Meta-analysis indicates that bivalirudin does increase risk of early stent thrombosis

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Raffaele Piccolo (Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy) and others report in Thrombosis and Haemostasis that, according to the results of a new meta-analysis, bivalirudin (Angiomax, The Medicines Company) significantly increases the risk of early stent thrombosis (specifically, acute stent thrombosis) in patients undergoing percutaneous coronary intervention (PCI) compared with other antithrombotic therapies. However, the drug is also associated with a significant decrease in major bleeding and does not increase the risk of death or myocardial infarction.

Piccolo et al report that while previous studies have raised concerns that bivalirudin increases the risk of early stent thrombosis in patients undergoing PCI, none of the available randomised trials have been “adequately powered to allow a reliable estimation of such a rare event [ie. stent thrombosis]”. Therefore, they “sought to perform a meta-analysis of randomised trials to assess the risk of early stent thrombosis associated with bivalirudin as compared with other antithrombotic regimens in patients undergoing PCI”.

The authors identified 11 studies—including EUROMAX, HORIZONS-AMI, and HEAT PPCI—that compared bivalirudin with heparin, which provided data for 16,415 patients (of whom, 49% were randomised to bivalirudin and 51% were randomised to control antithrombotic regimens). The primary endpoint was definite early stent thrombosis, with secondary endpoints including all-cause mortality, myocardial infarction, and major bleeding.

The risk of early definite stent thrombosis was significantly higher in patients treated with bivalirudin—1.23% vs. 0.66% for patients treated with control antithrombotic therapies (ie. heparin; p=0.00007).  Piccolo et al note: “The excess of early stent thrombosis was 5.2 per 1,000 treated patients, while the number needed to harm was 193”. They add that the increased risk of early stent thrombosis was driven by an increased risk of acute stent thrombosis with bivalirudin (p

This increased risk of early stent thrombosis with bivalirudin did not appear to be associated with an increased risk of death or an increased risk of myocardial infarction as there were no significant differences between the drug and control therapies in either of these endpoints. However, according to the authors, the lack of statistical significance difference in the rates of death or myocardial infarction between groups should be “interpreted with caution”. They explain that the reduction in major bleeding that was observed with bivalirudin (3.17% vs. 5% for the control therapies; p=0.0003) in the study may have “offset the higher risk of reinfarction due to excess of stent thrombosis” with the drug because “major bleeds are also associated with ischaemic events.”

Piccolo et al conclude: “In the absence of a valid therapeutic approach for minimising the risk of early stent thrombosis, the risk of bleeding should be carefully weighed against the risk of stent thrombosis when bivalirudin is used in patients at high risk of thrombotic events.”