REDUCE-FMR: Percutaneous Annuloplasty Reduces Regurgitation in Heart Failure Patients With Functional MR
Results of the sham-controlled trial show promise for the Carillon system, but experts await the US pivotal trial, which just enrolled its first patient.
SAN DIEGO, CA—Compared with a sham procedure, a new implantable system that targets dilated mitral annuli has been shown to reduce functional mitral regurgitation (MR) substantially in patients with heart failure with no differences in cumulative major adverse events through 1 year, according to the results of the REDUCE-FMR trial.
“The advantage of this technology is that all other options are still open,” said Horst Sievert, MD (CardioVascular Center Frankfurt CVC, Germany), who presented the results today in a late-breaking trial session at TCT 2018. “You can do whatever you want—MitraClip, surgery, mitral valve implantation, even direct annuloplasty techniques. It doesn’t prevent from anything surgically. Everything can be done.”
The Carillon Mitral Contour System (Cardiac Dimensions) is an indirect annuloplasty device that is delivered transjugularly, with a distal anchor implanted in the great cardiac vein and a proximal anchor embedded in the coronary sinus to essentially cinch the mitral annulus. For this phase II study, Sievert and colleagues enrolled 135 heart failure patients with functional MR 2+. Fifteen patients were excluded for mainly anatomical reasons. Eighty-seven patients were treated with the device, while 33 underwent a sham procedure that included sedation, earplugs, groin incision, and coronary and sinus angiograms. Assessors and echocardiographers were completely blinded to all procedures including the timing of the angiograms.
After 12 months, there was no difference in the cumulative major adverse event rates between the study and sham procedure arms (16.1% vs 18.2%). In the intention-to-treat analysis, those who received the Carillon device saw a 22% reduction in regurgitant volume compared with an 8% increase in those who had sham procedures (P = 0.03). Though this benefit was elevated in the as-treated population (P = 0.02), it was not significant in the per-protocol analysis (P = 0.06).
Additionally, trends for positive remodeling with regard to LV end-systolic volume and LV end-diastolic volume were observed on echocardiography in the as-treated analysis.
“This sham-controlled study in FMR patients should inform future clinical research,” Sievert said during his presentation. “Sham-controlled trials in valve therapy can be performed, but careful echo prescreening of patients by a core lab is necessary.”
The sham-controlled US pivotal trial of the Carillon system recently enrolled its first patient and “is powered to a hierarchical endpoint, which includes clinical endpoints,” he added.
Comparisons With COAPT
Ori Ben-Yehuda, MD (Cardiovascular Research Foundation, New York), who led the morning’s media briefing, pointed out that the rates of mild MR in the trial were strikingly lower after assessment than what they were originally diagnosed as.
“The issue with the mild MR patients happened because the core lab was also blinded regarding the timing of the echo,” Sievert explained. “That means nobody during the trial realized we included patients with mild MR. It's unusual to do this, because usually core labs are blinded regarding the patient and the location of the different treatment arms, but usually they are not blinded regarding the timing of the echo.”
Regardless, Jeffrey Popma, MD (Beth Israel Deaconess Medical Center, Boston, MA), congratulated the researchers on the study since “to be able to do a sham-controlled trial now is almost impossible.” With the presentation of COAPT this morning, however, he questioned whether a sham control is really needed, asking: “Can we just make sure that what we have to do is make absolutely certain that the patients are on optimal medical therapy?”
Sievert replied that there are other factors that could be potentially affected, though. “Obviously COAPT cannot be blinded because there's a clip in the way, . . . but I think blinding has advantages beyond the placebo effect,” he said.
“One of the subtle differences here is that in the REDUCE-FMR trial the difference was due to both positive left ventricular remodeling in the treatment arm and continued progression in the sham control arm,” explained panelist Michael Mack, MD (The Heart Hospital Baylor, Plano, TX). “In COAPT, the difference in improvement that we saw in left ventricular function was totally to prevent the progression of the disease. It's not that the treatment [made the patient] better. We just stabilized the disease to where it's at. So that's an interesting difference. Here we were able to demonstrate positive left ventricular remodeling.”
Still, Sievert cautioned, “this was very small numbers and the study was not really powered to find that difference.”
Sievert H. A sham-controlled randomized trial of transcatheter mitral valve indirect annuloplasty in patients with heart failure and secondary mitral regurgitation. Presented at: TCT 2018. September 23, 2018. San Diego, CA.
- Sievert reports receiving other financial support from 4tech Cardio, Abbott, Ablative Solutions, Ancora Heart, Bavaria Medizin Techonologie GmbH, Bioventrix, Boston Scientific, Carag, Celonova, Cibiem, Comed B.V., CVRx, Edwards, Endologix, Hemoteq, Lifetech, Maquet Getinge Group, Medtronic, Mitralign, and Nuomao M.
- Popma reports receiving grant/research support from Abbott Vascular, Abiomed, Boston Scientific, Cook Medical, Edwards Lifesciences, and Medtronic and consultant fees/honoraria/speaker’s bureau fees from Boston Scientific and Edwards Lifesciences.
- Mack reports receiving grant/research support from Abbott Vascular, Medtronic, and Edwards Lifesciences.
- Ben-Yehuda reports no relevant conflicts of interest.