EComment. Impact of clopidogrel on bleeding complications and survival in off-pump coronary artery bypass grafting

Abstract

Bittner et al. [1] provide interesting data with regard to clopidogrel and Aprotinin use and long-term survival post coronary artery bypass graft (CABG). A number of issues however need to be addressed prior to adopting their recommendations. Firstly identification of Aprotinin as a potentially harmful agent was delayed due to the large number of inadequately powered studies confirming its effects on reducing blood loss, but inadequately powered with regard to complications and long-term survival [2]. Any study utilising 213 Aprotinin treated patients in two limbs is underpowered, and risks repeating previous mistakes. Secondly univariate analysis of survival (Kaplan-Meier) is statistically unsafe in situations where numerous significant factors determine long-term survival, hence the technique of Cox regression analysis. As Bittner has not adjusted for any significant confounding variables the conclusions drawn are potentially incorrect. We have recently described [3] age, diabetes, left ventricle function, body mass index, peripheral vascular disease, dialysis, left internal mammary artery (LIMA) usage, EuroSCORE, and creatinine kinase muscle-brain isotype (CKMB) as factors that would need to be included in the Cox analysis. The risk survival figure obtained would then need to be plotted at the mean of the covariates to assess the effect of clopidogrel. Thirdly from their analysis it is impossible to separate the timing of stopping of clopidogrel and its use post operatively, on the benefit on long term survival. Assessment of platelet function pre operatively may enable an 'optimum' platelet inhibition range to be identified where the rate of bleeding and blood product utilisation is at a minimum and long-term survival is at a maximum. In addition the dose and anti platelet effect of aspirin was not mentioned in the manuscript. Fourthly recommending Aprotinin usage would seem incongruent with their data as the combined clopidogrel Aprotinin group had the worst long-term survival of 79.7% compared to clopidogrel alone 93.8%. Lastly, no studies exist as to the beneficial effect of blood transfusion on long term survival, in the absence of catastrophic haemorrhage [4]. This makes the recommendation of a technique that increases transfusion requirements as a ‘high risk approach’. Adopting a surgical strategy that involves increased blood product administration and the utilisation of Aprotinin seems intuitively incorrect, however adequately powered and analysed studies are needed. Conflict of Interest: None declared