title: Aspirin plus clopidogrel for optimal platelet inhibition following off-pump coronary artery bypass surgery: results from the CRYSSA (prevention of Coronary arteRY bypaSS occlusion After off-pump procedures) randomised study.
abstract: OBJECTIVE
  To determine the individual variability in the response to aspirin and/or clopidogrel and its impact on graft patency after off-pump coronary artery bypass grafting.
  
  
  METHODS
  A single-centre prospective randomised controlled study designed according to the Consolidated Standards of Reporting Trials statement. Randomisation was obtained by a computer-generated algorithm.
  
  
  METHODS
  University medical school in Italy.
  
  
  METHODS
  300 patients who underwent off-pump coronary artery bypass grafting were randomised to receive aspirin (n=150) or aspirin plus clopidogrel (n=150).
  
  
  METHODS
  Aspirin 100 mg or aspirin 100 mg plus clopidogrel 75 mg daily was initiated when postoperative chest tube drainage was ≤ 50 ml/h for 2 h and patients were followed up for 12 months.
  
  
  METHODS
  Qualitative and quantitative assessment of platelet function, angiographic evaluation of coronary revascularisation by 64-slice CT and clinical outcome.
  
  
  RESULTS
  In the aspirin group, 49 patients (32.6%) were aspirin resistant and, in the aspirin-clopidogrel group, 19 patients (12.6%) were aspirin and clopidogrel resistant. The platelet response to aspirin was similar in all aspirin responders despite the study arm (Aspirin Reaction Units 313.2 ± 44.8 vs 323.6 ± 53.6; p=0.07). The platelet response to clopidogrel was enhanced by aspirin in patients responsive to both aspirin and clopidogrel (synergistic effect) compared with responders to clopidogrel only (P2Y12 Reaction Units 139.9 ± 15.5 vs 179.4 ± 18.5; p<0.001). Combined therapy was associated with a reduced vein graft occlusion rate (7.4% vs 13.1%; p=0.04). Antiplatelet resistance was a predictor of graft occlusion (RR 3.6, 95% CI 2.5 to 6.9; p<0.001). Synergistic aspirin and clopidogrel activity was a strong predictor of vein graft patency (RR 5.1, 95% CI 1.4 to 16.3; p<0.01).
  
  
  CONCLUSIONS
  Combined clopidogrel and aspirin overcome single drug resistances, are safe for bleeding and improve venous graft patency.
authors.affiliation: Department of Cardiac Surgery, University of Naples Federico II, Naples, Italy. vitomannacio2@libero.it
authors.forename: Vito Antonio
authors.initials: VA
authors.lastname: Mannacio
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Tommaso
authors.forename: Anita
authors.initials: A
authors.lastname: Antignan
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Amicis
authors.forename: Carlo
authors.initials: C
authors.lastname: Vosa
mesh_terms: D054058:Acute Coronary Syndrome / Q000000981:diagnostic imaging / Q000601:surgery*; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D000077144:Clopidogrel; D017023:Coronary Angiography; D047549:Coronary Artery Bypass, Off-Pump / Q000379:methods*; D054059:Coronary Occlusion / Q000097:blood / Q000000981:diagnostic imaging / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin