Abstract 3297: The Impact of Renal Dysfunction on Bleeding and Outcome in ST-Elevation MI: Results of the ExTRACT-TIMI25 Study
Although severe renal dysfunction (creatinine clearance, CrCl< 30ml/min) is associated with increased risk of adverse events and the requirement for dose adjustment of anti-thrombotics, it is unclear whether more subtle degrees of renal dysfunction impact on the rate of clinical events. In the ExTRACT-TIMI 25 trial 20,479 patients with ST elevation MI were randomized to enoxaparin (ENOX) or UFH, together with fibrinolytic therapy. As previously reported the primary end point (death/non fatal MI at 30 days) occurred in 12.0% of UFH patients vs 9.9% ENOX (p<0.001). Major bleeding at 30 days occurred in 1.4% UFH and 2.1% ENOX (p<0.001). Outcome events and bleeding were analysed according to strata of CrCl. By logistic regression a 10ml/min decrease in CrCl conferred an increased risk of death (OR 1.34, p<0.001) and death/non fatal MI at 30 days (OR 1.20, p<0.001). CrCl remains an independent predictor having adjusted for baseline characteristics. Comparing UFH with ENOX, rates of death/MI at 30 days were similar for CrCl<30 (37.7 vs 33.0), CrCl 30 – 60 (19.4 vs 19.4 respectively). However for lesser degrees of renal dysfunction ENOX was significantly superior: CrCl 60–90 (12.1 vs 9.6, p<0.001) and CrCl > 90 (7.3 vs 5.1, p<0.001). Major bleeding was similar in the 2 treatment groups for CrCl >90, but with increasing renal dysfunction excess bleeding was seen with ENOX.
For ALL patients there is an increase in clinical events and bleeding even with modest degrees of renal dysfunction.
There is a progressive increase in risk of bleeding with ENOX as renal function worsens.
There is a progressive increase in the treatment benefit with ENOX in patients with better renal function.