Predicting Bleeding Risk to Guide Aspirin Use for the Primary Prevention of Cardiovascular Disease: A Cohort Study

Ann Intern Med. 2019 Mar 19;170(6):357-368. doi: 10.7326/M18-2808. Epub 2019 Feb 26.

Abstract

Background: Many prognostic models for cardiovascular risk can be used to estimate aspirin's absolute benefits, but few bleeding risk models are available to estimate its likely harms.

Objective: To develop prognostic bleeding risk models among persons in whom aspirin might be considered for the primary prevention of cardiovascular disease (CVD).

Design: Prospective cohort study.

Setting: New Zealand primary care.

Participants: The study cohort comprised 385 191 persons aged 30 to 79 years whose CVD risk was assessed between 2007 and 2016. Those with indications for or contraindications to aspirin and those who were already receiving antiplatelet or anticoagulant therapy were excluded.

Measurements: For each sex, Cox proportional hazards models were developed to predict major bleeding risk; participants were censored at the earliest of the date on which they first met an exclusion criterion, date of death, or study end date (30 June 2017). The main models included the following predictors: demographic characteristics (age, ethnicity, and socioeconomic deprivation), clinical measurements (systolic blood pressure and ratio of total-high-density lipoprotein cholesterol), family history of premature CVD, medical history (smoking, diabetes, bleeding, peptic ulcer disease, cancer, chronic liver disease, chronic pancreatitis, or alcohol-related conditions), and medication use (nonsteroidal anti-inflammatory agents, corticosteroids, and selective serotonin reuptake inhibitors).

Results: During 1 619 846 person-years of follow-up, 4442 persons had major bleeding events (of which 313 [7%] were fatal). The main models predicted a median 5-year bleeding risk of 1.0% (interquartile range, 0.8% to 1.5%) in women and 1.1% (interquartile range, 0.7% to 1.6%) in men. Plots of predicted-against-observed event rates showed good calibration throughout the risk range.

Limitation: Hemoglobin level, platelet count, and body mass index were excluded from the main models because of high numbers of missing values, and the models were not externally validated in non-New Zealand populations.

Conclusion: Prognostic bleeding risk models were developed that can be used to estimate the absolute bleeding harms of aspirin among persons in whom aspirin is being considered for the primary prevention of CVD.

Primary funding source: The Health Research Council of New Zealand.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Aspirin / adverse effects*
  • Aspirin / therapeutic use
  • Cardiovascular Diseases / prevention & control*
  • Female
  • Hemorrhage / chemically induced*
  • Humans
  • Male
  • Middle Aged
  • Primary Prevention*
  • Proportional Hazards Models*
  • Prospective Studies
  • Reproducibility of Results
  • Risk Assessment
  • Risk Factors

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Aspirin