Switching acute coronary syndrome patients from prasugrel to clopidogrel

JACC Cardiovasc Interv. 2013 Feb;6(2):158-65. doi: 10.1016/j.jcin.2012.09.012.

Abstract

Objectives: This study sought to assess the consequences of switching prasugrel to clopidogrel on platelet inhibition and clinical outcomes after an acute coronary syndrome (ACS).

Background: Many ACS patients are switched from prasugrel to clopidogrel within the recommended 1-year duration of treatment.

Methods: Platelet reactivity was measured with the VerifyNow P2Y(12) assay (Accumetrics, San Diego, California) in 300 ACS patients treated for 15 days with prasugrel 10 mg. Patients displaying low on-treatment platelet reactivity (LPR) and/or at high risk of bleeding were switched to clopidogrel 75 mg and tested again 15 days later. The rate of patients with high on-treatment platelet reactivity (HPR), P2Y(12) reaction units (PRU) >208, and LPR (PRU <0) were evaluated before and after the switch. Bleeding and ischemic events were also recorded.

Results: On a regimen of prasugrel 10 mg, the rate of patients with LPR was 45.6% (n = 137), whereas 4.3% (n = 13) had HPR. A group of 31 patients (10.3%) was switched to clopidogrel 75 mg, of whom 29 had LPR (93.5%) on a regimen of prasugrel. On-treatment platelet reactivity (PRU) increased from 14 ± 4 on a regimen of prasugrel to 155 ±15 on a regimen of clopidogrel (p = 0.0001), resulting in a much lower rate of patients with LPR (9.7%). The rate of patients with HPR increased from 0% with prasugrel to 29% (n = 9) with clopidogrel. The rate of minor bleeding decreased after the switch from 32.2% to 9.7%; p = 0.03.

Conclusions: An LPR is frequent in patients treated with prasugrel 10 mg. Early switching from prasugrel 10 mg to clopidogrel 75 mg reduces the number of patients with LPR and minor bleeding events but unmasks a group of nonresponders to clopidogrel with unknown consequences on clinical outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / drug therapy*
  • Aged
  • Biomarkers / blood
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Cell Adhesion Molecules / blood
  • Chi-Square Distribution
  • Clopidogrel
  • Drug Resistance
  • Drug Substitution*
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Microfilament Proteins / blood
  • Middle Aged
  • Phosphoproteins / blood
  • Phosphorylation
  • Piperazines / administration & dosage*
  • Piperazines / adverse effects
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Function Tests
  • Prasugrel Hydrochloride
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / administration & dosage*
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Receptors, Purinergic P2Y12 / blood
  • Receptors, Purinergic P2Y12 / drug effects
  • Registries
  • Risk Assessment
  • Risk Factors
  • Thiophenes / administration & dosage*
  • Thiophenes / adverse effects
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Cell Adhesion Molecules
  • Microfilament Proteins
  • P2RY12 protein, human
  • Phosphoproteins
  • Piperazines
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12
  • Thiophenes
  • vasodilator-stimulated phosphoprotein
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticlopidine