Consistent platelet inhibition during long-term maintenance-dose clopidogrel therapy among 359 compliant outpatients with documented vascular disease.

Abstract

BACKGROUND:

Numerous reports have dichotomized responses after clopidogrel therapy using varying definitions and platelet tests in patients immediately after acute vascular events; however, no large study has assessed platelet characteristics in outpatients receiving long-term treatment for more than 30 days with the maintenance dose (75 mg/d) of clopidogrel. The aim of this study was to describe the responses of ex vivo measures of platelet aggregation and activation to long-term clopidogrel therapy in a large population of outpatients after coronary stenting or ischemic stroke.

METHODS:

We conducted a secondary post hoc analysis of a data set represented by presumably compliant patients after coronary stenting (n = 237) or a documented ischemic stroke (n = 122) treated with clopidogrel-and-aspirin combination antiplatelet therapy.

RESULTS:

The mean duration of treatment was 5.8 months (range 1-21 months). Every patient exhibited a significant inhibition of adenosine diphosphate-induced platelet aggregation (mean 52.9%, range 36%-70%) as compared with the preclopidogrel measures. Inhibition of aggregation strongly correlated with a diminished expression of PECAM-1 (platelet/endothelial cell adhesion molecule 1, r = 0.75), glycoprotein IIb/IIIa (r = 0.62), and PAR-1 (protease-activated receptor 1, r = 0.71). None of the patients developed hyporesponsiveness (reduction from the baseline <15%) or profound inhibition (residual platelet activity <10%).

CONCLUSIONS:

In contrast to the wide variability of responses that exists in the acute setting, long-term therapy with clopidogrel leads to consistent and much less variable platelet inhibition. Lack of nonresponse and profound inhibition with clopidogrel allow for the maintenance of a delicate balance between proven efficacy and acceptable bleeding risks for long-term secondary prevention in outpatients after acute vascular events.

• Authors: Victor L Serebruany, Alex I Malinin, Dan Atar, Dan F Hanley
• Journal: American heart journal (Am Heart J) Vol. 153 Issue 3 Pg. 371-7 (Mar 2007) ISSN: 1097-6744 [Electronic] United States
• PMID: 17307414 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Integrin beta3
• Platelet Aggregation Inhibitors
• Platelet Endothelial Cell Adhesion Molecule-1
• Platelet Membrane Glycoprotein IIb
• Clopidogrel
• Ticlopidine
• Aspirin

Topics

• Aged
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Aspirin (therapeutic use)
• Clopidogrel
• Drug Therapy, Combination
• Female
• Flow Cytometry
• Humans
• Integrin beta3 (blood)
• Male
• Middle Aged
• Patient Compliance
• Platelet Aggregation Inhibitors (administration & dosage)
• Platelet Endothelial Cell Adhesion Molecule-1 (blood)
• Platelet Function Tests
• Platelet Membrane Glycoprotein IIb (blood)
• Risk Factors
• Ticlopidine (administration & dosage, analogs & derivatives)
• Vascular Diseases (drug therapy, epidemiology, physiopathology)