Oral Anticoagulation and Adverse Outcomes after Ischemic Stroke in Heart Failure Patients without Atrial Fibrillation

https://doi.org/10.1016/j.cardfail.2021.02.017Get rights and content

Abstract

Background

The safety and effectiveness of oral anticoagulation (OAC) after an ischemic stroke in older patients with heart failure (HF) without atrial fibrillation remains uncertain.

Methods

Utilizing Get With The Guidelines Stroke national clinical registry data linked to Medicare claims from 2009-2014, we assessed the outcomes of eligible patients with a history of HF who were initiated on OAC during a hospitalization for an acute ischemic stroke. The cumulative incidences of adverse events were calculated using Kaplan-Meier curves and adjusted Cox proportional hazard ratios were compared between patients discharged on or off OAC.

Results

A total of 8,261 patients from 1,370 sites were discharged alive after an acute ischemic stroke and met eligibility criteria. Of those, 747 (9.0%) were initiated on OAC.  Patients on OAC were younger (77.2±8.0 vs. 80.5±8.9 years, p<0.01). After adjustment for clinical covariates, the likelihood of 1 year mortality was higher in those on OAC (aHR: 1.22, 95% CI 1.05-1.41, p<0.01), while no significant differences were noted for ICH (aHR: 1.34, 95% CI 0.69-2.59, p=0.38) and recurrent ischemic stroke (aHR: 0.78, 95% CI 0.54-1.15, p = 0.21).  The likelihood of all-cause bleeding (aHR: 1.59, 95% CI 1.29-1.96, p<0.01) and all-cause re-hospitalization (aHR: 1.14, 95% CI 1.02-1.27, p = 0.02) was higher for those on OAC.

Conclusion

Initiation of OAC after an ischemic stroke in older patients with HF in the absence of atrial fibrillation is associated with death, bleeding and re-hospitalization without an associated reduction in recurrent ischemic stroke. If validated, these findings raise caution for prescribing OAC to such patients.

Introduction

Heart failure (HF) invokes a hypercoagulable state through reduced flow, abnormalities in hemostasis and platelet dysregulation and endothelial dysfunction.1,2 Activation of these elements from Virchow's triad promotes thrombus formation and increases the risk of cerebral embolism.1 This risk of ischemic stroke persists in the absence of atrial fibrillation and is reported to be 0.69-1.5% per 100 patient years.3 Oral anticoagulation (OAC) reduces the burden of ischemic stroke in patients with co-existent atrial fibrillation and HF.4 However, several randomized clinical trials have failed to show a net benefit of OAC in patients with HF with reduced ejection fraction in sinus rhythm.5,6 The risk of ischemic stroke without concurrent atrial fibrillation remains elevated in HF patients with reduced or preserved ejection fraction7 but the role of OAC in higher risk subgroups remains uncertain.

A prior history of an ischemic stroke is a strong risk factor for recurrence3, but it remains unknown if initiation of OAC, in these higher risk patients with HF without atrial fibrillation, is beneficial. To address this gap in knowledge, we queried a national registry linked to Medicare claims data to assess the safety and clinical effectiveness of OAC after an ischemic stroke in older patients with HF in the absence of atrial fibrillation.

Section snippets

Data Source

The data for this investigation was derived from the American Heart Association and American Stroke Association's Get With The Guidelines-Stroke (GTWG-S) registry. This registry is a voluntary, national, performance initiative which utilizes internet-based entry of cases by participating hospitals to improve delivery of care to patients with stroke. Additional details about the registry have been previously described.8,9 To track outcomes, the registry data was linked to Medicare claims from

Patient Characteristics

The study cohort comprised of 8,261 patients from 1,370 sites who were discharged alive after an admission for an acute ischemic stroke and met the eligibility criteria. They were 80.2±8.8 years old, 61.1% were female, 73.9% were non-Hispanic white, 85.5% had a history of hypertension and 73.5% were admitted to a teaching hospital (table 1). Within the cohort, 747 (9%) were initiated on OAC. Warfarin was utilized as the OAC agent in 678 (90.8%) patients, while the remainder received DOACs.

Discussion

The principal findings of this study which evaluated the clinical utility of OAC after an ischemic stroke in older HF patients without atrial fibrillation are as follows: First, OAC was associated with greater 1-year all-cause mortality. Second, OAC was also associated with a higher likelihood of all-cause bleeding and all-cause rehospitalization. Lastly, although patients on OAC experienced lower numerical incidence of recurrent ischemic stroke, this did not reach statistical significance.

Limitations

This investigation has several limitations. Given the observational and registry based study design we could not eliminate selection bias and residual confounding; however, multivariable regression modeling was conducted to adjust for measured confounders.20 Additional variables that may be associated with OAC and outcomes including socioeconomic status and health literacy were not collected and limit the generalizability of results. Since LVEF was not collected, HF patients were not

Conclusion

In summary, in this national registry-based observational study, initiation of OAC after an ischemic stroke in older HF patients without atrial fibrillation was independently associated with a higher risk of death, bleeding and re-hospitalization without an associated reduction in recurrent ischemic stroke. This elevated morbidity and mortality associated with OAC use raises caution and concerns of safety when considering OAC for such patients and warrants further investigation.

Sources of Funding

Dr Saeed is supported by the National Institutes of Health (NIH)/National Heart, Lung and Blood Institute (K23HL145140). The research described was supported by NIH/National Center for Advancing Translational Science (NCATS) Einstein-Montefiore CTSA Grant (UL1TR002556). The American Heart Association receives a portion of the fees paid by hospitals to the Joint Commission for Primary Stroke Certification. The GWTG-Stroke program is currently supported in part by a charitable contribution from

Role of the Funder/Sponsor

The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclosures

Dr. Fonarow reports receiving research support from the Patient Centered Outcome Research Institute and the National Institutes of Health, and employee of University of California which holds a patent on an endovascular device for stroke. The remaining authors have nothing to disclose.

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