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SAN DIEGO -- Percutaneous repair of the mitral valve improved key outcomes in moderate-to-severe, symptomatic mitral regurgitation for heart failure patients who had exhausted pharmaceutical options, the COAPT trial showed.

The primary efficacy endpoint of heart failure hospitalizations within 24 months fell a relative 47% with MitraClip implantation compared with medical therapy alone (annualized rate 35.8% vs 67.9%, P<0.001), reported Gregg Stone, MD, of Columbia University Medical Center in New York City, at the Transcatheter Cardiovascular Therapeutics conference.

All-cause mortality at 24 months was also substantially reduced to 29.1% versus 46.1% among controls (HR 0.62, P<0.001).

The number needed to treat was 3.1 to prevent a heart failure hospitalization within 24 months and 5.9 to save one life within 24 months.

The findings, simultaneously published in the New England Journal of Medicine, follow closely on the heels of the MITRA-FR trial, which showed MitraClip did not improve 12-month all-cause mortality and unplanned heart failure hospitalization compared with medical therapy alone (54.6% vs 51.3%, P=0.53).

But both trials concurred on safety of the procedure. In COAPT, the primary safety endpoint of freedom from device-related complications at 12 months (96.6%) met the performance goal. In MITRA-FR, there was a 3.5% rate of complications requiring surgery or transfusion.

"These patients have a very bad prognosis, despite all our best medical therapies, revascularization, and CRT [cardiac resynchronization therapy]," Stone told 乌鸦传媒.

The new data "I believe have very clear implications for the future treatment of patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation -- according to the American Society of Echocardiography criteria -- who remain symptomatic having failed all guideline-directed medical therapy and CRT," he said. "For such patients, the MitraClip should be the standard of care."

COAPT Reigns

"This in a lot of way in my mind trumps the neutrality of results that MITRAL-FR had," commented Vinod Thourani, MD, of MedStar Heart and Vascular Institute in Washington. "This study is a landmark study that will change the management of a very high-risk patient population that, thus far, we have had very few options [for treatment], so that makes it a very attractive therapy."

"The differences were not 2% or 3% or even equivocal. It was a major difference in [heart failure] admission and mortality. We're talking about massively different studies; the results weren't even close to being in the same ballpark," Thourani added.

However, Sanjay Kaul, MD, of Cedars-Sinai Medical Center in Los Angeles, expressed some skepticism at seeing such an "unexpected and unprecedented" mortality boost.

"There are several examples where implausibly large treatment effects seen in small trials fail to be replicated in subsequent investigations," he told 乌鸦传媒. "So the major challenge is how do we reconcile the disparate results of these two trials? ... Luckily, there are two additional trials, RESHAPE and MATTERHORN, which will serve as a tie-breaker. The trials are currently ongoing and will report the results soon (at least RESHAPE). If the results are positive, then we have to acknowledge the COAPT trial results are indeed not 'too good to be true,' and that the trial provides reliable and credible evidence to inform guidelines and guide clinical practice."

Thourani said he didn't see any need for a tie-breaker. "The results are so compelling in the U.S. study that it would shock me if this is not approved for secondary mitral regurgitation in the U.S. [by the] FDA. This study is analogous to the PARTNER IB where we had medical therapy versus [stenting of] severe aortic stenosis, the difference is almost similar to that for difference in outcomes."

Differences in the Trials

As to why the two trials might have come to such different conclusions, leading cardiologists gave a range of explanations.

According to Stone: COAPT with 614 patients was twice the size of MITRAL-FR (n=307); it used the more stringent U.S. criteria for severity of mitral regurgitation, with an effective regurgitant orifice of 31 mm² to MITRAL-FR's 41 mm²; less dilated left ventricles than in MITRA-FR; a more rigorous assurance that patients really had maxed out what optimal medical therapy could do before randomization; over 2 years of follow-up versus 1 year in MITRA-FR; and potentially greater experience with MitraClip among operators.

"Given the size of COAPT and its robustness, these data are definitive to me," Stone told 乌鸦传媒.

Patrick O'Gara, MD, of the Brigham and Women's Hospital in Boston and a past president of the American College of Cardiology, agreed.

"I think that the community of cardiovascular clinicians and surgeons is really desperate for some kind of an intervention that is going to help this very sick population of patients and here's a potential solution," he said in an interview. "So you have a safe, reasonably effective, not very complicated intervention that seems to be associated with significant reductions in heart failure hospitalizations and also all-cause mortality. It's going to be hard to not embrace that."

For U.S. practice, the U.S. data is likely to "carry a lot more weight" than that from France in MITRA-FR, Thourani suggested.

Stone noted that in Europe, and most other places where MitraClip is available, its most common use is in secondary mitral regurgitation -- until now based on data from uncontrolled registry studies -- so the potential for expanding use of the device is huge.

But O'Gara added, "The challenge for us in the United States with respect to how this technology is going to be disseminated is going to, once again, rely on patient selection and making sure we abide by the principles of failure of medical therapy before activating a plan for treatment of mitral regurgitation. That is not always done."

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