Corevalve Registries Impress at One and Two Years as Randomized Trial Announced; Pacemaker Use Scrutinized

Shelley Wood

June 02, 2010

June 2, 2010 (Paris, France) — New registry data from operators using the CoreValve device for transcatheter aortic-valve implantations (TAVI) support the medium-term safety and efficacy of this fully percutaneous valve but have also refocused attention on the wide-ranging rates of pacemaker implantation by different centers using this device.

At last week's EuroPCR 2010 meeting, investigators from countries outside the US presented new outcome data for the self-expanding CoreValve, which is implanted transfemorally in the vast majority of cases (there is a small but growing number of patients treated with this device via a subclavian route.)

Registry results came on the heels of an announcement during the EuroPCR opening sessions of a large European, multicenter, randomized clinical trial comparing the CoreValve with surgical aortic replacement. The trial, to be called SURTAVI, is still in the planning phases but, pending regulatory blessings, is expected to start enrolling before the end of the year.

According to a press statement from CoreValve manufacturer Medtronic, the device, which is not approved--and, indeed, not even being studied--in the US, has been used in more than 10 000 patients in 32 countries and is the transfemoral valve of choice--used in three out of four transarterial valve-replacement procedures.

Two-Year Results Similar to Sapien

Dr Ulrich Gerckens (HELIOS Heart Center, Siegburg, Germany) presented two-year data on 126 patients treated at one of nine centers in Canada and Europe between 2006 and 2008. In this series, 62 patients had survived out to two years (11 patients had not reached two years; five subjects were lost to follow-up). Survival percentage at two years was just under 60%, down from 72% at the one-year mark. Two-year survival free from cardiac death or valve complications, however, was higher, at 73.6%.

The one-year numbers are comparable to figures presented at EuroPCR for the only other transcatheter aortic valve approved in Europe, the Sapien valve, as reported by heartwire last week.

According to Gerckens, improvements in functional and hemodynamic parameters were sustained over time; low levels of aortic-valve regurgitation postprocedure actually improved over time; and there was no evidence of structural valve deterioration, valve migration, or frame fractures by the two-year mark.

Elsewhere during the meeting, other investigators presented data from countrywide registries in Belgium, Italy, Germany, France, and the UK, typically including patients treated more recently, yielding one-year mortality rates ranging from 20% to 25%. In registries that included both the CoreValve and the Sapien, survival rates were similar for the two devices when implanted with the transfemoral approach.

Discussing the various national registry data, session moderator Dr Gerard Fournial (Hôpital Rangueil, Toulouse, France) concluded that the procedure success and longer-term clinical outcomes "justify the acceptance of TAVI in high-risk patients not suitable for conventional surgery." Moreover, he continued, as more and more data accumulate, it's clear that major adverse events stem from technical issues and inappropriate patient section. "These encouraging results may allow us to extend indications to less sick patients," he concluded cautiously.

What About Pacemaker Usage?

A panel discussion of the various registry findings, however, focused on use of pacemaker implantations. Earlier registry studies had already highlighted the much higher use of pacemakers in CoreValve-treated patients than Sapien-treated patients--25% vs 5% on average--but what emerged clearly in sessions at EuroPCR was the starkly different pacemaker usage between institutions and countries.

In the German registry data, for example, pacemaker implantation was 38% among almost 700 patients, the bulk of whom were treated with the CoreValve via a transfemoral route. By contrast, in Italy, new pacemaker usage with the CoreValve was 18.5% in a series of 757 successfully treated patients.

Dr Ralf Zahn (Herzzentrum Ludwigshafen, Germany), who presented the German data, acknowledged he was "disappointed" by the high use of pacemakers in Germany but explained that while the threshold of using a pacemaker was "very low in the beginning" operators are now "pulling back."

Likewise, Dr Sonia Petronio (University of Pisa, Italy), who presented the Italian data, noted that 18.5% was actually a median range but that usage varied widely among Italian centers, from 4% to 36%.

