Effectiveness and Safety of Direct Oral Anticoagulants Compared to Warfarin in Treatment Naïve Non-valvular Atrial Fibrillation Patients in the US Department of Defense Population

Overview

Journal BMC Cardiovasc Disord

Publisher Biomed Central

Specialty Cardiology & Vascular Diseases

Date 2019 Jun 15

PMID 31195999

Citations 16

Authors

Kiran Gupta

Jeffrey Trocio

Allison Keshishian

Qisu Zhang

Oluwaseyi Dina

Jack Mardekian

Anagha Nadkarni

Thomas C Shank

Affiliations

Soon will be listed here.

Abstract

Background: Clinical trials have demonstrated that direct oral anticoagulants (DOACs) are at least non-inferior to warfarin in reducing the risk of stroke/systemic embolism (SE) among patients with non-valvular atrial fibrillation (NVAF), but the comparative risk of major bleeding varies between DOACs and warfarin. Using US Department of Defense (DOD) data, this study compared the risk of stroke/SE and major bleeding for DOACs relative to warfarin.

Methods: Adult patients with ≥1 pharmacy claim for apixaban, dabigatran, rivaroxaban, or warfarin from 01 Jan 2013-30 Sep 2015 were selected. Patients were required to have ≥1 medical claim for atrial fibrillation during the 12-month baseline period. Patients with a warfarin or DOAC claim during the 12-month baseline period were excluded. Each DOAC cohort was matched to the warfarin cohort using propensity score matching (PSM). Cox proportional hazards models were conducted to evaluate the risk of stroke/SE and major bleeding of each DOAC vs warfarin.

Results: Of 41,001 identified patients, there were 3691 dabigatran-warfarin, 8226 rivaroxaban-warfarin, and 7607 apixaban-warfarin matched patient pairs. Apixaban was the only DOAC found to be associated with a significantly lower risk of stroke/SE (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.39, 0.77; p < 0.001) and major bleeding (HR: 0.65; 95% CI: 0.53, 0.80; p < 0.001) compared to warfarin. Dabigatran and rivaroxaban initiation were associated with similar risk of stroke/SE (dabigatran: HR: 0.68; 95% CI: 0.43, 1.07; p = 0.096; rivaroxaban: HR: 0.83; 95% CI: 0.64, 1.09; p = 0.187) and major bleeding (dabigatran: HR: 1.05; 95% CI: 0.79, 1.40; p = 0.730; rivaroxaban: HR: 1.07; 95% CI: 0.91, 1.27; p = 0.423) compared to warfarin.

Conclusion: Among NVAF patients in the US DOD population, apixaban was associated with significantly lower risk of stroke/SE and major bleeding compared to warfarin. Dabigatran and rivaroxaban were associated with similar risk of stroke/SE and major bleeding compared to warfarin.

Citing Articles

Non-Medical Switching or Discontinuation Patterns among Patients with Non-Valvular Atrial Fibrillation Treated with Direct Oral Anticoagulants in the United States: A Claims-Based Analysis.

Ingham M, Romdhani H, Patel A, Ashton V, Caron-Lapointe G, Tardif-Samson A J Mark Access Health Policy. 2024; 12(3):252-263.

PMID: 39315122 PMC: 11417902. DOI: 10.3390/jmahp12030020.

Efficacy and Safety of Direct Oral Anticoagulants Versus Warfarin in Saudi Patients With Atrial Fibrillation.

Almegren M Cureus. 2024; 16(4):e58886.

PMID: 38800246 PMC: 11116736. DOI: 10.7759/cureus.58886.

Distinct pleiotropic effects of direct oral anticoagulants on cultured endothelial cells: a comprehensive review.

Atzemian N, Kareli D, Ragia G, Manolopoulos V Front Pharmacol. 2023; 14:1244098.

PMID: 37841935 PMC: 10576449. DOI: 10.3389/fphar.2023.1244098.

Risk Profiles of New Users of Oral Anticoagulants Between 2011 and 2019 in Germany.

Voss A, Kollhorst B, Platzbecker K, Amann U, Haug U Clin Epidemiol. 2023; 15:827-837.

PMID: 37483262 PMC: 10362862. DOI: 10.2147/CLEP.S405585.

Clinical outcomes in patients with atrial fibrillation treated with DOACs in a specialized anticoagulation center: Critical appraisal of real-world data.

Moret C, Acosta-Isaac R, Mojal S, Corrochano M, Jimenez B, Plaza M PLoS One. 2023; 18(2):e0279297.

PMID: 36827286 PMC: 9955586. DOI: 10.1371/journal.pone.0279297.

