Clinical InvestigationAcute Ischemic Heart DiseaseAssociation of platelet responsiveness with clopidogrel metabolism: Role of compliance in the assessment of “resistance”
Section snippets
Patients
This analysis represents a cohort of patients with CAD and ischemic stroke treated with clopidogrel. Patients were pooled from multiple databases yielded from 8 cardiology and 4 poststroke protocols, had their platelets tested pre and post clopidogrel therapy for the IPA determination, and were available for follow-up with regard to compliance assessment. The primary study protocols were approved by the various institutional review boards and performed at the different outpatient clinics and/or
Results
The demographics and clinical characteristics in the combined dataset in patients with CAD and after ischemic stroke are presented in Table I.
The age and gender were not distributed evenly between groups. Patients with CAD were younger and more often males. There was a high prevalence of African Americans in the poststroke group when compared with the predominantly white CAD cohort. The distribution of risk factors was also different, when patients with CAD exhibited more frequent family
Discussion
This study, composed of a large mixed population base of patients with CAD and postischemic stroke patients, demonstrates that (a) potential compliance violation with regard to clopidogrel therapy may be reliably detected by measuring plasma level of inactive carboxyl metabolite; (b) noncompliance in the outpatient setting may be associated with inadequate response after clopidogrel and reduced IPA; (c) noncompliance rates are double digit but especially high postischemic stroke; (d) among the
Disclosures
The primary studies were supported in part by the Sanofi-BMS Partnership, Boehringer Ingelheim, Novartis, AtheroGenics, and Johnson and Johnson. The secondary analysis was supported by the Sanofi-BMS Partnership. The sponsors had no role in study design, data collection, data analyses, interpretation of results, or manuscript writing.
Acknowledgements
We thank all the clinical coordinators and laboratory personnel for their outstanding effort.
References (35)
- et al.
Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: a systematic review and meta-analysis
Am Heart J
(2007 Aug) - et al.
Incidence and clinical impact of dual nonresponsiveness to aspirin and clopidogrel in patients with drug-eluting stents
J Am Coll Cardiol
(2008) - et al.
Stent thrombosis is associated with an impaired response to antiplatelet therapy
J Am Coll Cardiol
(2005) - et al.
Noncompliance in clinical trials
Am Heart J
(2005) Prasugrel and cancer risks: potential causes and implications
Am J Med
(2009)- et al.
Aspirin noncompliance is the major cause of “aspirin resistance” in patients undergoing coronary stenting
Am Heart J
(2009) - et al.
Temporal relation between Clopidogrel cessation and stent thrombosis after drug-eluting stent implantation
Am J Cardiol
(2009) A randomized, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events
Lancet
(1996)Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation
N Eng J Med
(2001)- et al.
Clopidogrel for the reduction of events during observation. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial
JAMA
(2002)