Long-Term Population-Based Cerebral Ischemic Event and Cognitive Outcomes of Direct Oral Anticoagulants Compared With Warfarin Among Long-term Anticoagulated Patients for Atrial Fibrillation

Topic: Risk, prevention and care in population studies

Direct oral anticoagulants (DOACs) have been used in clinical practice in the United States for the last 4 to 6 years. Although DOACs may be an attractive alternative to warfarin in many patients, long-term outcomes of use of these medications are unknown. We performed a propensity-matched analysis to report patient important outcomes of death, stroke/transient ischemic attack (TIA), bleeding, major bleeding, and dementia in patients taking a DOAC or warfarin. Patients receiving long-term anticoagulation from June 2010 to December 2014 for thromboembolism prevention with either warfarin or a DOAC were matched 1:1 by index date and propensity score. Multivariable Cox hazard regression was performed to determine the risk of death, stroke/TIA, major bleed, and dementia by the anticoagulant therapy received. A total of 5,254 patients were studied (2,627 per group). Average age was 72.4 ± 10.9 years, and 59.0% were men. Most patients were receiving long-term anticoagulation for AF management (warfarin: 96.5% vs DOAC: 92.7%, p <0.0001). Rivaroxaban (55.3%) was the most commonly used DOAC, followed by apixaban (22.5%) and dabigatran (22.2%). The use of DOACs compared with warfarin was associated with a reduced risk of long-term adverse outcomes: death (p = 0.09), stroke/TIA (p <0.0001), major bleed (p <0.0001), and bleed (p = 0.14). No significant outcome variance was noted in DOAC-type comparison. In the AF multivariable model patients taking DOAC were 43% less likely to develop stroke/TIA/dementia (hazard ratio 0.57 [CI 0.17, 1.97], p = 0.38) than those taking warfarin. Our community-based results suggest better long-term efficacy and safety of DOACs compared with warfarin. DOAC use was associated with a lower risk of cerebral ischemic events and new-onset dementia.

Key findings

• The use of DOACs compared with warfarin was associated with a reduced risk of long-term adverse outcomes: death (p = 0.09), stroke/TIA (p <0.0001), major bleed (p <0.0001), and bleed (p = 0.14).
• No significant outcome variance was noted in DOAC-type comparison.
• Our community-based results suggest better long-term efficacy and safety of DOACs compared with warfarin.
• DOAC use was associated with a lower risk of cerebral ischemic events and new-onset dementia.

Why it matters

In patients on long-term anticoagulation for atrial fibrillation, use of direct oral anticoagulants was associated with a lower risk of new-onset dementia compared with warfarin. The study also found reduced risks of stroke/TIA and major bleeding with DOACs.

New to this subject? Start with our plain-English guide: Prevention →

Study details

• Participants5,254
• Effect size59.0%; 96.5%; 92.7%
• Evidence strengthLow

Read the original

• DOI: 10.1016/j.amjcard.2016.04.039
• PubMed: 27236255
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{jacobs2016-27236255,
  author  = {Jacobs, V. and May, H. T. and Bair, T. L. and Crandall, B. G. and Cutler, M. J. and Day, J. D. and Mallender, C. and Osborn, J. S. and others},
  title   = {{Long-Term Population-Based Cerebral Ischemic Event and Cognitive Outcomes of Direct Oral Anticoagulants Compared With Warfarin Among Long-term Anticoagulated Patients for Atrial Fibrillation}},
  journal = {The American journal of cardiology},
  year    = {2016},
  doi     = {10.1016/j.amjcard.2016.04.039},
  pmid    = {27236255},
  url     = {https://doi.org/10.1016/j.amjcard.2016.04.039}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Atrial fibrillation is independently associated with senile, vascular, and Alzheimer's dementia Heart rhythm · 2009-12-11 · usefulness score 56/100 · Getting a diagnosis

Later studies that cite this one

1 study in the alzhub library lists this one in its references.

• Vascular cognitive impairment Nature reviews. Disease primers · 2018-02-15 · usefulness score 55/100 · Prevention and risk

Related studies in Prevention and risk

• Warfarin use among patients with atrial fibrillation Stroke · 1997-12-01 · usefulness score 50/100
• Atrial Fibrillation: Epidemiology, Pathophysiology, and Clinical Outcomes Circulation research · 2017-04-01 · usefulness score 53/100
• What predicts mortality in Parkinson disease?: a prospective population-based long-term study Neurology · 2010-10-01 · usefulness score 58/100
• Heart diseases and long-term risk of dementia and Alzheimer's disease: a population-based CAIDE study Journal of Alzheimer's disease : JAD · 2014-01-01 · usefulness score 55/100
• Novel risk markers and long-term outcomes of delirium: the successful aging after elective surgery (SAGES) study design and methods Journal of the American Medical Directors Association · 2012-09-19 · usefulness score 60/100
• Long-term health outcomes in a British cohort of breast, colorectal and prostate cancer survivors: a database study British journal of cancer · 2011-11-01 · usefulness score 57/100

Similar studies

• Atrial fibrillation and stroke prevention with warfarin in the long-term care setting 1997 · Clinical safety
• Impact of anticoagulation on cognitive decline and clinical outcomes in patients with atrial fibrillation and dementia: A retrospective cohort study 2026 · Cognitive tests and assessment
• Continued Use of Warfarin in Veterans with Atrial Fibrillation After Dementia Diagnosis 2016 · Health systems and care delivery
• Initiation and persistence of warfarin or aspirin in patients with chronic atrial fibrillation in general practice: do the appropriate patients receive stroke prophylaxis? 2008 · Clinical safety
• Trends in Use of Oral Anticoagulants in Older Adults With Newly Diagnosed Atrial Fibrillation, 2010-2020 2022 · Health systems and care delivery
• Risk of dementia in stroke-free patients diagnosed with atrial fibrillation: data from a population-based cohort 2019 · Vascular contributions

More on Prevention and risk

• A review that covers this ground Atrial Fibrillation: A Review JAMA · 2025-01-01 · usefulness score 57/100
• Newest in this subject Constraint Based Metabolic Modeling Identifies Robust Biomarkers and Therapeutic Target Combinations in Alzheimer Disease Research Square · 2026-10-15 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject The Gut–Liver–Brain Axis in Neurodegeneration: Unraveling Metabolic–Immune Crosstalk from Peripheral Sensing to Central Vulnerability Preprints.org · 2026-10-08 · Preprint — not yet peer-reviewed · usefulness score 16/100

See all studies in Prevention and risk →