Effect of Direct Oral Anticoagulants for Ulcer Epithelization and Laser Doppler Flowmetry Parameters In Patients with Diabetic Foot Syndrome and Atrial Fibrillation

Aim. To study changes in epithelialization of diabetic foot ulcers and parameters of laser Doppler flowmetry (LDF) in patients with diabetic foot syndrome (DFS) and atrial fibrillation (AF) during complex therapy with the addition of direct oral anticoagulants (DOAC).

Material and methods. An open-label comparative randomized study in parallel groups was performed. Patients with neuroischemic DFS and persistent FA without previous anticoagulant therapy were randomized into two groups: combination therapy for DFS and rivaroxaban (group 1; n=24) or combination therapy for DFS and dabigatran (group 2; n=22). Changes in local status in diabetic foot ulcers, coagulogram parameters and LDF were studied at 4 and 12 weeks.

Results. Complete epithelialization of diabetic foot ulcers after 12 weeks was found in 14 (58.3%) patients in group 1, and in 10 (45.4%) patients in group 2. Statistically significant improvements in LDF parameters were found in both groups in both groups: an increase in the microcirculation index by 53.5% (p=0.02), pulse wave by 124.0% (p=0.003), respiratory wave by 59.4% (p=0.007) was found in group 1. An increase in the microcirculation index by 48.5% (p=0.02), pulse wave by 73.1% (p=0.003), respiratory wave by 47.1% (p=0.03) were found in group 2.

Conclusion. Positive statistically significant changes in epithelialization of diabetic foot ulcers and LDF parameters were found in patients with DFS and AF during 12 weeks of complex therapy with the addition of DOACs (rivaroxaban and dabigatran). Further research for DOACs in DFS patients is needed.

1. Fabrichnova AA, Kulikov DA, Misnikova IV, et al. Hemorheological alterations in diabetes mellitus. Endocrinology. News. Opinions. Education. 2018;7(2)26-34 (In Russ.). DOI:10.24411/2304-95292018-12002.

2. Balabolkin, MI, Klebanova EM, Kreminskaya VM. Pathogenesis and mechanisms of development of angiopathies in diabetes mellitus. Cardiology. 2000;40(10):74-87. (In Russ.)

3. Dеvеhat CLe, Vimeux M, Khodabandehlou T. Blood rheology in patients with diabetes mellitus. Clin Hemorheol Microcirc. 2004;30(3-4):297-300.

4. Firsov NN, Korotaeva TV, Klimova NV, et al. Dependence analysis of peripheral blood flow from microrheological blood properties. Regional Blood Circulation and Microcirculation. 2010;9(4):58-62 (In Russ.). DOI:10.24884/1682-6655-2010-9-4-58-62.

5. Cho YI, Mooney MP, Cho DJ. Hemorheological disorders in diabetes mellitus. J Diabetes Sci Technol. 2006;2(6)24-28. DOI:10.1177/193229680800200622

6. Costa G, Gonçalves L, Teixeira R. The efficacy and safety of direct oral anticoagulants plus aspirin in symptomatic lower extremity peripheral arterial disease: a systematic review and meta-analysis of randomized controlled trials. J Thromb Thrombolysis. 2021 Mar 11. DOI:10.1007/s11239-02102417-3.

7. Barkhatova NA. Dynamics of tissue perfusion after indirect limb revascularization and angitropic therapy in diabetic foot syndrome. Bulletin of the Council of Young Scientists and Specialists of Chelyabinsk Region. 2017;3(18):15-8 (In Russ.)

8. Kudritsky SYu. Effect of cryoplasmapheresis on microcirculation in patients with diabetic foot syndrome. Modern technologies in medicine. 2010;3:84-6 (In Russ.)

9. Stepanova AP, Karonov TL, Galagudza MM. Microcirculation indices in patients with type II diabetes mellitus with diabetic peripheral neuropathy during therapy with various doses of D vitamin. Regional Blood Circulation and Microcirculation. 2019;18(4):19-28 (In Russ.). DOI:10.24884/16826655-2019-18-4-19-28.

10. Levin GYa, Kudritsky SYu, Izumrudov MR. Correlation of changes in hemorheology and microcirculation in diabetic foot syndrome. Regional Blood Circulation and Microcirculation. 2011;10(39):44-8 (In Russ.). DOI:10.24884/1682-6655-2011-10-3-44-48.

11. Krupatkin AI, Sidorov VV. Laser Doppler flowmetry of blood microcirculation. Moscow: Medicina; 2005 (In Russ.).

12. Balabolkin MI, Mamayeva GG, Troshina EA. Use of a laser Doppler flowmeter for early diagnosis of diabetic microangiopathies. Problems of Endocrinology. 1994;40(6):19-20. (In Russ.). DOI: 10.14341/probl12185.

13. Keast DH, Bowering K, Evans AW, et al. MEASURE assessment framework for developing best practice recommendations for wound assessment. Wound Rep Reg. 2004;12(3):1-17. DOI:10.1111/j.1067-1927.2004.0123S1.x

14. Kuzmina TN, Rogova NV, Khokhlova IV, et al. Features of Microcirculation in the Lower Extremities on the Background of Diabetic Foot Syndrome. Difficult Patient. 2020;3(18)38-40 (In Russ.). DOI:10.24411/2074-1995-2020-10018.

15. Sheehan P, Jones P, Casselli A, et al. Percent change in wound area of diabetic foot ulcers over a 4week period is a r obust predictor of complete healing in a 12-week prospective trial. Diabetes Care. 2003;26(6):1879-82. DOI:10.2337/diacare.26.6.1879.

16. Antovich J, Kondrat’eva TB. Control methods of therapy with direct oral anticoagulants: the state of the problem. Clinical Medicine. 2018;96(2):101-5. (In Russ.). DOI:10.18821/0023-2149-2018-96-2-101105.

17. Al-Aieshy F, Malmstrom RE, Antovic J, et al. Clinical evaluation of laboratory methods to monitor exposure of rivaroxaban at through and peak in patients with atrial fibrillation. Eur J Clin Pharmacol. 2016;72(6):671-9. DOI:10.1007/s00228-016-2060-y.

18. Douxfils J, Mullier F, Robert S, et.al. Impact of Dabigatran on a large panel of routine or specific coagulation assays. Laboratory recommendations for monitoring of Dabigatran etexilate. Thromb Haemost. 2012;107(5):985-97. DOI:10.1160/TH11-11-0804.