References

Austin P . Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009; 28(25):3083-107. PMC: 3472075. DOI: 10.1002/sim.3697. View

Austin P . The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat Med. 2013; 33(7):1242-58. PMC: 4285179. DOI: 10.1002/sim.5984. View

Pisters R, Lane D, Nieuwlaat R, de Vos C, Crijns H, Lip G . A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010; 138(5):1093-100. DOI: 10.1378/chest.10-0134. View

Thigpen J, Dillon C, Forster K, Henault L, Quinn E, Tripodis Y . Validity of international classification of disease codes to identify ischemic stroke and intracranial hemorrhage among individuals with associated diagnosis of atrial fibrillation. Circ Cardiovasc Qual Outcomes. 2015; 8(1):8-14. PMC: 4654947. DOI: 10.1161/CIRCOUTCOMES.113.000371. View

McCaffrey D, Griffin B, Almirall D, Slaughter M, Ramchand R, Burgette L . A tutorial on propensity score estimation for multiple treatments using generalized boosted models. Stat Med. 2013; 32(19):3388-414. PMC: 3710547. DOI: 10.1002/sim.5753. View

Colilla S, Crow A, Petkun W, Singer D, Simon T, Liu X . Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population. Am J Cardiol. 2013; 112(8):1142-7. DOI: 10.1016/j.amjcard.2013.05.063. View

Amin A, Keshishian A, Trocio J, Dina O, Le H, Rosenblatt L . Risk of stroke/systemic embolism, major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran or rivaroxaban compared with warfarin in the United States Medicare population. Curr Med Res Opin. 2017; 33(9):1595-1604. DOI: 10.1080/03007995.2017.1345729. View

Mancusi A, Ruggeri L, Velardi A . Haploidentical hematopoietic transplantation for the cure of leukemia: from its biology to clinical translation. Blood. 2016; 128(23):2616-2623. DOI: 10.1182/blood-2016-07-730564. View

Patel M, Mahaffey K, Garg J, Pan G, Singer D, Hacke W . Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011; 365(10):883-91. DOI: 10.1056/NEJMoa1009638. View

10.

Yao X, Abraham N, Sangaralingham L, Bellolio M, McBane R, Shah N . Effectiveness and Safety of Dabigatran, Rivaroxaban, and Apixaban Versus Warfarin in Nonvalvular Atrial Fibrillation. J Am Heart Assoc. 2016; 5(6). PMC: 4937291. DOI: 10.1161/JAHA.116.003725. View

11.

Ntaios G, Papavasileiou V, Makaritsis K, Vemmos K, Michel P, Lip G . Real-World Setting Comparison of Nonvitamin-K Antagonist Oral Anticoagulants Versus Vitamin-K Antagonists for Stroke Prevention in Atrial Fibrillation: A Systematic Review and Meta-Analysis. Stroke. 2017; 48(9):2494-2503. DOI: 10.1161/STROKEAHA.117.017549. View

12.

Deitelzweig S, Farmer C, Luo X, Vo L, Li X, Hamilton M . Risk of major bleeding in patients with non-valvular atrial fibrillation treated with oral anticoagulants: a systematic review of real-world observational studies. Curr Med Res Opin. 2017; 33(9):1583-1594. DOI: 10.1080/03007995.2017.1347090. View

13.

Berger M, Mamdani M, Atkins D, Johnson M . Good research practices for comparative effectiveness research: defining, reporting and interpreting nonrandomized studies of treatment effects using secondary data sources: the ISPOR Good Research Practices for Retrospective Database Analysis Task.... Value Health. 2009; 12(8):1044-52. DOI: 10.1111/j.1524-4733.2009.00600.x. View

14.

Villines T, Schnee J, Fraeman K, Siu K, Reynolds M, Collins J . A comparison of the safety and effectiveness of dabigatran and warfarin in non-valvular atrial fibrillation patients in a large healthcare system. Thromb Haemost. 2015; 114(6):1290-8. DOI: 10.1160/TH15-06-0453. View

15.

Tamayo S, Peacock W, Patel M, Sicignano N, Hopf K, Fields L . Characterizing major bleeding in patients with nonvalvular atrial fibrillation: a pharmacovigilance study of 27 467 patients taking rivaroxaban. Clin Cardiol. 2015; 38(2):63-8. PMC: 6685471. DOI: 10.1002/clc.22373. View

16.

Li X, Deitelzweig S, Keshishian A, Hamilton M, Horblyuk R, Gupta K . Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in "real-world" clinical practice. A propensity-matched analysis of 76,940 patients. Thromb Haemost. 2017; 117(6):1072-1082. PMC: 6291856. DOI: 10.1160/TH17-01-0068. View

17.

Hart R, Pearce L, Aguilar M . Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007; 146(12):857-67. DOI: 10.7326/0003-4819-146-12-200706190-00007. View

18.

January C, Samuel Wann L, Alpert J, Calkins H, Cigarroa J, Cleveland Jr J . 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014; 130(23):2071-104. DOI: 10.1161/CIR.0000000000000040. View

19.

Granger C, Alexander J, McMurray J, Lopes R, Hylek E, Hanna M . Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011; 365(11):981-92. DOI: 10.1056/NEJMoa1107039. View

20.

Carmo J, Costa F, Ferreira J, Mendes M . Dabigatran in real-world atrial fibrillation. Meta-analysis of observational comparison studies with vitamin K antagonists. Thromb Haemost. 2016; 116(4):754-63. DOI: 10.1160/TH16-03-0203. View