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Bleeding Risk With Combining Antiplatelets and Anticoagulants for Secondary Stroke Prevention: A Propensity

Salia Farrokh1,2, Krishna Nalleballe3, Sanjeeva Onteddu3

  • 1Division of Neurosciences Critical Care, Department of Anesthesiology and Critical Care Medicine, Neurology, and Neurosurgery Johns Hopkins University School of Medicine Baltimore MD USA.

Journal of the American Heart Association
|August 20, 2025
PubMed
Summary

Combining antiplatelets with anticoagulants for stroke patients increases long-term hemorrhage risk, particularly intracerebral bleeding beyond 12 months. Gastrointestinal bleeding risk is elevated acutely and long-term with these combination therapies.

Keywords:
acute gastrointestinal bleeding riskacute ischemic strokeacute myocardial infarctionanticoagulationantiplatelet therapyatrial fibrillationintracerebral hemorrhage risk

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Area of Science:

  • Cardiology
  • Neurology
  • Pharmacology

Background:

  • Limited data exist on the safety of combining antiplatelet and anticoagulant therapies for secondary stroke prevention in acute ischemic stroke (AIS).
  • Hemorrhage risk associated with these combinations in patients with concomitant atrial fibrillation and acute myocardial infarction is not well-established.

Purpose of the Study:

  • To examine the hemorrhage risk associated with combining single (SAPT) or dual antiplatelet therapy (DAPT) with anticoagulants.
  • To compare this risk in patients with AIS, atrial fibrillation, and acute myocardial infarction.

Main Methods:

  • Retrospective cross-sectional cohort study using TriNetX data from 76 US hospitals.
  • Propensity score-matched analysis comparing anticoagulant alone, anticoagulant plus SAPT, and anticoagulant plus DAPT subcohorts.
  • Evaluation of acute spontaneous intracerebral hemorrhage and gastrointestinal bleeding risk at 3 months, 12 months, and throughout follow-up.

Main Results:

  • Among 144,434 patients, 8772 received anticoagulants alone, 88,430 received anticoagulant plus SAPT, and 47,232 received anticoagulants plus DAPT.
  • No significant increase in intracerebral hemorrhage risk at 3 and 12 months with combination therapies compared to anticoagulant alone.
  • Increased long-term intracerebral hemorrhage risk (OR 1.26 for SAPT, 1.34 for DAPT) and elevated gastrointestinal bleeding risk at all time points.

Conclusions:

  • Combining antiplatelets with anticoagulants after AIS may increase long-term intracerebral hemorrhage risk, especially beyond 12 months.
  • Combination therapies are associated with an increased risk of acute and long-term gastrointestinal bleeding.
  • Larger prospective studies are needed to confirm these findings.