembolism: external validation of the Vienna Prediction Model with pooled individual patient data // Journal of Thrombosis and Haemostasis. 2015. Vol. 13, №5. Р. 775-781. doi:10.1111/jth.12871

[65] auersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. The New England Journal of Medicine. 2010; 363(26):2499-510. doi:10.1056/NEJMoa1007903

[66] Jiang Q.J., Bai J., Jin J., et al. Sulodexide for Secondary Prevention of Recurrent Venous Thromboembolism: A Systematic Review and Meta-Analysis // Frontiers in Pharmacology. 2018. №9. Р. 876. doi:10.3389/fphar.2018.00876.eCollection 2018

[67] Marcucci M, Iorio A, Douketis JD, et al. Risk of recurrence after a first unprovoked venous thromboembolism: external validation of the Vienna Prediction Model with pooled individual patient data. Journal of Thrombosis and Haemostasis. 2015; 13(5):775-81. doi:10.1111/jth.12871

[68] Петриков А.С., Дудин Д.В., Зайцев С.В., и др. Влияние продленной антитромботической терапии на развитие посттромботического синдрома у больных с проксимальным тромбозом глубоких вен нижних конечностей // Стационарозамещающие технологии: Амбулаторная хирургия. 2018. №3-4. С. 83-88. doi:10.21518/1995-1477-2018-3-4-83-88

[69] Jiang QJ, Bai J, Jin J, et al. Sulodexide for Secondary Prevention of Recurrent Venous Thromboembolism: A Systematic Review and Meta-Analysis. Frontiers in Pharmacology. 2018;(9):876. doi:10.3389/fphar.2018.00876.eCollection 2018

[70] Петриков А.С., Дудин Д.В., Валова О.В., др. Возможности длительной антитромботической терапии у больных с проксимальным тромбозом глубоких вен нижних конечностей // Вестник СурГУ. Медицина. 2018. №2. С. 37-43.

[71] Petrikov AS, Dudin DV, Zaitsev SV, et al. The influence of prolonged antithrombotic therapy on the development of post-thrombotic syndrome in patients with proximal deep vein thrombosis of the lower limbs. Statsionarozameshchayushchiye Tekhnologii: Ambulatornaya Khirurgiya. 2018;(3-4):83-8. doi:10.21518/1995-1477-2018-3-4-83-88

[72] Agnelli G., Buller H.R., Cohen A., et al. Apixaban for extended treatment of venous thromboembolism // The New England Journal of Medicine. 2013. Vol. 368, №8. Р. 699-708. doi:10.1056/NEJMoa1207541

[73] Petricov AS, Dudin DV, Valova OV, et al. Possibilities of long-lasting anti-thrombotic therapy in patients with proximal thrombosis of lower limbs deep veins. Vestnik SurGU. Medicina. 2018;(2):37-43. (In Russ).

[74] Andreozzi G.M., Bignamini A.A., Davi G., et al. Sulodexide for the Prevention of Recurrent Venous Thromboembolism: the Sulodexide in Secondary Prevention of Recurrent Deep Vein Thrombosis (SURVET) Study: a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial // Circulation. 2015. Vol. 132, №20. Р. 1891-1897. doi:10.1161/CIRCULATIONAHA.115.016930

[75] Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. The New England Journal of Medicine. 2013;368 (8):699-708. doi:10.1056/NEJMoa1207541

[76] Brighton T.A., Eikelboom J.W., Mann K., et al. Low-dose aspirin for preventing recurrent venous thromboembolism // The New England Journal of Medicine. 2012. Vol. 367, №21. Р. 1979-1987. doi:10.1056/NEJMoa1210384

[77] Sulodexide for the Prevention of Recurrent Venous Thromboembolism: the Sulodexide in Secondary Prevention of Recurrent Deep Vein Thrombosis (SURVET) Study: a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Сirculation. 2015;132(20):1891-7. doi:10.1161/CIRCULATIONAHA.115.016930

[78] Büller H.R., Décousus H., Grosso M.A., et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism // The New England Journal of Medicine. 2013. Vol. 369, №15. Р. 1406-1415. doi:10.1056/NEJMoa1306638

[79] Brighton TA, Eikelboom JW, Mann K, et al. Low-dose aspirin for preventing recurrent venous thromboembolism. The New England Journal of Medicine. 2012;367(21):1979-87. doi:10.1056/NEJMoa1210384

[80] Kearon C., Gent M., Hirsh J., et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism // The New England Journal of Medicine. 1999. Vol. 340, №12. Р. 901-907. doi:10.1056/NEJM199903253401201

