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CC BY 4.0 · TH Open 2023; 07(01): e82-e93
DOI: 10.1055/a-2013-3346
Original Article

Effectiveness and Safety of Rivaroxaban Versus Warfarin among Nonvalvular Atrial Fibrillation Patients with Concomitant Obstructive Sleep Apnea

Nitesh Sood
1   Arrhythmia Services, Southcoast Health, Massachusetts, United States
,
Veronica Ashton
2   Real World Value and Evidence, Janssen Scientific Affairs LLC, Titusville, New Jersey, United States
,
Youssef Bessada
3   University of Connecticut School of Pharmacy, Connecticut, United States
,
Katelyn Galli
3   University of Connecticut School of Pharmacy, Connecticut, United States
,
Brahim K. Bookhart
2   Real World Value and Evidence, Janssen Scientific Affairs LLC, Titusville, New Jersey, United States
,
Craig I. Coleman 
3   University of Connecticut School of Pharmacy, Connecticut, United States
4   Evidence-Based Practice Center, Hartford Hospital, Hartford, Connecticut, United States
› Author Affiliations Funding This study was supported by funding from Janssen Scientific Affairs, LLC, Titusville, NJ, United States.
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Abstract

Background Obstructive sleep apnea (OSA) is associated with an increased incidence of atrial fibrillation (AF), hypertension, diabetes, heart failure, coronary heart disease, stroke, and death. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular AF (NVAF) patients with concomitant OSA.

Methods This was an analysis of electronic health record (EHR) data from November 2010 to December 2021. We included adults with NVAF and OSA at baseline, newly initiated on rivaroxaban or warfarin, and with ≥12 months of prior EHR activity. Patients with valvular disease, alternative indications for oral anticoagulation, or who were pregnant were excluded. The incidence rates of developing stroke or systemic embolism (SSE) and bleeding-related hospitalization were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using propensity score-overlap weighted proportional hazards regression. Multiple sensitivity and subgroup analyses were performed.

Results We included 21,940 rivaroxaban (20.1% at the 15 mg dose) and 38,213 warfarin (time-in-therapeutic range = 47.3 ± 28.3%) patients. Rivaroxaban was found to have similar hazard of SSE compared to warfarin (HR = 0.92, 95% CI = 0.82–1.03). Rivaroxaban was associated with a reduced rate of bleeding-related hospitalizations (HR = 0.85, 95% CI = 0.78–0.92) versus warfarin, as well as reductions in intracranial (HR = 0.76, 95% CI = 0.62–0.94) and extracranial (HR = 0.89, 95%CI = 0.81–0.97) bleeding. Upon sensitivity analysis restricting the population to men with a CHA2DS2VASc score ≥2 or women with a score ≥3, rivaroxaban was associated with a significant 33% risk reduction in SSE and 43% reduction in the risk of bleeding-related hospitalization. No significant interaction for the SSE or bleeding-related hospitalization outcomes was observed upon subgroup analyses.

Conclusion Among patients with NVAF and OSA, rivaroxaban had similar SSE risk versus warfarin but was associated with reductions in any intracranial and extracranial bleeding-related hospitalizations. Rivaroxaban was associated with significant reductions in SSE and bleeding-related hospitalizations when the study population was restricted to patients with a moderate-to-high risk of SSE. These data should provide prescribers with additional confidence in selecting rivaroxaban in NVAF patients who have OSA at the time of anticoagulation initiation.

