By Mark McCarty, Regulatory Editor
The TAVR wars heated significantly at the annual meeting of the American College of Cardiology, where a new set of data for the Corevalve series of devices demonstrated that the Dublin-based Medtronic plc offering beats surgical aortic valve replacement on several scores for intermediate-risk patients, a population already served by a TAVR offering from Edwards Lifesciences Corp. of Irvine, Calif.
The 17th annual scientific sessions held by the American College of Cardiology commenced with the usual late-breaking clinical trial data releases, with the data from Surtavi serving as the premier device study presented on day one. Michael Reardon, a principal investigator in the 1,764-enrollee study, reminded that the study was conducted across more than seven dozen sites in the U.S., Canada and Europe. Numerically speaking, the Medtronic units outperformed surgical aortic valve replacement (SAVR) handily in terms of the primary endpoint of all-cause death and stroke (12.6 percent for TAVR and 14 percent for SAVR) at two years, but this measure failed to hit the benchmark for demonstrating superiority for the study article, although the Corevalve units’ performance sufficed to hit the non-inferiority standard.
Despite the sheer volume of enrollment, Surtavi was a Bayesian trial that was principally populated by the legacy Corevalve in the device arm, while the successor, the Evolut R, accounted for 16 percent of the total TAVR devices used in the study. Operators handling the SAVR cases were allowed their pick of available surgical valve offerings in an effort to mirror real-world outcomes, which Surtavi replicated at least in one characteristic: Nearly one in four on the study article needed a pacemaker in this study, similar to a figure seen in a previous study of Medtronic valves in high-risk patients. (See Medical Device Daily, March 18, 2015.)
The enrollees, who on average were nearly 80 years of age in both the roughly numerically equal arms, were all in the range of 4.4 to 4.5 on the risk scoring system devised by the Society of Thoracic Surgeons. The TAVR arm included some patients who underwent percutaneous intervention for the coronary arteries while some of the SAVR patients also underwent bypass surgery, and one of the inclusion criteria was that the patient be in at least stage II heart failure.
Reardon, who had presented two-year Corevalve data for high-risk patients at ACC 2015, said the original enrollment had been winnowed to 1,660 by the time it came to attempt device placement. He said the 24-month data for all-cause mortality and disabling stroke presented “a very robust statistic for non-inferiority.” The all-cause death at 30 days favored SAVR, which was 1.7 percent while TAVR’s 30-day mortality was 2.2 percent. Of the SAVR figure, Reardon said “this is extraordinarily good surgery.” The numbers flipped by two years, however, with TAVR all-cause mortality at 11.4 percent while SAVR yielded 11.6 percent. “TAVR stood toe-to-toe with surgery” and won on all-cause death at two years, Reardon emphasized.
Reardon remarked that this is the third consecutive study showing TAVR imposes a lower rate of stroke than SAVR, but he said the data do little to answer the question of whether hemodynamic performance is particularly important. Reardon said he was “very taken aback,” by the persistence of the pacing problem, which he said will greatly affect patients who have a considerable life expectancy in front of them. “I think this is an engineering … and site placement thing,” Reardon continued, although he added that the ability to retrieve and re-place the Medtronic units gives the operator more breathing room to ensure proper device placement.
Among the other encouraging signs to come out of Surtavi is that the Medtronic devices imposed a stroke rate of 2.6 percent at two years, only slightly more than half the stroke rate of 4.5 percent of the SAVR arm. One of the confounders on the point of pacemaker in Surtavi was that the rates between Corevalve and the Evolut R iteration were very similar (25.5 percent for the legacy device and 26.7 percent for the newer edition), although the fact that the Evolut R made up only about one in six of the TAVR devices in this study complicates efforts to draw any conclusions on that point.
Reardon told Medical Device Daily that it can be difficult for less experienced operators to avoid placing a TAVR device without interfering with the function of the atrioventricular node, a predicament incurred when the device is positioned in such a manner as to impinge upon the outflow tract. Overcompensating for this hazard with the original Corevalve could lead to some problems with obtaining a proper fit of the device into the aortic annulus, he said.
Reardon said the clinical discussion for device selection revolves around several factors.
“We look at things such as whether there’s a lot of calcium in the outflow tract,” he said, noting that a self-expanding device is perhaps a better bet to avoid rupturing the annulus, which could prove lethal. On the other hand, he said, a practitioner might go to a balloon-expandable unit if the width of the aortic sinus exceeds a certain benchmark, although most of the variability in sinus width is indifferent to device type. Reardon said the ability to reposition the Medtronic offering is really the best argument for the Evolut R.
When asked about private payers, Reardon said, “most of them have been willing to cover [TAVR] in the high-risk group,” although they are obviously less inclined at present to cover these devices for intermediate-risk patients. “The bigger problem is not the payer,” Reardon said, explaining that a hospital’s chief financial officer will say that SAVR “has one of the highest contribution margins in the hospital, and you want to replace it with a TAVR, which barely has a contribution margin.” As for the patients, “they all want TAVR,” Reardon shrugged.
The Evolut Pro is scheduled to debut at ACC 2017 on March 18, and Reardon said the device “has an external skirt to cut down on paravalvular leak. Stay tuned, it’s going to move things forward,” he advised.
TAVR WARS HEATING UP AGAIN
The competitive temperature was on display on March 17, as demonstrated by the full-page ad taken out by Edwards for its Sapien 3 TAVR device in the ACC.17 Daily, the circular published by the college each day during the ACC’s annual scientific sessions. The Edwards advertisement bragged that the company currently has the only TAVR offerings approved by the FDA for use in intermediate-risk patients, although the numbers from Surtavi suggest Edwards will lay sole claim to that population for only a little while longer.
Larry Biegelsen of Wells Fargo of San Francisco said in an investor’s note that the data from Surtavi should prod the FDA to expand the device’s indications to intermediate-risk patients. Biegelsen pointed out that SAVR performed substantially better on the primary endpoint in this study than was anticipated, mostly because of a lower mortality rate than has been seen in other studies, such as Partner 2A, a study of the Edwards Sapien XT and Sapien 3.
Biegelsen noted that Edwards may argue that the data for the Sapien 3 device as seen in Partner 2A bested the Surtavi data for Corevalve units in terms of moderate to severe paravalvular leak and rate of pacemaker implant, but that Medtronic can resort to the assertion that those Sapien 3 data were drawn from an observational study that employed propensity matching to filter out bias. The problem for Medtronic with the Evolut R iteration is that the pacemaker rate was roughly double that of the Sapien 3 (nearly 26 percent versus 12.4 percent on the Sapien 3), and the rate of paravalvular leak was nearly triple for the Medtronic items against the Sapien 3. Still, Biegelsen observed, Medtronic has the Evolut Pro waiting in the wings, a device Medtronic is expected to bring to market later this year.
An investor note from Rick Wise at Stifel Financial Corp. of St. Louis, characterized Reardon’s presentation as positive for both Medtronic and Edwards because the data “argue for continued, steady TAVR adoption” for intermediate-risk patients in the coming years. Wise commented that the Surtavi data might have been more persuasive had the entirety of the device arm had been populated by the Evolut R.
“Any lingering hesitancy about referring potential patients [for TAVR] should gradually diminish,” Wise said, noting that the comparative stroke rate at 24 months was 2.6 percent for the TAVR units and 4.5 percent for the surgical arm. He said Medtronic has already forwarded the Surtavi data on to the FDA, stating that the approval process “would likely take three to six months.” He rated Medtronic’s shares a hold with a target price of $84.