Effect of Bivalirudin on Aortic Valve Intervention Outcomes-3 - BRAVO-3

Jul 19, 2016
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Presenter/Author:
George D. Dangas, MD, PhD, MACC
Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
The Medicines Company
Date Presented:
10/15/2015
Date Published:
05/18/2016
Original Posted Date:
07/19/2016
References

Description:

The goal of the trial was to assess the safety and efficacy of bivalirudin as the anticoagulant for transcatheter aortic valve replacement (TAVR) procedures compared with unfractionated heparin (UFH).

Contribution to the Literature: The BRAVO-3 trial showed that bivalirudin is not superior to UFH as the anticoagulant of choice for transfemoral TAVR procedures.

Study Design

Patients undergoing transfemoral TAVR were randomized in a 1:1 fashion to either bivalirudin (n = 404) or UFH (n = 398). Bivalirudin was administered as a bolus 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h if glomerular filtration rate was ≥60 ml/min. Heparin dosing and administration included a recommended target activated clotting time of >250 seconds; the decision for reversal with protamine at the end of the procedure was subject to standard local institution practice.

  • Total number of enrollees: 802
  • Duration of follow-up: 30 days
  • Mean patient age: 82.3 years
  • Percentage female: 49%

Other salient features/characteristics:

  • Logistic EuroSCORE: 17
  • Prior atrial fibrillation: 37%
  • Prior P2Y12 inhibitor: 31%
  • Balloon-expandable valve: 64%

Inclusion criteria:

  • Severe aortic stenosis
  • Age 18 years of age and older
  • High surgical risk (defined as a EuroSCORE of 18 or over, or deemed inoperable)
  • Scheduled for TAVR via transfemoral access

Exclusion criteria:

  • Planned surgical cutdown access
  • Presence of a previous mechanical or mitral bioprosthetic valve
  • Severe left ventricular dysfunction (ejection fraction <15%)
  • Minimal luminal diameter <6.5 mm for the common femoral artery
  • Severe aortic or mitral regurgitation
  • Concurrent percutaneous coronary intervention (PCI)
  • Recent bleeding or neurologic event
  • Dialysis-dependent patients
  • International normalized ratio (INR) ≥2 on day of TAVR or known history of bleeding diathesis
  • History of hemorrhagic stroke, intracranial hemorrhage, intracerebral mass or aneurysm, or arteriovenous malformation
  • Acute myocardial infarction, major surgery, or any therapeutic cardiac procedure (other than bicuspid aortic valve) within 30 days
  • PCI within 30 days
  • Upper gastrointestinal or gastric ulcer bleed within 30 days

Principal Findings:

  • Co-primary endpoints: Major bleeding (Bleeding Academic Research Consortium [BARC] ≥3b) for bivalirudin vs. UFH at 48 hours: 6.9% vs. 9.0%, p = 0.27
  • Net adverse cardiovascular events at 30 days: 14.4% vs. 16.1%, p for noninferiority < 0.01, p for superiority = 0.5

Secondary outcomes:

  • 48-hour mortality: 1.5% vs. 1.8%, p = 0.76
  • Minor bleeding: BARC 3a: 15.6% vs. 13.3%, p = 0.36; BARC 1 and 2: 20.8% vs. 21.1%, p = 0.91
  • 48-hour stroke: 2.0% vs. 2.0%, p = 0.98

Subset with magnetic resonance imaging (MRI) (n = 60):

  • No difference between bivalirudin vs. heparin for ≥1 new cerebral embolus on MRI (65.5% vs. 58.1%, p = 0.55)
  • Clinical event rates were also similar

Interpretation:

The results of this trial indicate that bivalirudin is not superior to UFH as the anticoagulant of choice for transfemoral TAVR procedures. Cerebral embolization is a common occurrence, but is not reduced by bivalirudin compared with heparin.There is also no significant difference in bleeding events or in adverse cardiovascular events at 48 hours and 30 days. Given the higher cost associated with bivalirudin use, UFH should remain the primary anticoagulant for TAVR procedures.

References:

Van Belle E, Hengstenberg C, Lefevre T, et al. Cerebral Embolization During Transcatheter Aortic Valve Replacement: The BRAVO-3 MRI Study. J Am Coll Cardiol 2016;May 18:[Epub ahead of print].

Dangas GD, Lefèvre T, Kupatt C, et al. Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement: The Randomized BRAVO-3 Trial. J Am Coll Cardiol 2015;66:2860-8.

Presented by Dr. George Dangas at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2015), San Francisco, CA, October 15, 2015.

Keywords: Anticoagulants, Aortic Valve Stenosis, Heparin, Hirudins, Peptide Fragments, Protamines, Stroke, Transcatheter Aortic Valve Replacement, Transcatheter Cardiovascular Therapeutics


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