Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine: the POBA study (predictor of bleedings with antiplatelet drugs).

Abstract

OBJECTIVES:

This study was designed to define the hyperresponse to thienopyridine (very low on-treatment platelet reactivity [VLTPR]) as the most predictive threshold value of platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP) for the prediction of non-access site-related bleeding events. We also aimed to identify predictors of bleeding and VLTPR in patients treated with thienopyridines.

BACKGROUND:

New P2Y12 blockers and platelet monitoring has been proposed to optimize platelet inhibition after acute coronary syndromes and improve ischemic outcomes. However, bleeding complications remain the Achilles' heel of antiplatelet therapy, and platelet monitoring could be useful to evaluate this risk.

METHODS:

A total of 1,542 consecutive patients undergoing coronary stenting for ACS were included in the present study (287 taking clopidogrel 75 mg, 868 taking clopidogrel 150 mg, and 387 taking prasugrel 10 mg).

RESULTS:

During 6-month follow-up, 9% of patients (n = 139) experienced nonaccess site-related Bleeding Academic Research Consortium bleeding complications. These patients were more often women and nondiabetic and had lower PRI VASP values than others (p < 0.001). Receiver-operating characteristic curve analysis (0.71, p < 0.01) identified a threshold value for VLTPR of PRI VASP ≤10% to predict bleeding events with a sensitivity of 17% and a specificity of 97%. Although prasugrel was the main predictor of VLTPR in the whole population (odds ratio: 10.2, 95% confidence interval: 3.0 to -34.2; p < 0.001), VLTPR was the strongest and independent predictor of bleeding (odds ratio: 4.7, 95% confidence interval: 2.7 to 8.3; p < 0.001).

CONCLUSIONS:

The present study identified VLTPR (PRI VASP ≤10%) as the strongest predictor of bleeding complications in patients treated with thienopyridines. This marker could be useful for tailored therapy and bleeding prevention.

• Authors: Thomas Cuisset, Charlotte Grosdidier, Anderson Diendonné Loundou, Jacques Quilici, Marie Loosveld, Laurence Camoin, Mathieu Pankert, Shirley Beguin, Marc Lambert, Pierre Emmanuel Morange, Jean-Louis Bonnet, Marie-Christine Alessi
• Journal: JACC. Cardiovascular interventions (JACC Cardiovasc Interv) Vol. 6 Issue 8 Pg. 854-63 (Aug 2013) ISSN: 1876-7605 [Electronic] United States
• PMID: 23968703 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Cell Adhesion Molecules
• Microfilament Proteins
• Phosphoproteins
• Piperazines
• Platelet Aggregation Inhibitors
• Thiophenes
• vasodilator-stimulated phosphoprotein
• Clopidogrel
• Prasugrel Hydrochloride
• Ticlopidine

Topics

• Acute Coronary Syndrome (blood, diagnosis, therapy)
• Aged
• Aged, 80 and over
• Area Under Curve
• Biomarkers (blood)
• Cell Adhesion Molecules (blood)
• Clopidogrel
• Coronary Thrombosis (blood, etiology, prevention & control)
• Drug Resistance
• Female
• Hemorrhage (blood, chemically induced, prevention & control)
• Humans
• Logistic Models
• Male
• Microfilament Proteins (blood)
• Middle Aged
• Multivariate Analysis
• Odds Ratio
• Percutaneous Coronary Intervention (adverse effects)
• Phosphoproteins (blood)
• Phosphorylation
• Piperazines (adverse effects)
• Platelet Activation (drug effects)
• Platelet Aggregation Inhibitors (adverse effects)
• Platelet Function Tests
• Prasugrel Hydrochloride
• Prospective Studies
• ROC Curve
• Risk Assessment
• Risk Factors
• Thiophenes (adverse effects)
• Ticlopidine (adverse effects, analogs & derivatives)
• Time Factors
• Treatment Outcome