SAN FRANCISCO – During transcatheter aortic valve replacement (TAVR), rates of 48-hour major bleeding and 30-day net adverse clinical events (NACE) were similar between patients receiving bivalirudin compared with those who received heparin.

Thierry Lefèvre, MD, of the Institut Hospitalier Jacques Cartier in Massy, France, presented the results of the phase 3b, open label, randomized BRAVO 3 study at the 2015 Transcatheter Cardiovascular Therapeutics annual meeting in San Francisco.

According to Lefèvre, bivalirudin (Angiomax, The Medicines Company, Zurich, Switzerland) is a reversible direct thrombin inhibitor with a half-life of 25 minutes. Although the drug has been shown to reduce major bleeding during percutaneous coronary intervention (PCI) compared with other regimens, its safety and efficacy vs unfractionated heparin in TAVR is unknown.


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In all, 803 high-risk patients from 7 countries and 31 sites underwent TAVR and were randomly assigned 1:1 to receive either bivalirudin or unfractionated heparin.

The co-primary endpoints were BARC ≥3b major bleeding at 48 hours or hospital discharge (whichever came first), and 30-day NACE, defined as a composite of death, myocardial infarction, stroke and major bleeding.

Intent-to-treat analysis results revealed that major bleeding at 48 hours did not significantly differ between the groups (bivalirudin, 6.9% vs. heparin, 9%; P=.27), nor did 30-day NACE (bivalirudin, 14.4% vs. heparin, 16.1%; P=.5).

“Major bleeding and NACE [were] lower than expected in both arms in contemporary transfemoral TAVR,” Lefèvre said during a TCT press conference.

In addition, mortality at 48 hours, a secondary endpoint, was similar between groups (bivalirudin, 1.5% vs. heparin, 1.8%; P=.76).

“Procedural anticoagulation with bivalirudin did not significantly reduce major bleeding at 48 hours or NACE at 30 days compared with heparin,” Lefèvre concluded at a press conference. “Bivalirudin may be the alternative to heparin during TAVR in patients who cannot be treated with heparin.”

In terms of the possible implications of these results for use of bivalirudin in PCI patients, Ajay J. Kirtane, MD, SM, panel moderator from the New York-Presbyterian Hospital/Columbia University Medical Center in New York, NY, said that one of the reasons this study is exciting is because there has been a hypothesis that bivalirudin could reduce bleeding compared with heparin alone in PCI patients.

“While this is a much bigger access site, you don’t necessarily see these trends,” Kirtane said during a press conference. “On the other hand, when you have a bigger access site, there is the potential for an increased signal. But this study is still somewhat underpowered.”

Kirtane added, however, that there is a difference with BRAVO 3 and the studies comparing bivalirudin vs heparin in PCI patients, since no glycoprotein IIb/IIIa inhibitors were used in this study.

Disclosures: This study was funded by The Medicines Company (Zurich, Switzerland). Dr. George D. Dangas has received grants from The Medicines Company (Zurich, Switzerland).

References

1. Dangas GD et al. J Am Coll Cardiol. 2015; doi:10.1016/j.jacc.2015.10.003.

2. Lefèvre T et al. Late-Breaking Trials and First Report Investigations IV. Presented at: 27th Annual Transcatheter Cardiovascular Therapeutics scientific symposium; October 10-15, 2015; San Francisco.