Perioperative aspirin therapy in CABG improves graft patency, prevents ischemic events, and prolongs survival.  However, Aspirin resistance is common after CABG, particularly in the immediate post-operative period, in part due to cardiopulmonary bypass causing a pro-inflammatory, pro-thrombotic state.  Clopidogrel has revolutionised the practice of interventional cardiology but it remains unknown whether more aggressive antiplatelet treatment with aspirin and clopidogrel may be warranted to improve outcomes after CABG.

To examine this question the authors conduct a retrospective analysis of a multi-centre US database and analysed information on 15,067 adults undergoing CABG between 2003 and 2006.  Of these, 3268 (22%) received dual antiplatelet therapy post-operatively.  Compared with aspirin alone, aspirin plus clopidogrel was associated with a reduction in in-hospital mortality (0.95% vs. 1.78%; adjusted odds ratio: 0.50; 95% confidence interval: 0.25, 0.99) although there was no significant difference in ischaemic or thrombotic events to account for this.  Of note, bleeding events were found to be lower in the combined therapy group than in the aspirin alone group (4.19% vs. 5.17%; adjusted odds ratio:0.70; 95% confidence interval: 0.51-0.97), a highly unexpected finding.  In addition, there was no difference in the relative effect of combined treatment between on-pump and off-pump coronary artery bypass grafting suggesting no clinically adverse effect from using cardiopulmonary bypass.

As with all retrospective studies, this analysis is replete with confounders, with no information available regarding reasons for drug initiation, length of treatment, or dose given.  The possibility of selection bias is high, with clopidogrel possibly being given to patients who were perceived to be low risk and so may have had a generally more benign clinical course than their contemporaries regardless of treatment allocation.  However, the findings are in broad agreement with previous similar studies that also found benefits for clopidogrel in the post-operative period and have demonstrated higher rates of graft patency and late loss than aspirin alone.

Conclusions:

Dual antiplatelet therapy with aspirin and clopidogrel appears safe and may be beneficial following either on- or off-pump coronary artery bypass surgery.  However, the results conflict with the findings of the recent CASCADE trial, which found that clopidogrel had  no effect on vein graft intimal hyperplasia.  The need for a sufficiently powered prospective study with hard clinical end-points to answer this pertinent and important issue remains.

•    Kim DH, Daskalakis C, Silvestry SC, Sheth MP, Lee AN, Adams S, Hohmann S, Medvedev S and Whellan DJ.  Aspirin and clopidogrel use in the early postoperative period following on-pump and off-pump coronary artery bypass grafting.  J Thorac Cardiovasc Surg. 2009;138(6):1377-84.

Journals scanned
American Journal of Medicine; American Journal of Physiology: Heart and Circulatory Physiology; Annals of Emergency Medicine; Annals of Thoracic Surgery; Archives of Internal Medicine; BMJ; Chest; European Journal of Cardiothoracic Surgery; JAMA; Journal of Clinical Investigation; Journal of Diabetes and its Complications; Journal of Immunology; Journal of Thoracic and Cardiovascular Surgery; Lancet; Nature Medicine; New England Journal of Medicine; Pharmacoeconomics; Thorax

Reviewers
Dr Alistair C Lindsay, Dr Jonathan Spiro, Dr Hussain Contractor