Ischemic stroke and systemic embolism among patients with non-valvular atrial fibrillation who abandon oral anticoagulant therapy

Abstract

Objectives

To compare the risk of stroke and systemic embolism (SE) among patients with nonvalvular atrial fibrillation (NVAF) who abandoned their first direct oral anticoagulant (DOAC) fill (“abandoners”) relative to patients who continued DOACs beyond the first fill (“continuers”).

Methods

In this retrospective longitudinal study, adults with NVAF prescribed DOACs were selected from Symphony Health, an ICON plc Company, PatientSource, 1 April 2017 to 31 October 2020. A 90-day landmark period following the first DOAC fill was used to classify patients as abandoners or continuers. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. Time to ischemic stroke/SE was described and compared between cohorts using weighted Kaplan-Meier and Cox proportional hazard models from the end of the landmark period until end of clinical activity or data.

Results

After weighting, 200,398 and 211,352 patients comprised the abandoner and continuer cohorts, respectively. The mean duration of follow-up was 14.9 and 15.7 months, respectively. At 12 months of follow-up, the probability of ischemic stroke/SE was 1.34% in the abandoner cohort and 1.00% in the continuer cohort; the risk of ischemic stroke/SE was 35% higher in the abandoner versus continuer cohort (hazard ratio [95% confidence interval] = 1.35 [1.20, 1.51]; p < 0.0001).

Conclusions

Patients with NVAF who abandoned the first DOAC fill had significantly higher risk of ischemic stroke/SE compared to patients who continued therapy beyond the first fill. There is an unmet need for better access to DOACs so that the long-term risk of poor outcomes may be minimized.

Keywords:

• Direct oral anticoagulants
• ischemic stroke
• nonvalvular atrial fibrillation
• systemic embolism
• treatment abandonment

Transparency

Declaration of funding

This study was funded by Janssen Scientific Affairs, LLC., the producer of rivaroxaban.

Declaration of financial/other relationships

Akshay Kharat and Brahim Bookhart are employees of Janssen Scientific Affairs, LLC, and are stockholders of Johnson & Johnson. Maryia Zhdanava, Dominic Pilon, Gabrielle Caron-Lapointe, and Patrick Lefebvre are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC. Mark J. Alberts has not received compensation for this project.

A reviewer on this manuscript has disclosed that they have been or are a consultant/advisor for Daiichi-Sankyo; Bayer AG and Servier. Peer reviewers on this manuscript have received an honorarium from CMRO for their review work but have no other relevant financial relationships to disclose.

Author contributions

Mark J. Alberts: conceptualization, methodology, resources, writing – original draft preparation, writing – review & editing; Maryia Zhdanava: conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, supervision, validation, visualization, writing – original draft preparation, writing – review & editing; Dominic Pilon: conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, supervision, validation, visualization, writing – original draft preparation, writing – review & editing; Gabrielle Caron-Lapointe: conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, supervision, validation, visualization, writing – original draft preparation, writing – review & editing; Patrick Lefebvre: conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, supervision, validation, visualization, writing – original draft preparation, writing – review & editing; Brahim Bookhart: conceptualization, methodology, resources, writing – original draft preparation, writing – review & editing; Akshay Kharat: conceptualization, funding acquisition, methodology, project administration, resources, writing – original draft preparation, writing – review & editing.

Acknowledgements

Isabelle Ghelerter contributed to the study design and the interpretation of the results for this study and was an employee of Analysis Group, Inc. at the time this study was conducted. Medical writing assistance was provided by Christine Tam, MSc, MWC, an employee of Analysis Group, Inc.

Data availability statement

The datasets generated and analyzed during the current study are not publicly available because they were used pursuant to a data use agreement. The data are available through requests made directly to Symphony Health, an ICON plc Company, via https://www.iconplc.com/contact/.

Ethics statement

Data were de-identified and comply with the patient requirements of the Health Insurance Portability and Accountability Act (HIPAA) of 1996. Studies with de-identified retrospective claims data do not require a waiver of an ethics committee, as per the Health and Human Services Office for Human Research Protections Guidance on Research Involving Coded Private Information or Biological Specimens (Title 45 CFR 46.102(f))¹², they do not meet the definition of human subject research. Throughout the study, researchers complied strictly with all applicable HIPAA data management rules and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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