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Direct acting oral anticoagulants

Direct acting oral anticoagulants has been studied in 9 papers since 2018: 1 trial and 5 observational studies in people, 3 reviews; 3 in the past year. It has not reached trials in people. The newest story, Nov 9, 2026: “Women with irregular heartbeat had higher risk of thinking problems”.

InterventionPreclinical

9 papers study it11 findingsUpdated

See all 9 papers on direct acting oral anticoagulants

At a glance

The findings reach people, from one lab or study. 6 independent labs in 6 countries.

“Major bleeding was similar with SD-DOAC vs warfarin in frail, elderly, VKA-experienced patients (HR: 1.06 [95% CI: 0.90-1.25])”
Outcomes in Older Patients After Switching to a Newer Anticoagulant or Remaining on Warfarin: The COMBINE-AF SubstudyJournal of the American College of Cardiology2025doi:10.1016/j.jacc.2025.05.060

None of its findings points the other way.

Humans: a single group. Cells, worms or flies and mice: nothing yet.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

  • 6 independent labs in 6 countries
  • Funders: Brigham and Women's Hospital and 4 more
  • 3 of 10 findings with company ties
  • Human trial1
  • Humans5

Studies in people

1 study gave direct acting oral anticoagulants to people and measured what changed.

What changedDesignPeopleSource

no change: Has no effect on major bleedingHR 1.06, 95% CI 0.90-1.25

no change: Has no effect on net clinical outcomeHR 1.01, 95% CI 0.91-1.13

up: Raises the risk of gastrointestinal bleedingHR 1.83, 95% CI 1.42-2.36

Review of trials27 months median follow-up71,683 people pooled≥75 yearsOlder adults; frailty and VKA-experienced atrial fibrillationJournal of the American College of Cardiology, Aug 7, 2025

What did studies of direct acting oral anticoagulants find?

5

Studies of direct acting oral anticoagulants measured 5 outcomes, among them net clinical outcome, major bleeding and major bleeding.

Net clinical outcome

no changein humans1HR 1.01

1 study

  1. Direct acting oral anticoagulants showed no clear effect on net clinical outcome in humans (frailty and VKA-experienced atrial fibrillation) (HR 1.01, 95% CI 0.91-1.13).

    “Likewise, the net clinical outcome was similar in the frail, elderly, VKA-experienced patients with SD-DOAC vs warfarin (HR: 1.01 [95% CI: 0.91-1.13])”

    Human trialfrailty and VKA-experienced atrial fibrillation27 months median follow-up

    Outcomes in Older Patients After Switching to a Newer Anticoagulant or Remaining on Warfarin: The COMBINE-AF Substudy

    Journal of the American College of Cardiology

Major bleeding

no changein humans1HR 1.06

1 study

  1. Direct acting oral anticoagulants showed no clear effect on major bleeding in humans (frailty and VKA-experienced atrial fibrillation) (HR 1.06, 95% CI 0.90-1.25).

    “Major bleeding was similar with SD-DOAC vs warfarin in frail, elderly, VKA-experienced patients (HR: 1.06 [95% CI: 0.90-1.25])”

    Human trialfrailty and VKA-experienced atrial fibrillation27 months median follow-up

    Outcomes in Older Patients After Switching to a Newer Anticoagulant or Remaining on Warfarin: The COMBINE-AF Substudy

    Journal of the American College of Cardiology

More on Major bleeding

Major bleeding

no changein humans1

1 study

  1. Direct acting oral anticoagulants were not clearly linked with major bleeding in humans (nonvalvular atrial fibrillation in nursing home residents) (aHR 1.03, 95% CI 0.96-1.10).

    “or major bleeding (12.6 vs 12.4 events per 100 person-years; aHR, 1.03; 95% CI, 0.96-1.10)”

    Humansnonvalvular atrial fibrillation in nursing home residents

    Comparative Effectiveness and Safety of Direct Oral Anticoagulants vs Warfarin among Nursing Home Residents with Atrial Fibrillation: A Retrospective Cohort Study

    Journal of the American Medical Directors Association

Ischemic stroke

no changein humans1

1 study

  1. Direct acting oral anticoagulants were not clearly linked with ischemic stroke in humans (nonvalvular atrial fibrillation in nursing home residents) (aHR 0.94, 95% CI 0.84-1.05).

    “there was no statistically significant association between DOAC use and ischemic stroke/systemic embolism [4.5 vs 4.7 events per 100 person-years; adjusted hazard ratio (aHR), 0.94; 95% CI, 0.84-1.05]”

    Humansnonvalvular atrial fibrillation in nursing home residents

    Comparative Effectiveness and Safety of Direct Oral Anticoagulants vs Warfarin among Nursing Home Residents with Atrial Fibrillation: A Retrospective Cohort Study

    Journal of the American Medical Directors Association

More on Ischemic stroke

Quality-adjusted life-years

upin silico1

1 study

  1. Direct acting oral anticoagulants improve quality-adjusted life-years in silico (compared to non-treatment) (0.859 QALYs gained).

    “For each AF treated with DOAC, 0.859 QALYs gained over the lifetime for 65 years-old men, and 0.856 QALYs for 65 years-old women compared to non-treatment.”

