title: The ELAPSE (Evaluation of Long-Term Clopidogrel Antiplatelet and Systemic Anti-Inflammatory Effects) study.
abstract: OBJECTIVE
  This study was designed to evaluate the effects of long-term clopidogrel and aspirin administration on platelet aggregation, activation, and inflammation.
  
  
  BACKGROUND
  Clopidogrel resistance was described in 15% to 30% of patients with short-term therapy, but its antiplatelet effects with long-term therapy is unknown.
  
  
  METHODS
  We performed a prospective study of patients undergoing coronary stenting who were on aspirin for > or =5 days but not previously on clopidogrel. Clopidogrel 600 mg was given before stenting. Clopidogrel 75 mg/day and aspirin 325 mg/day were continued for 1 year. Light-transmittance aggregometry with 5-micromol/l adenosine diphosphate and 1-mmol/l arachidonic acid stimulation; VerifyNow clopidogrel and aspirin assays; platelet activation receptor expression of CD40L, CD62P, and PAC-1 (antibody against activated glycoprotein IIb/IIIa); and inflammatory markers of soluble CD40L and P-selectin, high-sensitivity C-reactive protein, interleukin-10, and interleukin-18 were measured at baseline; 1 day; and 1, 6, and 12 months. Our primary analysis compared light-transmittance aggregometry aggregation at 1 versus 12 months.
  
  
  RESULTS
  We enrolled 26 patients who completed a 1-year follow-up. Maximal platelet adenosine diphosphate-stimulated aggregation was 61.8 +/- 25.9% at baseline, 22.1 +/- 18.3% at 1 day, 30.6 +/- 16.8% at 1 month, 29.0 +/- 13.3% at 6 months, and 26.7 +/- 13.6% at 12 months (p = 0.099 for 12 months vs. 1 month). VerifyNow clopidogrel platelet inhibition was similar at 12 months versus 1 month (38.9 +/- 19.7% vs. 45.6 +/- 26.7%, p = 0.578). Likewise, there was no difference in aspirin's effects on platelet aggregation at 12 months versus 1 month. In contrast, platelet activation receptor expression of CD40L, CD62P, and PAC-1 were higher at 12 months versus 1 month.
  
  
  CONCLUSIONS
  Our pilot study showed no attenuation of clopidogrel's effects on platelet aggregation with long-term administration. However, platelet activation receptor expression increased with time and should be further evaluated.
authors.affiliation: Division of Cardiology, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: jsaw@interchange.ubc.ca.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Saw
authors.affiliation: Canadian Blood Services, Vancouver, British Columbia, Canada.
authors.forename: Esben Hjorth
authors.initials: EH
authors.lastname: Madsen
authors.affiliation: Canadian Blood Services, Vancouver, British Columbia, Canada.
authors.forename: Sammy
authors.initials: S
authors.lastname: Chan
authors.affiliation: Department of Pathology and Laboratory Medicine and Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada; Canadian Blood Services, Vancouver, British Columbia, Canada; Division of Cardiology, St. Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Maurer-Spurej
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011446:Prospective Studies; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin