Journal Article

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

Yanez-Lopez, Monica, Stables, Rod H., Karathanos, Athanasios, Geisler, Tobias, Dalby, Miles, Davidson, Simon J., Gawaz, Meinrad, Flather, Marcus, Müller, Karin, Tavlaki, Elli, Booth, Jean, Droppa, Michal, Banya, Winston, Zaman, Azfar

2015

Overview

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. 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 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. 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. 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. ClinicalTrials.gov NCT01339026.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acute Coronary Syndrome - blood / Acute Coronary Syndrome - therapy / Acute coronary syndromes / Adenosine diphosphate / Adenosine Diphosphate - metabolism / Adenosine Diphosphate - pharmacology / Aged / Angioplasty / Blood Platelets - drug effects / Clinical trials / Clopidogrel / Disorders / Drugs / Female / Follow-Up Studies / Genotype & phenotype / Hospitals / Humans / Intervention / Male / Middle Aged / Patients / Percutaneous Coronary Intervention - adverse effects / Platelet Activation - drug effects / Platelet aggregation / 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 / Randomization / Reactivity / Risk Factors / Task forces / Thoracic surgery / Ticlopidine - analogs & derivatives / Ticlopidine - pharmacology / Ticlopidine - therapeutic use / Treatment Outcome