Bleeding Risks With Aspirin Use for Primary Prevention in Adults: A Systematic Review for the U.S. Preventive Services Task Force

Ann Intern Med. 2016 Jun 21;164(12):826-35. doi: 10.7326/M15-2112. Epub 2016 Apr 12.


Background: The balance between potential aspirin-related risks and benefits is critical in primary prevention.

Purpose: To evaluate the risk for serious bleeding with regular aspirin use in cardiovascular disease (CVD) primary prevention.

Data sources: PubMed, MEDLINE, Cochrane Central Register of Controlled Trials (2010 through 6 January 2015), and relevant references from other reviews.

Study selection: Randomized, controlled trials; cohort studies; and meta-analyses comparing aspirin with placebo or no treatment to prevent CVD or cancer in adults.

Data extraction: One investigator abstracted data, another checked for accuracy, and 2 assessed study quality.

Data synthesis: In CVD primary prevention studies, very-low-dose aspirin use (≤100 mg daily or every other day) increased major gastrointestinal (GI) bleeding risk by 58% (odds ratio [OR], 1.58 [95% CI, 1.29 to 1.95]) and hemorrhagic stroke risk by 27% (OR, 1.27 [CI, 0.96 to 1.68]). Projected excess bleeding events with aspirin depend on baseline assumptions. Estimated excess major bleeding events were 1.39 (CI, 0.70 to 2.28) for GI bleeding and 0.32 (CI, -0.05 to 0.82) for hemorrhagic stroke per 1000 person-years of aspirin exposure using baseline bleeding rates from a community-based observational sample. Such events could be greater among older persons, men, and those with CVD risk factors that also increase bleeding risk.

Limitations: Power to detect effects on hemorrhagic stroke was limited. Harms other than serious bleeding were not examined.

Conclusion: Consideration of the safety of primary prevention with aspirin requires an individualized assessment of aspirin's effects on bleeding risks and expected benefits because absolute bleeding risk may vary considerably by patient.

Primary funding source: Agency for Healthcare Research and Quality.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aspirin / administration & dosage
  • Aspirin / adverse effects*
  • Cardiovascular Diseases / prevention & control*
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / adverse effects*
  • Gastrointestinal Hemorrhage / chemically induced*
  • Hemorrhage / chemically induced
  • Humans
  • Primary Prevention*
  • Risk Factors
  • Stroke / chemically induced*


  • Fibrinolytic Agents
  • Aspirin