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SAN FRANCISCO -- The first results out of the U.S. pivotal trial for Medtronic's CoreValve prosthesis for transcatheter aortic valve implantation (TAVI) showed a significant benefit for patients with symptomatic severe aortic stenosis who had an extremely high surgical risk, a researcher reported here.

The 1-year rate of all-cause mortality or major stroke was 25.5% (95% CI 21.6%-29.4%), meeting the trial's primary endpoint by coming in under the goal of 43% (P<0.0001), according to , of Beth Israel Deaconess Medical Center in Boston.

The rate of major stroke was low at both 30 days (2.4%) and 1 year (4.1%), and paravalvular regurgitation improved over time, Popma reported at the Transcatheter Cardiovascular Therapeutics meeting here.

"I think the key thing for patients is that right now we only have one device here available in the United States and this data should hopefully form the basis for an approval of a second device that will allow us to treat patients with smaller vessels [and] bigger annulus sizes," commented , of Columbia University Medical Center, who moderated a press briefing at which the results were discussed. "So I think it would be a welcome addition to have as a whole."

Safety Results Deemed Encouraging

, of Henry Ford Hospital, said he was surprised by how safe the device was, pointing to the low rates of mortality and stroke and the improvement in paravalvular regurgitation.

"All of those things are good for patients and I'm actually very encouraged by the results of the trial," he told 乌鸦传媒視頻.

He noted that the FDA announced that it would not require an external expert panel before proceeding with its review of CoreValve for use in this subset of patients with an extremely high predicted risk from surgical aortic valve replacement.

Medtronic said that it anticipates approval for the device by the end of April, "which I think is great," O'Neill said, "because the more devices we have available, the wider the armamentarium to treat the patients."

Although multiple TAVI devices are available in Europe, only one such device has been approved for use in the U.S. -- the Edwards Sapien valve.

The was designed to support the approval of Medtronic's device. The trial included patients at high surgical risk -- in whom TAVI with CoreValve was compared with surgical aortic valve replacement -- and those at extreme surgical risk -- in whom TAVI with CoreValve was compared with historical data from patients treated with medical therapy.

In the extreme-risk group of patients, most were treated using iliofemoral access, and that is the group of patients for which Popma reported results. The analysis included 487 patients who had arteries that could accommodate an 18-French sheath.

The extreme surgical risk of the patients was determined by two clinical site cardiac surgeons and one interventional cardiologist based on assessments of comorbidities, frailty, and disability indicating a risk of operative death or serious, irreversible morbidity of 50% or greater at 30 days. The determination was confirmed by external review.

The average age of the patients was 83, the STS predicted risk of mortality was 10.3%, and the logistic EuroSCORE was 22.7%. Nearly all of the patients (92%) had New York Heart Association class III or IV symptoms at baseline.

Historical Data Used for Comparison

For the primary endpoint of all-cause mortality or stroke at 1 year, the patients treated with CoreValve were compared with historical data from patients treated with medical therapy because it was no longer considered ethical to randomize patients to standard therapy after the results of the PARTNER trial were presented in 2010.

The objective performance goal of 43% was estimated using a meta-analysis of five contemporary balloon valvuloplasty series and the control group of PARTNER Cohort B. The rate came in under that in the current trial, with low rates of both death and major stroke. In a continued access study of 873 patients enrolled after the trial ended, rates were even lower.

Those effects on clinical outcomes were accompanied by significant changes in symptoms. New York Heart Association class improved by at least one category in 90% of patients and by at least two categories in 60% of patients by 1 year.

And paravalvular regurgitation improved over time. At discharge, about half of the patients had mild or moderate regurgitation and the other half had no or trivial regurgitation. By 1 year, the rates were 32.9% and 67.1%, respectively.

Of the patients with moderate regurgitation at 1 month who survived to 1 year, 80% had a reduction in paravalvular regurgitation.

Several researchers questioned what could be behind the somewhat surprising finding, and Popma pointed to the method of sizing the valves used in the trial. All patients underwent coronary CT to have the valve size selected, and Popma said the investigators tended to be more aggressive in selecting a larger valve size.

Kirtane said more data are needed to see whether the reduction in regurgitation holds up.

Pacemaker Implantation Rates a Concern

Previous studies have shown that CoreValve is associated with higher rates of permanent pacemaker implantation compared with other TAVI devices, and in the current study 22.2% required a new pacemaker implantation at 30 days. That was on top of the 25% of patients who already had a pacemaker at baseline.

Kirtane said that the pacemaker rate was consistent with what was expected, and noted that despite the high rate of pacemaker implantation, there was still a significant improvement in all-cause mortality and major stroke in the trial.

O'Neill said that even though there is no proof that pacemaker implantation is associated with worse clinical outcomes, there is still some concern surrounding the issue.

"There is a huge problem in the hospital because the patients have to be maintained in the hospital for 3 or 4 days longer than they might have been just because there's a concern about late pacemaker implantation," he said, noting that costs would increase because of the longer length of stay and the expense of the pacemaker itself.

Overall, though, the results were received as positive.

, a cardiac surgeon and co-author of the PARTNER trial, noted that none of the centers that participated in the trial had prior transcatheter heart valve experience.

"Putting [the trial] in any light, the results are outstanding, but especially putting it in that light," he said at the press briefing.

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