Serdar GÜNAYDIN, Ali Baran BUDAK, Eren GÜNERTEM, Naim Boran TÜMER, Atike TEKELİ KUNT, Kanat ÖZIŞIK

Comparative efficacy of long-term anticoagulation in patients with iliofemoral acute deep vein thrombosis treated with pharmacomechanical catheter-directed thrombolysis

Aim: We aimed to compare the stability of pharmacologic profile, rate of symptomatic recurrent venous thromboembolism, major bleeding and the net clinical benefit on the regimen with vitamin K antagonist (VKA), low molecular weight heparin (LMWH) and direct oral anticoagulant (DOAC) for long-term anticoagulation in patients undergoing pharmaco-mechanical catheter-directed thrombolysis (PMCDT) for the treatment of deep vein thrombosis (DVT). Material and Methods: During the period from January 2019 until June 2019, data of 112 patients who underwent PMCDT for the treatment of acute iliofemoral DVT in our institution with long-term apixaban (Pfizer, Turkey) medication were prospectively collected (Group 1-DOAC). Data of control groups within January 2017- December 2018 period were collected retrospectively. Control groups consisted of PMCDT patients with extended LMWH (Tinzaparin, Abdi Ibrahim Pharma, Turkey) treatment (Group 2-LMWH; N=119) and with VKA (Coumadin, Eczacibasi Pharma, Turkey) treatment (Group 3- Control; N=111). Results: Patients treated with VKA showed a significant incompliance starting from third month up to one year. Patency rate diminished significantly below 70%. 32% of VKA patients were out of therapeutic range even in the first month leading to 40% at the end of the year. Likert Scale, Villalta/VCCS and VEINES-QOL-Sym scores confirmed the clinical data. Conclusion: This study highlights the potential role of DOAC as a reasonable alternative to VKAs/LMWH in the long-term anticoagulation strategy for DVT. We await larger clinical trials to support these findings and establish the role of DOAC as the standard of care for patients with DVT.

Farmakomekanik kateter aracılı tromboliz ile tedavi edilen akut ilyofemoral derin ven trombozlu hastalarda uzun süreli antikoagülasyonun karşılaştırmalı etkinliği

Amaç: Derin ven trombozu (DVT) tedavisi için farmakomekanik kateter aracılı trombliz (FMKAT) yapılan hastalarda; vitamin K antagonistlerini(VKA), düşük molekül ağırlıklı heparini (DMAH) ve direk oral antikoagülan ajanları (DOAK) farmakolojik profilllerinin stabilitesine, semptomatik rekürren venöz tromboembolik, major kanama ve klinik fayda oranlarına göre karşılaştırmayı hedefledik. Gereç ve Yöntemler: Ocak 2019 ile Haziran 2019 tarihleri arasında kliniğimizde akut iliofemoral DVT tanısı ile FMKAT yapılan ve uzun dönemde apiksaban (Pfizer, Türkiye) tedavisi ile takip edilen 112 hastanın verileri toplandı. (Grup 1- DOAK) Kontrol gruplarının dataları ise Ocak 2017 ile Aralık 2018 tarihleri arasında yine kliniğimizde akut iliofemoral DVT tanısı ile FMKAT yapılan ve uzun dönemde DMAH (Tinzaparin, Abdi Ibrahim İlaç, Türkiye) tedavisi (Group 2-DMAH; N=119) ve VKA(Coumadin, Eczacibasi İlaç, Türkiye) tedavisi (Grup 3- Kontrol N=111) hastalardan toplandı. Bulgular: VKA tedavisi ile takip edilen hastalarda 3.aydan başlayıp 1 yıla kadar ki takip sürelerinde belirgin oranda tedaviye uyumsuzluk saptandı. Patensi oranları %70'in altındaydı. VKA hastalarının %32'si yıl sonunda terapötik dozlarda değildi. Likert skalaları, Villalta/VCCS ve VEINES-QOL-Sym skorlama sistemlerinin sonuçları klinik sonuçlar ile uyumluydu. Sonuç: Bu çalışma DOAK'ların DVT hastalarında tedavi için DMAH ve VKA'lara uygun bir seçenek olduğunu gösterdi. DOAK tedavisinin DVT hastalarında standart bir tedavi olarak tercih edilebilmesi için bizim elde ettiğimiz sonuçları destekleyecek geniş kapsamlı klinik çalışmaların sonuçları beklenmektedir.

