Results from the COAPT study continue to roll in, and it was all positive news for the MitraClip team at the Transcatheter Cardiovascular Therapeutics (TCT) conference in San Francisco this month.
It’s been three years since the COAPT trial first kicked off, and Abbott’s MitraClip is situated to be a potentially life-changing therapy for patients with severe secondary mitral regurgitation (MR). Two-year results from the study, presented at TCT 2018 in San Diego, were unprecedented—compared to heart failure patients who were treated with guideline-directed medical therapy (GDMT) alone, those randomized to GDMT plus treatment with the MitraClip saw a 47% reduction in HF hospitalizations and a 38% reduction in mortality.
“It just knocks you off your chair how positive this is,” Jeffrey Pompa, MD, of Beth Israel Deaconess Medical Center in Boston, said at the time. Other experts called the research “seminal” and said they regarded COAPT as a “blockbuster trial” in the field.
But three-year results from the study are “even more dramatic” than their predecessors, co-investigator Michael J. Mack, MD, the medical director of cardiovascular surgery at Baylor Scott and White in Dallas, said at TCT 2019. While 66.6% of patients randomized to GDMT alone and 44.5% of patients randomized to GDMT plus MitraClip therapy met COAPT’s primary endpoint of death or HF hospitalization at two years, 88.1% and 58.8%, respectively, met the endpoint at three years. That’s an absolute benefit of 30% with the MitraClip.
The team’s other metrics were similarly positive, Mack said. The number of patients needed to treat to prevent death or HF hospitalization at two years was 4.5 at 24 months, but at 36 months that number fell to 3.4.
“This same curve holds true for heart failure hospitalizations, time to first heart failure hospitalization, death, or death and heart failure hospitalization,” Mack said.
Crossovers take center stage
As exciting as the team’s three-year findings were, a TCT press conference centered around one of the more novel aspects of this year’s results: crossover data. COAPT originally randomized 302 secondary MR patients to GDMT plus the MitraClip and 312 patients to the GDMT-only control arm, and the latter group wasn’t allowed to cross over to the MitraClip until two years into the study.
Of the 312-patient control group, 169 patients were considered ineligible for crossover at 24 months, but 138 were eligible. Thirty-eight percent of that group—58 patients in all—actually crossed over to the MitraClip at two years and saw far more favorable outcomes than their peers who didn’t cross over. At the conference, co-investigator Gregg W. Stone, MD, of New York-Presbytarian Hospital and Columbia University Medical Center, admitted his team was unsure why 62% of patients opted not to switch.
“We don’t know,” he said, noting the device was supplied to all study participants at no cost. “It was offered to everybody, but I do think it was a combination. It was the fact that some were too sick but others were doing, you know, quite well, so they didn’t feel there was a reason to cross over. And others, probably there was somewhat less awareness that this was an opportunity.”
One reporter asked, given MitraClip’s success in crossover patients, whether it was ethical for investigators with the MITRA-FR study to withhold that possibility from their participants for five years. MITRA-FR, which is based in France and enrolled patients with less severe MR and more dilated left ventricles, has seen poorer outcomes and greater procedural complications than COAPT, and restricted its control group to GDMT alone for at least five years.
“The MITRA-FR patients were a very different patient population and did not show any collective benefit—not immediately, not at one year, not at two years,” Stone said. “Now I’m sure, within that population, there are some that might be COAPT eligible.
“If there were some patients, probably 10% or 20%, that would meet the COAPT eligibility criteria, I would strongly recommend that they get treated. But I suspect that it’s a minority of patients.”