Dual non-responsiveness to antiplatelet treatment is a stronger predictor of cardiac adverse events than isolated non-responsiveness to clopidogrel or aspirin

Int J Cardiol. 2013 Jul 31;167(2):430-5. doi: 10.1016/j.ijcard.2012.01.016. Epub 2012 Feb 2.


Background: High platelet reactivity (HPR) under treatment with clopidogrel or aspirin is associated with adverse outcome. We aimed to investigate whether high platelet reactivity (HPR) to both aspirin and clopidogrel is a stronger predictor of adverse events compared to isolated HPR to clopidogrel or aspirin.

Methods: In this prospective cohort study platelet reactivity to adenosine diphosphate (ADP) and arachidonic acid (AA) was assessed by Multiple Electrode Aggregometry (MEA) in 403 patients undergoing percutaneous coronary intervention. The rates of the composite of cardiac adverse events (acute coronary syndrome, stent thrombosis, stroke, death and revascularization) were recorded during 12-month follow-up.

Results: The composite endpoint of cardiovascular adverse events occurred more often in patients with high platelet reactivity (HPR) to both agonists ADP and AA (37.5%) than in those with isolated HPR to ADP (33.3%), AA (25.6%) or without any HPR (18.6%; p=0.003). Classification tree analysis indicated that any HPR emerged as an independent predictor influencing outcome, which was associated with a 1.75 higher risk of cardiac adverse events (OR=1.75: 95%CI=1.1-2.9). Interestingly, the predictive value of HPR tended to be greater among patients with diabetes mellitus (OR=2.18; 95%CI=1.20-3.95). C-reactive protein and diabetes mellitus were independent predictors of high platelet reactivity to both agonists.

Conclusions: Dual low responsiveness to clopidogrel and aspirin is a strong predictor of cardiac adverse events, especially in patients with diabetes mellitus, which underlines the need for personalized antiplatelet treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin / administration & dosage*
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / drug therapy*
  • Clopidogrel
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation / drug effects
  • Platelet Aggregation / physiology*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Predictive Value of Tests
  • Prospective Studies
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Treatment Outcome


  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Aspirin