Marlene Busko

May 25, 2017

NEW ORLEANS, LA — Valve type—balloon expandable or non–balloon expandable—did not make a significant difference to the risk of any 30-day major bleeding or cardiovascular events after transcatheter aortic-valve replacement (TAVR) in patients in the BRAVO 3 trial[1], which was primarily a comparison of bivalirudin (Angiomax, the Medicines Company) with unfractionated heparin in TAVR.

On the other hand, there was a hint of a possible advantage in patients with the non–balloon-expandable valves, according to researchers. Those patients, who received larger sheaths and larger valves, may have fared better with bivalirudin.

"But I would caution against extending that as a general statement, because the overall trial results were negative," said Dr Usman Baber (Icahn School of Medicine at Mount Sinai, New York).

"I don't think we have enough justification for use of bivalirudin in the setting of TAVR," he added, in a press briefing at the Society for Cardiovascular Angiography and Interventions (SCAI) 2017 Scientific Sessions.

"Whether or not that's a chance finding or a real finding needs further investigation," Babar reiterated to heartwire from Medscape.

Similarly, in a late-breaking clinical-trial session, coauthor Dr Roxana Mehran (Icahn School of Medicine at Mount Sinai, New York) stressed that the findings are "hypothesis generating."

In the original BRAVO 3 trial, "we thought we should really be able to reduce bleeding in this patient population, [but] we weren't able to show it," she said. In this analysis, "we couldn't show that one valve was more thrombogenic, but we are really underpowered.

"We were not underpowered to look for the bleeding-avoidance strategy of using bivalirudin," however. "That is an important finding, that bivalirudin does not have a place in TAVR at the moment."

"I think the bottom line was they did not see any difference in any of the clinical outcomes looked at depending on the valve type," session comoderator Dr Applegate (Wake Forest Baptist Health, Winston-Salem, North Carolina) told heartwire .

"In my mind this is reassuring to many of the clinicians out there who are using these valves and wondering if there might be a higher likelihood of bleeding with one vs the other."

The study, by Dr Axel Linke (University of Leipzig, Germany) and colleagues, was simultaneously published in Catheterization and Cardiovascular Interventions.

Effect of TAVR Valve, Anticoagulant Choice

Linke and colleagues aimed to compare 30-day outcomes by type of valve—balloon expandable and non–balloon expandable—and anticoagulation—bivalirudin or heparin—in patients in BRAVO 3.

"As you know this is kind of a hot question, because we've never seen valve-vs-valve studies head on," but Mehran reminded the audience that BRAVO 3 was not randomized for valve type, only for anticoagulation type. The operator was free to choose what type of valve to use.

The balloon-expandable valves that were used were Sapien valves (Edward's Lifesciences), mainly the third-generation Sapien XT valve or the newer Sapien 3 valve.

The non–balloon-expandable valves were mainly the self-expanding Medtronic valves (83%), including the third-generation CoreValve and new Evolut R (Medtronic), and less often Portico, Lotus, Symetis Acurate Neo, and Direct Flow valves.  

The study's co–primary outcomes were major bleeding (defined as Bleeding Academic Research Consortium [BARC] ≥3b) at 30 days, and a composite of major adverse cardiovascular events (MACE; all-cause mortality, MI, or stroke) or major bleeding at 30 days.

Of 802 patients enrolled in BRAVO 3 in seven countries in Europe and North America, 500 patients received balloon-expandable valves, 282 patients received non–balloon-expandable valves, and 20 patients had unknown valve type.

There were significant differences between patients who received the two valve types.

Compared with other patients, those who received non–balloon-expandable valves were older (mean age 83 vs 82), weighed less (73 vs 75 kg) and were less likely to have diabetes (25% vs 33%); they also had a higher mean EuroSCORE I (17.9 vs 16.5) and lower mean LVEF (52.5 vs 54.2).

Patients who received non–balloon-expandable valves were less likely to have local anesthesia or require valvuloplasty. Almost all (90%) had a sheath size of at least 18 French and most had valves that were 29 mm or greater.

In contrast, close to 50% of patients who had a balloon-expandable valve had a sheath size of less than 18 French, and 70% had a 23-mm or 26-mm valve.

After the procedure, patients who had had a balloon-expandable valve implanted were also more likely to be receiving a P2Y12 inhibitor and less likely to be receiving an anticoagulant.

At 30 days, patients who had received a non–balloon-expandable valve had nonsignificant increased adjusted odds of all-cause mortality and major vascular complications.

30-Day Post-TAVR Adverse Outcomes, Non–Balloon-Expandable vs Balloon-Expandable Valves

Outcome Adjusted OR (95% CI) P
BARC >3b 1.33 (0.68–2.61) 0.409
MACE 1.69 (0.88–3.22) 0.113
NACE 1.51 (0.91–2.49) 0.108
Major vascular complications 1.78 (0.97–3.26) 0.062
Death 2.07 (0.91–4.70) 0.084
NACE, net adverse cardiac events (MACE or major bleed BARC ≥3b)

Diving deeper, among patients who received non–balloon-expandable valves, those who had anticoagulation with bivalirudin vs heparin had a significantly lower risk of major vascular complications (P interaction=0.039)—"but these are small numbers of patients," Mehran cautioned.

Trial limitations also include possible unmeasured confounders and lack of information on use of implanted permanent pacemakers.

"There may be a potential role for use of bivalirudin in [non–balloon-expandable TAVR], which deserves further investigation," according to Linke and colleagues.

The trial was funded by the Medicines Company. Linke reports no relevant financial relationships. Mehran reported that she received research grants that were paid to her institution from Eli Lilly/Daiichi-Sankyo, Bristol-Myers Squibb, AstraZeneca, the Medicines Company, OrbusNeich, Bayer, CSL Behring, Abbott Laboratories, Watermark Research Partners, Novartis, Medtronic, AUM Cardiovascular, and Beth Israel Deaconess Medical Center. She received consulting and other fees from Janssen Pharmaceuticals, Osprey Medical, Watermark Research Partners, Medscape, the Medicines Company, Boston Scientific, Merck, Cardiovascular Systems, Sanofi, Shanghai BraccoSinePharmaceutical, and AstraZeneca, and she owns stock in Claret Medical and Elixir Medical. Disclosures for the coauthors are listed in the paper.

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