    In silicocompared to non-treatmentmalesn = 1,607

    Screening for untreated atrial fibrillation in the elderly population: A community-based study

    PloS one

What is direct acting oral anticoagulants linked with?

6

Studies link direct acting oral anticoagulants with 6 measures, among them mild cognitive impairment, dementia and Positive predictive value of fecal immunochemical testing for advanced neoplasia.

Mild cognitive impairment

downin humans1

1 study

  1. Direct acting oral anticoagulants are linked with a lower risk of mild cognitive impairment in humans (incident non-valvular atrial fibrillation).

    “Non-vitamin-K OAC (NOAC) use was associated with a lower risk of cognitive impairment compared to either warfarin or no OAC in both sexes”

    Humansincident non-valvular atrial fibrillationn = 66,885

    Women with irregular heartbeat had higher risk of thinking problems

    medRxivPreprint

More on Mild cognitive impairment

Dementia

downin humans1

1 study

  1. Direct acting oral anticoagulants lower the risk of dementia in humans (observational data compared with no anticoagulation or warfarin).

    “oral anticoagulation, particularly with direct oral anticoagulants (DOACs), is associated with lower rates of dementia compared with no anticoagulation or warfarin”

    Reviewobservational data compared with no anticoagulation or warfarin

    Atrial Fibrillation and Cognitive Decline: A Systematic Review of Pathophysiological Mechanisms, Therapeutic Strategies, and Digital Health Technologies in Neuroprotection

    Journal of clinical medicine

More on Dementia

Positive predictive value of fecal immunochemical testing for advanced neoplasia

downin humans1OR 0.2

1 study

  1. Direct acting oral anticoagulants are associated with positive predictive value of fecal immunochemical testing for advanced neoplasia in humans (OR 0.20, 95% CI 0.05–0.92; advanced neoplasia diagnosed in 4.0% of users versus 16.8% of non-users).

    “the PPV for AN in the DOAC-user group was significantly lower than that in the non-user group”

    HumansPatients undergoing colonoscopy following positive FIT results; propensity score-matched comparison of users and non-usersn = 818

    Propensity Score-matched Analysis of the Impact of Direct-acting Oral Anticoagulants on Fecal Immunochemical Test Performance

    Journal of the anus, rectum and colon

Gastrointestinal bleeding

upin humans1HR 1.83

1 study

  1. Direct acting oral anticoagulants raise the risk of gastrointestinal bleeding in humans (frailty and VKA-experienced atrial fibrillation) (HR 1.83, 95% CI 1.42-2.36).

    “gastrointestinal bleeding with SD-DOAC was increased to a greater degree in frail, elderly, VKA-experienced patients (HR: 1.83 [95% CI: 1.42-2.36])”

    Human trialfrailty and VKA-experienced atrial fibrillation27 months median follow-up

    Outcomes in Older Patients After Switching to a Newer Anticoagulant or Remaining on Warfarin: The COMBINE-AF Substudy

    Journal of the American College of Cardiology

More on Gastrointestinal bleeding

Mortality

downin humans1

1 study

  1. Direct acting oral anticoagulants are linked with a lower risk of mortality in humans (nonvalvular atrial fibrillation in nursing home residents) (aHR 0.95, 95% CI 0.91-0.98).

    “DOACs use was associated with a modest but statistically significant lower risk of all-cause death (48.1 vs 49.0 events per 100 person-years; IPTW analysis aHR, 0.95; 95% CI, 0.91-0.98).”

    Humansnonvalvular atrial fibrillation in nursing home residents

    Comparative Effectiveness and Safety of Direct Oral Anticoagulants vs Warfarin among Nursing Home Residents with Atrial Fibrillation: A Retrospective Cohort Study

    Journal of the American Medical Directors Association

Osteoporosis

downin humans1

1 study

  1. Direct acting oral anticoagulants are associated with osteoporosis in humans (Patients with atrial fibrillation; compared with warfarin) (aHR 0.79, 95% CI 0.74–0.85; p < 0.001).

    “Overall, DOAC use was associated with a significantly lower risk of a new diagnosis of osteoporosis than warfarin use”

    HumansPatients with atrial fibrillation; compared with warfarinMean follow-up of 841 daysBoth; 39.5% femalesn = 18,454

    Incidence of Osteoporosis in Primary Care Patients with Atrial Fibrillation Receiving Different Oral Anticoagulants

    Journal of clinical medicine

More on Osteoporosis

Latest

Dec 2025: 0Jan 2026: 1Feb 2026: 1Mar 2026: 0Apr 2026: 0May 2026: 0Jun 2026: 0Jul 2026: 1Aug 2026: 0Sep 2026: 0Oct 2026: 0Nov 2026: 03 papers in 12 months
medRxiv

Women with irregular heartbeat had higher risk of thinking problems

Women had a higher risk of memory or thinking problems than men, with an adjusted hazard ratio—a relative-risk measure—of 1.14.Women had a higher risk of memory or thinking problems than men, with an adjusted hazard ratio—a relative-risk measure—of 1.14.

Preprint: cohort · 66,885 peoplePopulations
Paper

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