Determinants of reduced antiplatelet effect of aspirin in patients with stable coronary artery disease

PLoS One. 2015 May 18;10(5):e0126767. doi: 10.1371/journal.pone.0126767. eCollection 2015.

Abstract

Background: Aspirin is a cornerstone in management of coronary artery disease (CAD). However, considerable variability in the antiplatelet effect of aspirin has been reported.

Aim: To investigate independent determinants of reduced antiplatelet effect of aspirin in stable CAD patients.

Methods: We performed a cross-sectional study including 900 stable, high-risk CAD patients. Among these, 795 (88%) had prior myocardial infarction, 250 (28%) had type 2 diabetes, and 170 (19%) had both. All patients received 75 mg aspirin daily as mono antiplatelet therapy. The antiplatelet effect of aspirin was assessed by measurement of platelet aggregation employing 1) multiple electrode aggregometry (MEA, Multiplate Analyzer) in whole blood anticoagulated with citrate or hirudin using arachidonic acid (AA) or collagen as agonists, and 2) VerifyNow Aspirin Assay. Compliance was assessed by measurement of serum thromboxane B2.

Results: Platelet count, prior myocardial infarction, type 2 diabetes and body mass index were independent determinants of increased AA-induced MEA platelet aggregation in citrate and hirudin anticoagulated blood (p-values ≤ 0.045). Similar results were found with VerifyNow. Prior coronary artery bypass grafting, age, smoking (MEA, AA/citrate) and female gender (MEA, AA/hirudin) were also independent determinants of increased platelet aggregation (p-values ≤ 0.038). Compliance was confirmed by low serum thromboxane B2 levels in all patients (median [25%;75%]: 0.97 [0.52;1.97], range 0.02-26.44 ng/ml).

Conclusion: Platelet count, prior myocardial infarction, type 2 diabetes and body mass index were independent determinants of increased platelet aggregation, indicating that these characteristics may be key factors in reduced antiplatelet effect of aspirin in stable CAD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin / blood*
  • Body Mass Index
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / drug therapy*
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / complications
  • Myocardial Infarction / drug therapy
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Count
  • Thromboxane B2 / blood

Substances

  • Platelet Aggregation Inhibitors
  • Thromboxane B2
  • Aspirin

Grant support

The study was financially supported by the Danish Agency for Science, Technology and Innovation (grant no. 2101-05-0052, SDK), the Faculty of Health Sciences, Aarhus University, Denmark (SBL); The Danish Heart Foundation (SBL); Department of Clinical Medicine, Aarhus University Hospital, Denmark (SNP); Eva & Henry Fraenkel’s Foundation (SBL); Aase & Ejnar Danielsen’s Foundation (SBL); Sophus Jacobsen & Spouse Astrid Jacobsen’s Foundation (SBL); The Korning Foundation (SBL); The Physician’s assurance association anno 1891 (SBL) and Carl & Ellen Hertz's Grant to Danish Medical- and Natural Science (SBL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.