[81] Büller HR, Décousus H, Grosso MA, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. The New England Journal of Medicine. 2013;369(15):1406-15. doi:10.1056/NEJMoa1306638

[82] Ridker P.M., Goldhaber S.Z., Danielson E., et al. Longterm, lowintensity warfarin therapy for the prevention of recurrent venous thromboembolism // The New England Journal of Medicine. 2003. Vol. 348, №15. Р. 1425-1434. doi:10.1016/S1062-1458 (03)00259-9

[83] Kearon C, Gent M, Hirsh J, et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. The New England Journal of Medicine. 1999;340(12):901-7. doi:10.1056/NEJM 199903253401201

[84] Becattini C., Agnelli G., Schenone A., et al. Aspirin for preventing the recurrence of venous thrombo-embolism // The New England Journal of Medicine. 2012. Vol. 366, №21. Р. 1959-1967. doi:10.1056/NEJMoa1114238

[85] Ridker PM, Goldhaber SZ, Danielson E, et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. The New England Journal of Medicine. 2003;348 (15):1425-34. doi:10.1016/S1062-1458(03)00259-9

[86] Linkins L.A., Choi P.T., Douketis J.D. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a metaanalysis // Annals of Internal Medicine. 2003. Vol. 139, №11. Р. 893-900. doi:10.7326/0003-4819-139-11-200312020-00007

[87] Becattini C, Agnelli G, Schenone A, et al. Aspirin for preventing the recurrence of venous thrombo-embolism. The New England Journal of Medicine. 2012;366(21):1959-67. doi:10.1056/NEJMoa1114238

[88] Kearon C., Ginsberg J.S., Kovacs M.J., et al. Comparison of lowintensity warfarin therapy with conventionalintensity warfarin therapy for longterm prevention of recurrent venous thromboembolism // The New England Journal of Medicine. 2003. Vol. 349, №7. Р. 631-639. doi:10.1056/NEJMoa035422

[89] Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Annals of Internal Medicine. 2003;139 (11):893-900. doi:10.7326/0003-4819-139-11-200312020-00007

[90] Simes J., Becattini C., Agnelli G., et al. Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration // Circulation. 2014. Vol. 130, №13. Р. 1062-1071. doi:10.1161/CIRCULATIONAHA.114.008828

[91] Kearon C, Ginsberg JS, Kovacs MJ, et al. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. The New England Journal of Medicine. 2003;349(7): 631-9. doi:10.1056/NEJMoa035422

[92] Pompilio G., Integlia D., Raffetto J., et al. Comparaive Efficacy and Safety of Sulodexide and Other Extended Anticoagulation Treatments for Prevention of Recurrent Venous Thromboembolism: A Bayesian Network Metaanalysis // TH Open. 2020. Vol. 4, №2. Р. e80-e93. doi:10.1055/s-0040-1709731

[93] Simes J, Becattini C, Agnelli G, et al. Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration. Circulation. 2014; 130(13): 1062-71. doi:10.1161/CIRCULATIONAHA.114.008828

[94] Konstantinides S.V., Meyer G., Becattini C., et al. 2019 ESC Guidelines on the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS) // European Heart Journal. 2020. Vol. 41, №4. Р. 543-603. doi:10.1093/eurheartj/ehz405

[95] Pompilio G, Integlia D, Raffetto J, et al. Сomparaive Efficacy and Safety of Sulodexide and Other Extended Anticoagulation Treatments for Prevention of Recurrent Venous Thromboembolism: A Bayesian Network Meta-analysis. TH Open. 2020;4(2):e80-e93. doi:10.1055/s-0040-1709731

[96] Weitz J.I., Lensing A.W.A., Prins M.H., et al. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism // The New England Journal of Medicine. 2017. Vol. 376, №13. Р. 1211-1222. doi:10.1056/NEJMoa1700518

[97] Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines on the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). European Heart Journal. 2020;41(4): 543-603. doi:10.1093/eurheartj/ehz405

[98] Mai V., Bertoletti L., Cucherat M., et al. Extended anticoagulation for the secondary prevention of venous thromboembolic events: An updated network metaanalysis // PLoS One. 2019. Vol. 14, №4. Р. e0214134. doi:10.1371/journal.pone.0214134

[99] Weitz JI, Lensing AWA, Prins MH, et al. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism. The New England Journal of Medicine. 2017;376(13):1211-22. doi:10.1056/NEJMoa1700518

[100] Mai V, Bertoletti L, Cucherat M, et al. Extended anticoagulation for the secondary prevention of venous thromboembolic events: An updated network meta-analysis. PLoS One. 2019;14(4):e0214134. doi:10.1371/journal.pone.0214134

RIGHTS & PERMISSIONS

Eco-Vector