Anticoagulant-related bleeding in patients with heart failure in combination with chronic obstructive pulmonary disease and atrial fibrillation. Experience with Idarucizumab

Aim. To study the characteristics of direct oral anticoagulant-related bleeding in patients with heart failure in combination with chronic obstructive pulmonary disease (COPD) and atrial fibrillation. To show the efficacy of idarucizumab in complex therapy of severe gastrointestinal bleeding caused by dabigatran.

Material and methods. The single-center prospective observational study included 150 patients with nonvalvular atrial fibrillation treated with direct oral anticoagulants. Of these patients, 75 had heart failure in combination with COPD (experimental group) and 75 — HF without comorbidities (comparison group). Groups were formed by propensity score matching. Sex, age, bleeding risk by HAS-BLED score were covariates. HF was diagnosed in accordance with the criteria applied by Russian Federal clinical guidelines. COPD was diagnosed according to GOLD 2011-2020 criteria. Frequency of all bleeding, major bleeding, bleeding into critical organs were evaluated. Follow-up period was 14 (12; 16) months. Cox regression method was used to determine relationships.

Results. Annual rate of major bleeding in group of HF and COPD was higher (Hazard ratio (HR) 3,0, 95% confidence interval (CI) 1,1-6,2, р=0,02), regardless of which anticoagulant was used. Gastrointestinal bleeding occurs in 7 (9,3%) and 2 (2,7%) patients (HR 3,5, 95% CI 1,1-7,3, р=0,05). In subjects with comorbidity, major and gastrointestinal bleeding were associated with partial pressure of arterial oxygen (HR 0,89, 95% CI 0,55-0,95 and HR 0,88, 95% CI 0,50-0,98 respectively), serum NT-pro-BNP (HR 1,10, 95% CI 1,05-2,14 and HR 1,14, 95% CI 0,07-4,28, respectively) and chemokine ligand 18 (HR 1,15, 95% CI 1,11-5,75 and HR 1,13, 95% CI 1,09-4,50). A case of successful use of idarucizumab for reversal of dabigatran anticoagulant effect in the patient with severe bleeding from esophageal erosion, nonvalvular AF, HF and COPD was reported. Coagulation was restored within 4 hours, which allowed to stop bleeding conservatively and antishock measures were effective.

Conclusion. Anticoagulation therapy in patients with AF and comorbidity of HF and COPD is associated with additional risk of major bleeding, especially gastrointestinal. Possibility to reverse the anticoagulant effect is an important argument when choosing an anticoagulant for these patients.

1. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007 Jun 19;146(12):857-67. doi:10.7326/0003-4819-146-12-200706190-00007.

2. Mitchell A, Watson MC, Welsh T, et al. Effectiveness and Safety of Direct Oral Anticoagulants versus Vitamin K Antagonists for People Aged 75 Years and over with Atrial Fibrillation: A Systematic Review and Meta-Analyses of Observational Studies. J Clin Med. 2019;8:E554. doi:10.3390/jcm8040554.

3. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51. doi:10.1056/NEJMoa0905561.

4. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-91. doi:10.1056/NEJMoa1009638.

5. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-92. doi:10.1056/NEJMoa1107039.

6. Packer M, Lam CSP, Lund LH, et al. Interdependence of Atrial Fibrillation and Heart Failure With a Preserved Ejection Fraction Reflects a Common Underlying Atrial and Ventricular Myopathy. Circulation. 2020;141(1):4-6. doi:10.1161/CIRCULATIONAHA.119.042996.

7. Carter P, Lagan J, Fortune C, et al. Association of Cardiovascular Disease With Respiratory Disease. J Am Coll Cardiol. 2019;73(17):2166-77. doi:10.1016/j.jacc.2018.11.063.

8. Rydberg DM, Linder M, Malmstrom RE, et al. Risk factors for severe bleeding events during warfarin treatment: the influence of sex, age, comorbidity and co-medication. Eur J Clin Pharmacol. 2020 Jun;76(6):867-876. doi:10.1007/s00228-020-02856-6. Epub 2020 Mar 28.

9. Pollack C, Reilly PA, van Ryn J, et al. Idarucizumab for Dabigatran Reversal — Full Cohort Analysis. N Engl J Med. 2017 Aug 3;377(5):431-41. doi:10.1056/NEJMoa1707278.

10. Mareev VYu, Fomin IV, Ageev FT, et al. Russian Heart Failure Society, Russian Society of Cardiology. Russian Scientific Medical Society of Internal Medicine Guidelines for Heart failure: chronic (CHF) and acute decompensated (ADHF). Diagnosis, prevention and treatment. Kardiologiia. 2018;58(S6):1-164. (In Russ.) doi:10.18087/cardio.2475.

11. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2020 report). Available at: https://goldcopd.org/wp-content/uploads/2019/12/GOLD-2020-FINAL-ver1.2-03Dec19_WMV.pdf (Дата обращения 06.04.2020).

12. 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 Consenathsus Decision Pways. J Am Coll Cardiol. 2017;70(24):3042-67 doi:10.1016/j.jacc.2017.09.1085.

13. Silverio A, Di Maio M, Prota C, et al. Safety and efficacy of non-vitamin K antagonist oral anticoagulants in elderly patients with atrial fibrillation. Eur Heart J Cardiovasc Pharmacother. 2019 Dec 12;pvz073. doi:10.1093/ehjcvp/pvz073.

14. Yee J, Kaide CG. Emergency Reversal of Anticoagulation. West J Emerg Med. 2019;20(5):770-83. doi:10.5811/westjem.2018.5.38235.