BRAVO 3: Bivalirudin Similar to Heparin in Transfemoral TAVR

In patients with severe symptomatic aortic stenosis undergoing transfemoral transcatheter aortic valve replacement (TAVR), procedural anticoagulation with bivalirudin performs as well as but no better than heparin at reducing major bleeding or adverse cardiac events, according to late-breaking data presented at TCT 2015 and simultaneously published in the Journal of the American College of Cardiology. 

For the BRAVO 3 trial, Thierry Lefèvre, MD, of Hopital Privé Jacque Cartier, Massy, France, and colleagues randomized 802 high-risk patients (mean age 82.3 years; 48.8% women) undergoing transfemoral TAVR at 31 sites in seven countries to treatment with bivalirudin (bolus 0.75 mg/kg plus continuous IV infusion at 1.75 or 1.4 or 1 mg/kg/h, depending on renal function; n = 404; Angiomax, The Medicines Company) or a weight-adjusted bolus of unfractionated heparin (n = 398).

Procedural success exceeded 97% in each cohort and balloon-expandable devices were used in about two-thirds of patients.

Noninferior endpoints

Noninferiority, but not superiority, criteria were met for bivalirudin vs. heparin therapy with regard to the co-primary endpoints of major bleeding (BARC ≥ 3B) at 48 hours and net adverse CV events (NACE; death, MI, stroke, and major bleeding) at 30 days (Figure).

At 48 hours, there was a trend toward increased NACE with heparin vs. bivalirudin (12.6% vs. 8.9%; P = .09). There were no instances of MI in the bivalirudin group within 48 hours and five in the heparin arm (P = .03). However, acute kidney injury was more likely within 48 hours in the bivalirudin group (10.9% vs. 6.5%; P = .03). There were no differences in major vascular complications or new onset atrial fibrillation.

At 30 days, there was no longer a difference in MI or acute kidney injury between the study arms.

 “Despite not achieving superiority, noninferiority was met and no safety concern was identified,” Lefèvre said. “Bivalirudin can be the alternative anticoagulant during TAVR in patients who cannot be treated with heparin.”

‘The field has changed’

When the study was designed, major bleeding was a bigger hazard with TAVR procedures and often contributed to higher mortality, said TCT Course Director Martin B. Leon, MD, of NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, N.Y.

“But the field has changed,” he said, mentioning that more procedures are now done transfemorally and with smaller sheaths. The power of BRAVO 3 “reflected an earlier time,” Leon continued, and that was likely responsible for the lack of outcomes differences observed in the study.

An interesting finding, Leon said, “is that [the researchers] did demonstrate that bivalirudin is safe” in high-risk TAVR patients, eliminating prior concern for its use in patients who, for whatever reason, are not good candidates for heparin.

Going forward, session co-moderator Jeffrey J. Popma, MD, of Beth Israel Deaconess Medical Center, Newton, Mass., said the question of anticoagulation will have to be addressed.

“The usefulness of dual antiplatelet therapy right now has been heavily questioned, and it’s very controversial,” Leon added. “I don’t think there are any data suggesting that it has incremental benefit over a single agent. There are absolutely no data to suggest that duration of therapy makes a difference in terms of any of the clinical outcomes we look at. It’s a fertile area now for investigation but a difficult one to investigate as well.”

Disclosures:

• Lefèvre reports multiple conflicts of interest with Boston Scientific, Direct Flow Medical, Edwards Lifesciences, Medtronic and Symetis. 
• Leon reports receiving grant/research support from Abbott Vascular, Bard Medical, Edwards Lifesciences, Medtronic and St. Jude Medical; consultant fees/honoraria/speaker’s fees from Abbott Vascular, Boston Scientific, Medtronic, and St. Jude Medical; and holding equity in Claret, Coherex Medical, Elixir, Guided delivery systems, Medinol, Mitralign and Valve Medical. 
• Popma reports receiving grant/research support from Abbott Vascular, Boston Scientific, Cook Medical and Medtronic; consultant fees/honoraria/speaker’s fees from Abbott Vascular, Boston Scientific and Direct Flow Medical; and holding equity in Direct Flow Medical.