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1. Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol 2015; 8: 464-74

2. Streiff MB, Agnelli G, Connors JM et al. Guidance for the treatment of deep vein thrombosis and pulmonary embolism. J Thromb Thrombolysis 2016; 41: 32-67.

3. Ashrani AA, Heit JA. Incidence and cost burden of post-thrombotic syndrome. J Thromb Thrombolysis 2009; 28: 465–76.

4. Ridker PM, Goldhaber SZ, Danielson E et al. Long-term, lowintensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med. 2003; 348: 1425–34

5. Sobieraj DM, Coleman CI, Pasupuleti V, Deshpande A, Kaw R, Hernandez AV. Comparative efficacy and safety of anticoagulants and aspirin for extended treatment of venous thromboembolism: A network meta-analysis. Thromb Res 2015; 135: 888–96.

6. Schulman S, Kearon C, Kakkar AK et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013; 368: 709–18.

7. Einstein Investigators, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363: 2499–510.

8. Al Saleh AS, Berrigan P, Anderson D, Shivakumar S. Direct Oral Anticoagulants and Vitamin K Antagonists for Treatment of Deep Venous Thrombosis and Pulmonary Embolism in the Outpatient Setting: Comparative Economic Evaluation Can J Hosp Pharm 2017; 70: 188-99

9. Vedantham S, Goldhaber SZ, Kahn SR et al. Rationale and design of the ATTRACT Study: A multicenter randomized trial to evaluate pharmacomechanical catheter- directed thrombolysis for the prevention of postthrombotic syndrome in patients with proximal deep vein thrombosis. Am Heart J 2013; 165: 523-53

10. Wong PC, Chan YC, Law Y, Cheng SWK. Percutaneous mechanical thrombectomy in the treatment of acute iliofemoral deep vein thrombosis: a systematic review. Hong Kong Med J 2019; 25: 48-57.

11. Wells PS, Anderson DR, Bormanis J et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 1997; 350:1795–8.

12. Marder VJ, Soulen RL, Arichartakarn V et al. Quantitative venographic assessment of deep vein thrombosis in the evaluation of streptokinase and heparin therapy. J Lab Clin Med 1977; 89:1018–1029

13. Barrett JS, Gibiansky E, Hull RD, Planes A, Pentikis H, Hainer JW, Hua TA, Gastonguay M. Population pharmacodynamics in patients receiving tinzaparin for the prevention and treatment of deep vein thrombosis. Int J Clin Pharmacol Ther 2001; 39: 431-46.

14. Vedantham S, Grassi CJ, Ferral H et al. Reporting Standards for Endovascular Treatment of Lower Extremity Deep Vein Thrombosis. J Vasc Interv Radiol 2006; 17: 417–34

15. Lattimer CR, Kalodiki E, Azzam M, Geroulakos G. Validation of the Villalta Scale in Assessing Post-Thrombotic Syndrome Using Clinical, Duplex, and Hemodynamic Comparators. J Vasc Surg Venous Lymphat Disord 2014; 2: 8-14.

16. Meissner M, Natiello C, Nicholls S. Performance characteristics of the venous clinical severity score. J Vasc Surg 2002; 36: 889-95.

17. Lamping DL, Schroter S, Kurz X, Kahn SR, Abenhaim L. Evaluation of outcomes in chronic venous disorders of the leg: development of a scientifically rigorous, patient-reported measure of symptoms and quality of life. J Vasc Surg 2003; 37: 410–9.

18. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuunemann HJ. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141: 7–47 19. Field T (2019) Multicentre PROL, blinded-endpoint (PROBE) controlled trial of early anticoagulation with rivaroxaban versus standard of care in determining safety at 365 days in symptomatic cerebral venous thrombosis. NCT03178864 CgI.

20. Ferro JM, Coutinho JM, Dentali F et al. Safety and efficacy of dabigatran etexilate vs dose-adjusted warfarin in patients with cerebral venous thrombosis: a randomized clinical trial. JAMA Neurol 2019; 76: 1457–65

21. Lurkin A, Derex L, Fambrini A et al. Direct oral anticoagulants for the treatment of cerebral venous thrombosis. Cerebrovasc Dis 2019; 48: 32–7

22. Leow AS, Sia CH, Tan BY, Loh JP (2018) A meta-summary of case reports of non-vitamin K antagonist oral anticoagulant use in patients with left ventricular thrombus. J Thromb Thrombolysis 2018; 46: 68–73

23. Agnelli G, Buller HR, Cohen A et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369: 799–808.