NOTION: 5-Year Outcomes for TAVR Match SAVR in Low-Risk Patients

ORLANDO, FL—At 5 years, there are no differences in all-cause death, stroke, myocardial infarction, or all of these combined between low-risk, elderly patients treated with transcatheter or surgical aortic valve replacement in the NOTION trial.

As in updates from previous years, TAVR-treated patients had more moderate prosthetic regurgitation than was seen in the SAVR group, said H. Gustav Horsted Thyregod, MD, PhD (Copenhagen University Hospital, Denmark), who presented the results here at the American College of Cardiology 2018 Scientific Session.

Moreover, pacemaker implantation, which was significantly more common in TAVR patients, was associated with increased mortality down the road.

NOTION enrolled an all-comers population, with the criteria that they be 70 years or older with severe aortic stenosis and a life expectancy of 1 year or greater. Among the 280 enrolled and randomized patients, STS scores were a mean of 3 in both groups, with more than 80% having STS scores less than 4.

At 5 years, the primary endpoint of all-cause mortality, stroke, or MI was 39.2% among TAVR-treated patients and 35.8% in SAVR-treated patients, a nonsignificant difference. In any analysis that looked only at subjects with STS scores of less than 4%, again there were no significant differences between groups.

All-cause mortality was identical between groups at 27.7%—the lowest recorded rate for a TAVR trial at 5 years, Thyregod noted. Stroke was numerically higher among TAVR-versus SAVR-treated patients (10.5% and 8.2%, respectively), while MI rates were nearly identical at 8.6% and 8.7%.

Where differences emerged was in rates of aortic valve regurgitation, which has been consistently and statistically more common in NOTION among TAVR-treated patients at every year postprocedure. It remained marked at 5 years.

Aortic Regurgitation at 5 Years

While investigators could not document a difference in TAVR/SAVR outcomes relative to aortic regurgitation severity, but they did see an important signal for pacemaker implantation. At 5 years, 41.8% of TAVR patients had been implanted with a pacemaker, up from 34% at 30 days. In the SAVR group, the 5-year pacemaker rate was just 8.4%. That difference looked to track with mortality: among those who received a pacemaker, mortality was 38.2% compared with just 21.7% in the no-pacemaker group, a trend that narrowly missed statistical significance (P = 0.07).

“Determining the longevity of TAVR prostheses will require longer-term follow-up,” Thyregod said. “The NOTION trial has the capacity to study this, since we have many patients who are alive.”

More Answers Coming

During the Q&A following NOTION’s presentation, Thyregod was asked whether NOTION, with just 280 randomized patients, was adequately powered to show a difference.

In response, he agreed that the original power calculations may have been overly optimistic. The trial got underway, he reminded the audience, back in 2009. “One could say this is more of a pilot study for those [larger, randomized] studies going on right now, and obviously it’s great that we can follow [the NOTION] patients for a longer time.

A principal investigator on one of these larger trials now ongoing is Martin Leon, MD (NewYork-Presbyterian/Columbia University Medical Center, New York, NY), who congratulated the NOTION researchers for achieving 100% follow-up at 5 years in a low-risk study launched so soon after the devices debuted. 

As to the high survival rates in both groups, Leon said: “These are lower risk patients, so you would expect lower mortality. [Still,] to have a 28% 5-year mortality that’s the same as surgery is encouraging.”

Leon’s principal concerns were with the high rates of pacemaker use and paravalvular leak (PVL) in the TAVR-treated patients. “Especially when you are dealing with lower-risk patients, the idea of having more than a 40% pacemaker rate is certainly distracting,” he said. “I would also argue, the PVL rate, although not associated with mortality in this study, is clearly higher and certainly in larger populations of lower-risk patients you would argue that this is not a good thing. . . . Trying to wear my surgeon’s hat, I’d say the jury is still out as to what we’d want for our low-risk patients.”

Leon also pointed to a numerical difference in endocarditis rates between the two groups: 11.3% for TAVR and 5.8% for SAVR, something he found “intriguing.”

According to Thyregod, NOTION investigators are digging into the endocarditis numbers and will present those at the upcoming EuroPCR meeting.

Speaking with TCTMD following the session, senior investigator for NOTION, Lars Sondergaard, MD (The Heart Center, Rigshospitalet, Copenhagen, Denmark), said he’s not particularly concerned with the high pacemaker rates or the paravalvular leaks.

“This was a very early trial. It started 2 years after CoreValve was approved in Europe, without any resheathable system, and also at that time we really didn’t know which patients needed a pacemaker and which didn’t, so we put more pacemakers in then than we would for the same conduction abnormalities today,” Sondergaard commented.

Yet despite the high pacemaker rates and PVL rates, the TAVR and SAVR patients have the same outcomes, he pointed out. “You can just imagine how that might be today, with lower pacemaker [implantation] rates, lower paravalvular leaks, and better procedural outcomes. Ten years down the line, it’s going to be very interesting to see the current low-risk studies come out.”

Of note, NOTION 2 is also in the works: a low-risk, randomized trial that has set patient age at a maximum of 75. With that requirement, Sondergaard said, they are really hoping to get answers not only in low-risk patients, but in younger patients as well—ideally in their late 60s, he told TCTMD. Mean age in NOTION was 79.