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Transcatheter mitral valve repair's big win for outcomes of functional mitral regurgitation (MR) in heart failure in the COAPT trial left many wondering how it will affect recruitment in future MR trials.

COAPT found fewer hospitalizations for heart failure over 24 months in patients randomized to MitraClip placement in addition to guideline-directed medical therapy relative to those receiving medications alone (35.8% versus 67.9% per patient-year, HR 0.53, 95% CI 0.40-0.70).

It also significantly reduced all-cause mortality, Gregg Stone, MD, of Columbia University Medical Center and the Cardiovascular Research Foundation in New York City, reported at a late-breaker trial session at the Transcatheter Cardiovascular Therapeutics (TCT) conference in San Diego, with simultaneous publication in the .

"The trial has completely changed the paradigm of how we manage these patients," commented Paul Sorajja, MD, of Minneapolis Heart Institute at Abbott Northwestern Hospital. He called MitraClip therapy poised to be "the new standard of care" for heart failure with severe MR and said that future trials will have to consider it in the control arm.

Part of what made the trial so successful was that patients stayed on optimal medical therapy in both MitraClip and control groups.

Offering the FDA point of view was medical officer John Laschinger, MD, who stressed the importance of a heart failure team to direct this appropriate use of guideline-directed medical therapy in future trials. "If there's no compliance, you have no control arm," he said at an FDA town hall session.

"What is the impact of COAPT going to be on recruitment? Is this a rising tide that floats all boats or only one boat?" asked session moderator Michael Mack, MD, of Baylor Scott & White The Heart Hospital – Plano Research Center in Texas.

It will be a "double-edged sword," in the words of panelist Eric Vang, PhD, MPH, of Medtronic: "One thing COAPT will do is encourage people to want about their MR." That said, people won't want to be in a trial where one side is an established treatment and the other side is totally unknown. This makes it "harder for them to choose to be in a trial."

Stone acknowledged that COAPT introduces new challenges but said these challenges can be overcome by industry. "I think it will spur innovation," he said, disagreeing with the notion that trials will necessarily be harder to enroll in the future.

Ultimately, the FDA is "excited" about the trial and believes that the findings "confirm the idea that we need to very rigorously think about how we are designing these trials," said FDA biomedical engineer Jaime Raben.

COAPT included 614 patients with heart failure from the U.S. and Canada who were randomized to medical therapy with or without the MitraClip procedure. Participants had to have left ventricular (LV) ejection fraction in the 20% to 50% range (31.3% was the mean). The cohort was roughly split in having grades 3+ and 4+ MR.

The lower all-cause mortality rate within 24 months with the intervention (29.1% versus 46.1%, HR 0.62, 95% CI 0.46-0.82) mainly emerged more than 1 year after treatment -- a delayed response suggestive of long-term benefits from a durable decrease in the severity of LV volume overload, according to the COAPT researchers.

Their trial came just after MITRA-FR investigators reported no benefit to mitral valve repair in a similar patient population.

MitraClip is currently FDA-approved only for primary MR among those at prohibitive risk for surgery.

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