High Platelet Reactivity in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Randomised Controlled Trial Comparing Prasugrel and Clopidogrel

PLoS One. 2015 Aug 28;10(8):e0135037. doi: 10.1371/journal.pone.0135037. eCollection 2015.

Abstract

Background: Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited.

Objectives: To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS).

Patients: Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. "poor responders" were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors.

Results: At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively.

Conclusions: Routine platelet function testing identifies patients with high residual platelet reactivity ("poor responders") on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit.

Trial registration: ClinicalTrials.gov NCT01339026.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / therapy*
  • Adenosine Diphosphate / metabolism
  • Adenosine Diphosphate / pharmacology
  • Aged
  • Blood Platelets / drug effects*
  • Clopidogrel
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention* / adverse effects
  • Platelet Activation* / drug effects
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use
  • Prasugrel Hydrochloride / pharmacology
  • Prasugrel Hydrochloride / therapeutic use*
  • Purinergic P2Y Receptor Antagonists / pharmacology
  • Purinergic P2Y Receptor Antagonists / therapeutic use
  • Risk Factors
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology
  • Ticlopidine / therapeutic use
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Adenosine Diphosphate
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticlopidine

Associated data

  • ClinicalTrials.gov/NCT01339026

Grants and funding

This work was supported by an Investigator Initiated Trial grant by Daiichi Sankyo/Eli Lilly, the NIHR Cardiovascular Biomedical Research Unit of Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, and in part by the National Health Service Foundation Trust and the German Ministry of Education and Research, the Deutsche Forschungsgemeinschaft, and the Klinische Forschergruppe KFO274 “Platelets-Basic Mechanisms and Translational Implications”. TG was personally funded by the ‘Atherothrombosis Research Grant’ from the European Society of Cardiology. Eli Lilly/Daiichi Sankyo (TG, MD, MF, MG, AZ), The Medicines Company (TG, RS), Bayer Health Care(TG), Bristol Myer Squibb(TG), Pfizer (TG), Boehringer Ingelheim (TG), Astra Zeneca (TG, MD, MF, RS, MG, AZ), Boston Scientific (MD), Medtronic (MD), Abbot Vascular (MD), GSK (MF), Novartis (MF), Organon (SD), Mitsubishi Pharma (SD), Bayer (SD), Werfen China (SD), Instrumentation Laboratory (SD) and Sanofi (MG, AZ) provided support in the form of salaries for authors, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.