Keywords

rivaroxaban - warfarin - sleep Apnea, obstructive - atrial fibrillation - observational studies


Publication History

Received: 19 December 2022

Accepted: 10 January 2023

Accepted Manuscript online:
14 January 2023

Article published online:
29 March 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 January CT, Wann LS, Calkins H. et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS Guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74 (01) 104-132
    CrossrefPubMedGoogle Scholar
  • 2 Gottlieb DJ, Punjabi NM. Diagnosis and management of obstructive sleep apnea: a review. JAMA 2020; 323 (14) 1389-1400
    CrossrefPubMedGoogle Scholar
  • 3 Goes CM, Falcochio PPNF, Drager LF. Strategies to manage obstructive sleep apnea to decrease the burden of atrial fibrillation. Expert Rev Cardiovasc Ther 2018; 16 (10) 707-713
    CrossrefPubMedGoogle Scholar
  • 4 Linz D, McEvoy RD, Cowie MR. et al. Associations of obstructive sleep apnea with atrial fibrillation and continuous positive airway pressure treatment: a review. JAMA Cardiol 2018; 3 (06) 532-540
    CrossrefPubMedGoogle Scholar
  • 5 May AM, Van Wagoner DR, Mehra R. OSA and cardiac arrhythmogenesis: mechanistic insights. Chest 2017; 151 (01) 225-241
    CrossrefPubMedGoogle Scholar
  • 6 Ng CY, Liu T, Shehata M, Stevens S, Chugh SS, Wang X. Meta-analysis of obstructive sleep apnea as predictor of atrial fibrillation recurrence after catheter ablation. Am J Cardiol 2011; 108 (01) 47-51
    CrossrefPubMedGoogle Scholar
  • 7 Monahan K, Brewster J, Wang L. et al. Relation of the severity of obstructive sleep apnea in response to anti-arrhythmic drugs in patients with atrial fibrillation or atrial flutter. Am J Cardiol 2012; 110 (03) 369-372
    CrossrefPubMedGoogle Scholar
  • 8 Yaranov DM, Smyrlis A, Usatii N. et al. Effect of obstructive sleep apnea on frequency of stroke in patients with atrial fibrillation. Am J Cardiol 2015; 115 (04) 461-465
    CrossrefPubMedGoogle Scholar
  • 9 Pengo MF, Faini A, Grote L. et al; ESADA Working Group. Impact of sleep apnea on cardioembolic risk in patients with atrial fibrillation: data from the ESADA Cohort. Stroke 2021; 52 (02) 712-715
    CrossrefPubMedGoogle Scholar
  • 10 Holmqvist F, Guan N, Zhu Z. et al; ORBIT-AF Investigators. Impact of obstructive sleep apnea and continuous positive airway pressure therapy on outcomes in patients with atrial fibrillation—results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). Am Heart J 2015; 169 (05) 647-654.e2
    CrossrefPubMedGoogle Scholar
  • 11 Koch H, Carlson N, Jakobsen C. et al. Sleep apnea and risk of ischemic stroke in patients with atrial fibrillation. Eur Heart J 2016; 37 (Suppl. 01) 302-303
    PubMedGoogle Scholar
  • 12 Imano H, Kato R, Tanikawa S. et al. Factor Xa inhibition by rivaroxaban attenuates cardiac remodeling due to intermittent hypoxia. J Pharmacol Sci 2018; 137 (03) 274-282
    CrossrefPubMedGoogle Scholar
  • 13 Optum® de-identified Electronic Health Record dataset (2007–2021).
    PubMed
  • 14 Keenan BT, Kirchner HL, Veatch OJ. et al. Multisite validation of a simple electronic health record algorithm for identifying diagnosed obstructive sleep apnea. J Clin Sleep Med 2020; 16 (02) 175-183
    CrossrefPubMedGoogle Scholar
  • 15 Laratta CR, Tsai WH, Wick J, Pendharkar SR, Johannson KA, Ronksley PE. Validity of administrative data for identification of obstructive sleep apnea. J Sleep Res 2017; 26 (02) 132-138
    CrossrefPubMedGoogle Scholar
  • 16 Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res 2011; 46 (03) 399-424
    CrossrefPubMedGoogle Scholar
  • 17 Centers for Medicare and Medicaid Services. Chronic conditions data warehouse. Accessed October 29, 2022, at: https://www2.ccwdata.org/web/guest/home
    PubMedGoogle Scholar
  • 18 Elixhauser A, Steiner C, Harris DR, Coffey RM. Comorbidity measures for use with administrative data. Med Care 1998; 36 (01) 8-27
    CrossrefPubMedGoogle Scholar
  • 19 Quan H, Li B, Couris CM. et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol 2011; 173 (06) 676-682
    Google Scholar
  • 20 Gilbert T, Neuburger J, Kraindler J. et al. Development and validation of a Hospital Frailty Risk Score focusing on older people in acute care settings using electronic hospital records: an observational study. Lancet 2018; 391 (10132): 1775-1782
    CrossrefPubMedGoogle Scholar
  • 21 Sterne JA, White IR, Carlin JB. et al. Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. BMJ 2009; 338: b2393
    CrossrefPubMedGoogle Scholar
  • 22 Thomas LE, Li F, Pencina MJ. Overlap weighting: a propensity score method that mimics attributes of a randomized clinical trial. JAMA 2020; 323 (23) 2417-2418
    CrossrefPubMedGoogle Scholar
  • 23 Centers for Medicare and Medicaid Services. General Equivalence Mappings. Accessed October 29, 2022 at: https://www.cms.gov/medicare/coding/icd10/downloads/icd-10_gem_fact_sheet.pdf
    PubMedGoogle Scholar
  • 24 Cunningham A, Stein CM, Chung CP, Daugherty JR, Smalley WE, Ray WA. An automated database case definition for serious bleeding related to oral anticoagulant use. Pharmacoepidemiol Drug Saf 2011; 20 (06) 560-566
    CrossrefPubMedGoogle Scholar
  • 25 Langan SM, Schmidt SA, Wing K. et al. The reporting of studies conducted using observational routinely collected health data statement for pharmacoepidemiology (RECORD-PE). BMJ 2018; 363: k3532
    CrossrefPubMedGoogle Scholar
  • 26 Patel MR, Mahaffey KW, Garg J. et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10) 883-891
    Google Scholar
  • 27 Szymanski FM, Lip GY, Filipiak KJ, Platek AE, Karpinski G. Usefulness of the SAME-TT2R2 score to predict anticoagulation control on VKA in patients with atrial fibrillation and obstructive sleep apnea. Int J Cardiol 2016; 204: 200-205
    CrossrefPubMedGoogle Scholar
  • 28 Coleman CI, Costa OS, Brescia CW, Vardar B, Abdelgawwad K, Sood N. Thromboembolism, bleeding and vascular death in nonvalvular atrial fibrillation patients with type 2 diabetes receiving rivaroxaban or warfarin. Cardiovasc Diabetol 2021; 20 (01) 52
    CrossrefPubMedGoogle Scholar
  • 29 Deitelzweig S, Keshishian A, Kang A. et al. Effectiveness and safety of oral anticoagulants among NVAF patients with obesity: insights from the ARISTOPHANES Study. J Clin Med 2020; 9 (06) 1633
    CrossrefPubMedGoogle Scholar
  • 30 Hindricks G, Potpara T, Dagres N. et al; ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42 (05) 373-498
    Google Scholar
  • 31 Mandereau-Bruno L, Léger D, Delmas MC. Obstructive sleep apnea: a sharp increase in the prevalence of patients treated with nasal CPAP over the last decade in France. PLoS One 2021; 16 (01) e0245392
    CrossrefPubMedGoogle Scholar
  • 32 Lyons MM, Bhatt NY, Pack AI, Magalang UJ. Global burden of sleep-disordered breathing and its implications. Respirology 2020; 25 (07) 690-702
    CrossrefPubMedGoogle Scholar
  • 33 Ramar K, Dort LC, Katz SG. et al. Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015. J Clin Sleep Med 2015; 11 (07) 773-827
    CrossrefPubMedGoogle Scholar
  • 34 Baker WL, Cios DA, Sander SD, Coleman CI. Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States. J Manag Care Pharm 2009; 15 (03) 244-252
    PubMedGoogle Scholar