title: Profile and prevalence of clopidogrel resistance in patients of acute coronary syndrome.
abstract: Recently reports of a variable platelet response to aspirin and potential resistance to therapy have emerged with thienopyridines group of drugs. However the data available on clopidogrel resistance is scarce. The present study was initiated to prospectively evaluate the prevalence of clopidogrel resistance in patients of acute coronary syndrome(ACS) presently on dual anti platelet therapy by using an established method of optical platelet aggregation. We studied 39 patients of ACS, who were on clopidogrel 300 mg bolus followed by 75 mg per day for 3 days along with aspirin 325 mg per day. Fasting blood samples were assessed using optical platelet aggregation (Chronolog Corp, USA). Clopidogrel resistance was defined as <10% decrease from baseline in platelet aggregation. Clopidogrel semi-responders were defined as 10-29% ( <30%) decrease from baseline in platelet aggregation. Clopidogrel non-responders were defined as a composite of resistant and semi-responders. A baseline mean platelet aggregation obtained from 18 healthy subjects was 63.8 +/- 14.75% with 5 mu and 68.8 +/-13.91% with 10 mu of Adenosine Diphosphate. Hence, the definition of clopidogrel resistance was set as aggregation of >57% with 5 mu ADP and >61.9% with 10 mu ADP (< 10% decrease from baseline). The definition of clopidogrel semi-responder was set as aggregation of >or=45% with 5 mu ADP and >or=48% with 10 mu ADP (10-29% decrease from baseline). The mean platelet aggregation with 5 mu and 10 mu of Adenosine Diphosphate in the patient group was 30.77 +/- 17.19% and 35.71 +/- 17.0% respectively. Based on these criteria, 2.54% patients were found to be clopidogrel resistant, 12.7% were clopidogrel semi-responders and 84.7% were clopidogrel responders. On comparison of clopidogrel responders with non-responders, females ( p=0.07) and patients with higher serum triglyceride levels (p=0.08), had a trend to be more inclined towards clopidogrel non-responders. All other parameters tested namely age, smoking, diabetes, hypertension, obesity, cholesterol, hemoglobin, platelet count, ejection fraction and concurrent drug intake did not show any statistically significant difference among the groups.
  
  
  CONCLUSIONS
  This study shows that clopidogrel resistant and clopidogrel semi-responders do occur in Indian patients with ACS and there are no reliable clinical predictors for this condition. The diagnosis therefore relies primarily on laboratory tests.
authors.affiliation: Department of Cardiology, King George Medical University, Lucknow.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.forename: Ram K
authors.initials: RK
authors.lastname: Saran
authors.forename: Aniket
authors.initials: A
authors.lastname: Puri
authors.forename: Nishant
authors.initials: N
authors.lastname: Gupta
authors.forename: Rishi
authors.initials: R
authors.lastname: Sethi
authors.forename: W R
authors.initials: WR
authors.lastname: Surin
authors.forename: Madhu
authors.initials: M
authors.lastname: Dikshit
authors.forename: Sudhanshu K
authors.initials: SK
authors.lastname: Dwivedi
authors.forename: Varun S
authors.initials: VS
authors.lastname: Narain
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Puri
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000077144:Clopidogrel; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine