Inhibition of platelet aggregation by aspirin progressively decreases in long-term treated patients

J Am Coll Cardiol. 2004 Mar 17;43(6):979-84. doi: 10.1016/j.jacc.2003.08.062.


Objectives: We sought to investigate, during a two-year follow-up period, the effects of aspirin on platelet aggregation.

Background: The platelets of patients given aspirin may be less sensitive to antiplatelet treatment, although the extent of such phenomenon over long-term follow-up is unclear.

Methods: Adenosine diphosphate (ADP) and collagen-induced platelet aggregation was periodically monitored before and after 2, 6, 12, and 24 months of treatment with aspirin (n = 150) or ticlopidine (n = 80) in patients matched for gender, age, and risk factors for atherothrombosis.

Results: Compared with baseline values, two months of aspirin treatment significantly inhibited platelet aggregation; thereafter, this inhibitory effect progressively decreased. At 24-month follow-up, collagen-induced platelet aggregation was significantly higher than that observed at two months (p < 0.05); a more pronounced difference was observed when collagen-induced lag phase was considered (p < 0.01). Restoration of platelet aggregation was less evident when ADP was used as an agonist. Conversely, the inhibition induced by ticlopidine was constant throughout follow-up with both agonists.

Conclusions: The study demonstrates that a long-term treatment with aspirin is associated with a progressive reduction in platelet sensitivity to this drug.

Publication types

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

MeSH terms

  • Adenosine Diphosphate
  • Aged
  • Aspirin / pharmacology*
  • Collagen
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / pharmacology*
  • Ticlopidine / pharmacology*


  • Platelet Aggregation Inhibitors
  • Adenosine Diphosphate
  • Collagen
  • Ticlopidine
  • Aspirin