Heart 98:1710-1715 doi:10.1136/heartjnl-2012-302449
  • Original articles
    • Cardiovascular surgery

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

  1. Carlo Vosa1
  1. 1Department of Cardiac Surgery, University of Naples Federico II, Naples, Italy
  2. 2Department of Cardiology, Azienda Ospedaliera Santobono-Pausillipon, Naples, Italy
  1. Correspondence to Dr Vito Antonio Mannacio, Via S Domenico 62, 80127 Naples, Italy; vitomannacio2{at}
  1. Contributors VAM conceived the study, acted as principal investigator and led the protocol development, study implementation, interpretation of data and report writing. LDT contributed to protocol development and study implementation including a special contribution to interpretation of data. AA acted as the data manager and contributed to data collection, interpretation of the results and revised the report. VDA contributed to data collection and management and revised the report. CV directed the development of the study and revised it critically for important intellectual content. All authors have given final approval of the submitted manuscript. VAM is responsible for the overall content as guarantor.

  • Accepted 24 July 2012
  • Published Online First 2 September 2012


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.

Design 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.

Setting University medical school in Italy.

Patients 300 patients who underwent off-pump coronary artery bypass grafting were randomised to receive aspirin (n=150) or aspirin plus clopidogrel (n=150).

Intervention 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.

Main outcome measures 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.


  • Competing interests None.

  • Ethics approval The study was approved by the ethics committee of the Federico II University Medical School of Naples and the hospital's Institutional Review Board. The presented data are anonymised and there is no risk of identification.

  • Patient consent Written consent was obtained from each patient.

  • Provenance and peer review Not commissioned; externally peer reviewed.