Results inform management of severe aortic stenosis

RECOVERY, FRANCE-TAVI, GALILEO and GALILEO-4D   

Researchers in Late-Breaking Science sessions during Scientific Sessions in Philadelphia presented the latest findings on:

  • Optimal timing of surgery for asymptomatic severe aortic stenosis
  • Best prosthetic valve design
  • Whether anticoagulation is efficacious and safe for patients after TAVR without indication for anticoagulation

Early surgery may be effective for asymptomatic severe aortic stenosis

Early aortic valve replacement may be effective in asymptomatic patients with asymptomatic severe aortic stenosis, according to the Randomized Comparison of Early Surgery Versus Conventional Treatment in Very Severe Aortic Stenosis (RECOVERY) trial.

The study randomized 145 patients with severe AS to early surgery or conventional management. In an intention-to-treat analysis including all study patients, one of 73 patients assigned to early surgery and 11 of 72 patients assigned to conventional treatment died from cardiovascular causes.

Five deaths from any cause occurred in the early surgery group and 15 in the conventional-management group. The cumulative incidence of the primary endpoint (operative mortality or cardiovascular mortality) was 1.4% at eight years in the early-surgery group, compared with 25.5% at eight years in the conservative-management group (P=0.003). The cumulative incidence of death from any cause was also lower in the early surgery group than in the conservative-management group.

“Our randomized trial provides the evidence to support early pre-emptive aortic valve replacement in asymptomatic patients with very severe aortic stenosis,” said Duk-Hyun Kang, MD, PhD, professor of medicine in the Division of Cardiology of Asan Medical Center in Seoul, Korea.

Balloon-expandable valves associated with less risk of PVR, mortality

A balloon-expandable valve may be superior to a self-expandable one for AS patients receiving TAVR, according to results from the FRANCE-TAVI registry.

Both valve designs are used in patients with AS undergoing TAVR/TAVI.

FRANCE-TAVI is the largest observational trial to date to compare the two valve designs head to head with the risk for paravalvular regurgitation and in-hospital mortality as a co-primary endpoint.

Enrollment included 12,141 patients with native aortic stenosis undergoing TAVI from 2013 to 2015. Among them, 3,910 patients were treated with balloon-expandable valves and 3,910 patients with self-expandable valves.

Self-expandable valve recipients had higher risks of a combined endpoint of moderate to severe paravalvular regurgitation and in-hospital mortality and a greater likelihood of two-year mortality compared to patients who received balloon-expandable valves.

Patients with moderate to severe PVR had a 40% higher risk of death by two years.

“The next step is to conduct a large prospective randomized trial comparing the current generation of the two valve designs,” said Eric Van Belle, an interventional cardiologist and head of the Lille Heart and Lung Institute at Regional University Hospital in France, and the study’s principal investigator.

GALILEO, GALILEO-4D reveal need for trials for TAVR patients not requiring anticoagulation

Early observational imaging studies suggest that after successful TAVR, patients without an established indication for oral anticoagulation may be at increased risk for stroke and subclinical valve leaflet thrombosis.

The Global Comparison of a Rivaroxaban-Based Antithrombotic Strategy Versus an Antiplatelet Strategy After Transcatheter Aortic Valve Replacement (GALILEO) is a phase III, global, multicenter, randomized-controlled trial to evaluate the efficacy and safety of daily rivaroxaban-based antithrombotic therapy versus antiplatelet-based therapy in reducing death and thromboembolic events after successful TAVR in patients without an established indication for oral anticoagulation.

Participants included 1,644 patients who were enrolled after successful TAVR if they had no atrial fibrillation or other indication to receive ongoing anticoagulation.

Patients were treated with 10 mg rivaroxaban once daily, plus 75 mg to 100 mg aspirin once daily for 90 days. That was followed by rivaroxaban alone or an antiplatelet strategy: 75 mg clopidogrel plus 75 mg to 100 mg aspirin once daily for 90 days followed by aspirin alone.

“Of note, 10 mg dose of rivaroxaban is lower and reasonably expected to have less bleeding side effects than the 15 to 20 mg routinely indicated for stroke prevention in atrial fibrillation,” said George Dangas, MD, PhD, senior investigator and director of Cardiovascular Innovation at the Zena and Michael A. Wiener Cardiovascular Institute at Mount Sinai Hospital in New York City.

However, the rivaroxaban arm had higher rates of death or thromboembolic complications and more bleeding complications. The mechanism underlying the higher mortality in the rivaroxaban arm observed in the trial remains unclear.

The GALILEO was stopped in August 2018, after the DSMB recommended halting the trial when analysis suggested harm. The final data, submitted to the New England Journal of Medicine in September 2019, track with the preliminary safety data.

“Our study results indicate that the use of anticoagulation after TAVR is not useful at all in patients who do not have any specific indication for such treatment,” Dangas said.

Conversely, in GALILEO-4D, a CT-scan substudy of GALILEO involving 231 patients, rivaroxaban decreased subclinical valve leaflet thrombosis to a substantial degree compared to treatment with an antiplatelet in patients with no indication for chronic coagulation.

The primary endpoint was the proportion of patients with at least one bioprosthetic valve leaflet with more or equal to 50% valve motion reduction. Cardiac four-dimensional computed tomography detected the phenomenon.

The primary endpoint was found in 11 patients (10.9%) in the antiplatelet arm versus only two patients in the rivaroxaban arm (2.1%). Overall, researchers found subclinical leaf thickening on at least one prosthetic valve leaflet in 12.4% in the rivaroxaban arm versus 32.4% in the antiplatelet arm.

“This specific anti-thrombotic treatment as investigated in GALILEO-4D helped prevent subclinical leaflet thickening and reduced leaflet motion, but the data have to be interpreted cautiously and carefully within the context of the main GALILEO trial,” said Ole De Backer, MD, PhD, an interventional cardiologist at Rigshospitalet University Hospital in Copenhagen, Denmark, and the study’s lead investigator.

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