Mortality with bivalirudin plus a high-dose infusion versus heparin in patients with acute coronary syndrome

Abstract

Abstract Background The use of bivalirudin in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has been downgraded by recent international guidelines. The reason for this downgrade lies above all on the excess of acute stent thrombosis (ST) associated with bivalirudin, but subsequent studies have suggested that a post-PCI high-dose bivalirudin infusion may mitigate the risk of acute ST related to the short half-life of bivalirudin. Methods We performed an updated meta-analysis of RCTs comparing bivalirudin followed by a post-PCI high-dose infusion versus UFH in ACS. Four RCTs accounting for a total of 16,920 patients were included. Odds ratios (OR) with 95% confidence intervals (CIs) using random effect models were calculated. Number needed to treat (NNT) were also calculated. Clinical outcomes at 30 days were included in the analysis. Results Four RCTs accounting for a total of 16,920 patients were included. We found that bivalirudin is associated with a non-significant reduction of 30-day all-cause death (OR 0.81, 95% CI 0.56-1.16, NNT 250, I2 53%), compared with UFH. Results were consistent at a subgroup analysis of STE-ACS versus NSTE-ACS and in a sensitivity analysis excluding the VALIDATE-SWEDEHEART, the only study using a shorter post-PCI bivalirudin infusion (mean 57 min) that was not used in the totality of patients (65%). Moreover, bivalirudin followed by a high-dose infusion was associated with a significant reduction of net adverse clinical events (NACE) (OR 0.62, 95% CI 0.42-0.90, NNT 31, I2 87%) as defined in each trial and of ST (OR 0.47, 95% CI 0.31-0.71, NNT 200, I2 1%), compared with UFH. Finally, BARC 3-5 bleeding was non-significantly reduced (OR 0.36, 95% CI 0.12-1.02, NNT 143, I2 82%) with bivalirudin compared with UFH. Conclusion We conclude that bivalirudin followed by a high-dose infusion is associated with reduced ST and NACE compared with UFH, but whether it may reduce all-cause mortality requires further investigations.