Antiplatelet Therapy in ACS Patients: Comparing Appropriate P2Y12 Inhibition by Clopidogrel to the Use of New P2Y12 Inhibitors

J Atheroscler Thromb. 2018 Aug 1;25(8):674-689. doi: 10.5551/jat.40584. Epub 2018 Feb 8.

Abstract

Aim: In percutaneous coronary intervention (PCI)-treated acute coronary syndrome (ACS) patients on clopidogrel therapy, high on-treatment platelet adenosine diphosphate (ADP) reactivity was observed in numerous studies, with significant increases in non-fatal myocardial infarction, definite/probable stent thrombosis, or cardiovascular mortality. Compared to clopidogrel, prasugrel and ticagrelor provide more potent platelet inhibition. Whether new P2Y12 inhibitors reduce thrombotic events in a similar manner compared to the rate observed with appropriate P2Y12 inhibition by clopidogrel must still be determined. This study sought to compare long-term outcomes between clopidogrel responders (platelet reactivity index [PRI] vasodilator-stimulated phosphoprotein [VASP] <61%) and patients under prasugrel or ticagrelor therapy following PCI-treated ACS.

Methods: 730 ACS patients undergoing urgent PCI were prospectively enrolled into two groups: clopidogrel responders (n=448) and those under ticagrelor or prasugrel therapy (n=282). The primary endpoint was a composite of cardiovascular death, myocardial infarction, stent thrombosis, and stroke; the secondary endpoint comprised major hemorrhagic events.

Results: The median follow-up was 260±186 days. Clopidogrel patients were older and more likely to present non-ST segment elevation myocardial infarction, cardiovascular risk factors, atrial fibrillation, or prior vascular disease. After propensity score matching, the primary endpoint was met in 7.1% of the clopidogrel group and 4.1% of the prasugrel/ticagrelor group (p=0.43). Minor bleeding events were significantly reduced in the clopidogrel group (1.1% vs. 3%; p=0.03). In a multivariate analysis, the antiplatelet treatment strategy was not an independent primary endpoint predictor.

Conclusion: In PCI-treated ACS patients, clopidogrel therapy and PRI VASP <61% were not associated with increased risks of thrombotic events compared to prasugrel or ticagrelor therapy.

Keywords: Bleeding; Myocardial infarction; Stent; Thrombosis.

Publication types

  • Comparative Study

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Adenosine / analogs & derivatives*
  • Adenosine / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Clopidogrel
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prasugrel Hydrochloride / therapeutic use*
  • Prognosis
  • Prospective Studies
  • Receptors, Purinergic P2Y12 / chemistry*
  • Ticagrelor
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Receptors, Purinergic P2Y12
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticagrelor
  • Adenosine
  • Ticlopidine