Risk of Stent Thrombosis and Major Bleeding with Bivalirudin Compared with Active Control: A Systematic Review and Meta-analysis of Randomized Trials

- Safety/ efficacy of bivalirudin, a common anticoagulant, was recently questioned.
- We studied randomized trials of bivalirudin vs active control in the setting of PCI.
- Bivalirudin is associated with reduced risk of bleeding, but increased thrombosis.
- Results are consistent across most analyses and clinical subgroups.
- Widespread use of bivalirudin in PCI might need to be reconsidered.

BackgroundBivalirudin is commonly used for patients undergoing percutaneous coronary intervention (PCI), but there have been recent concerns that it may be associated with an increased risk of stent thrombosis and provide no benefit regarding major bleeding compared with active control.Methods and ResultsWe searched PubMed, clinicaltrials.gov, and conference proceedings for randomized controlled trials of bivalirudin versus active control in patients undergoing PCI. The main outcomes of interest were definite stent thrombosis, myocardial infarction, major bleeding, and mortality. We used random-effects modeling to pool the data. We included 25 trials involving 41,243 patients. Overall, use of bivalirudin compared with active control was associated with an increased risk of definite stent thrombosis (11 trials; 16,864 patients; RR, 1.73; 95% CI, 1.24-2.40; P < 0.001; I2 = 0%), similar risk of acute myocardial infarction (22 trials; 40,578 patients; RR, 1.00; 95% CI, 0.87-1.16; P = 0.96; I2 = 43%), decreased risk of major bleeding (25 trials; 41,243 patients; RR, 0.59; 95% CI, 0.49-0.72; P < 0.001; I2 = 31%) and of cardiac death (6 trials; 6,956 patients; RR, 0.72; 95% CI, 0.53-0.99; P = 0.05; I2 = 0%), but no change in all-cause mortality (24 trials; 41,058 patients; RR, 0.96; 95% CI, 0.81-1.15; P = 0.69; I2 = 0%). Results were consistent across a wide set of subgroup and sensitivity analyses.ConclusionsCompared with active control, bivalirudin is associated with increased risk of stent thrombosis but lower risk of major bleeding, with no discernible impact on all-cause mortality.