"There is still not a uniform way of deciding when to put in a pacemaker," she pointed out. In the Italian series, the major drivers of pacemaker usage were prior right bundle branch block (RBBB), with 48% of RBBB patients receiving a pacemaker, and lower placement of the device, with 38% of low-implantation patients receiving a pacemaker.

"There are still other factors that we need to recognize for each patient that would probably help us to know more exactly which patients would need a pacemaker," Petronio said. She also wagered a guess that most centers erred on the side of implanting a pacemaker in their early patients, out of fears that device implantation would lead to rhythm disturbances.

Speaking with heartwire , Dr A Pieter Kappetein (Erasmus Medical Center, Rotterdam, the Netherlands) singled out the "pacemaker issue" as one of the major unresolved questions for the CoreValve. While rates of pacemaker usage appear to be declining, he thinks reimbursement may be one part of the decision-making process, rather than patient needs. "If there is a restriction on [pacemaker] reimbursement, then your threshold for implanting one will be higher, while at some centers where it is reimbursed, people will say, 'Well, let's implant a pacemaker, just to be sure.' "

Other Unresolved Issues

Kappetein, as well as Dr Helene Eltchaninoff (University of Rouen, France), also stressed the need for long-term data on durability. As Eltchaninoff told heartwire , "The major unanswered questions are related to the durability of the valve, which is very important if you want to address lower-risk patients, because we know that surgical valves are working well for 15 to 20 years. Today, we only have two to three years of data on durability with transcatheter valves."

Indeed, the palpable interest in extending the indication for transcatheter valves to lower-risk patients was another topic for debate at EuroPCR, with mean EuroSCOREs among different registry results hinting that despite device labeling and practice guidelines that stipulate patients undergoing TAVI cannot be candidates for surgery, physicians are already treating lower-risk patients.

"People are starting to use these devices for other indications, thereby getting better results," Kappetein observed. "Everyone is saying 'Oh, [outcomes are improving because] there's a learning curve,' but I think that the results now are better than three years ago, not only because of the learning curve, but also because physicians are doing lower-risk patients."

Patients are also increasingly aware of TAVI procedures and demanding them, requests physicians should be denying to surgery-eligible patients, he noted.

And as Eltchaninoff reminded heartwire , while people "might hope" that results would be better in lower-risk patients, "we really don't know. . . . We have to be sure that the [adverse-event rate] will be also as low as possible--for vascular complications, for example--because we know that with surgery we have very good immediate results with a low mortality." Rather than implanting valves in younger, lower-risk patients who are candidates for surgery, Eltchaninoff believes the appropriate next step is to enroll lower-risk octogenarians, in whom surgery is typically ruled out on the basis of age, not comorbidities.

A Randomized Corevalve Trial

In fact, performing TAVI in lower-risk patients will be specifically addressed in the SURTAVI trial announced at EuroPCR, Kappetein said. He is one of the principal investigators, along with Dr Stephan Windecker (University Hospital, Bern, Switzerland), Dr Thomas Walther (University of Leipzig, Germany), and Dr Peter de Jaegere (Erasmus Medical Center), with Dr Patrick Serruys (Erasmus Medical Center) as the "godfather advisor" for the trial, Kappetein said. The trial is still in the planning phases but will likely enroll 1500 to 2000 patients, randomizing patients to TAVI or surgery, and will include patients with a EuroSCORE greater than 6. By contrast, mean logistic EuroSCOREs in the registry data presented at EuroPCR ranged from 20 to 28. "What we would like to include are patients who are 80 years old or more, but with lower comorbidities. While these patients may not achieve greater life expectancies with TAVI, they may benefit from shorter hospital stays and better quality of life, he said.

He and his coinvestigators hope to have the trial protocol finished by August or September and then will have it reviewed by the FDA in time for trial enrollment to start before the end of the year. Depending on the FDA's comments, it is possible that the trial would even be expanded to the US, he added.

While CoreValve and Sapien data dominated the EuroPCR TAVI sessions, that won't always be the case. Attendees at this year's meeting heard that there are now more than 20 new TAVI devices at various stages of preliminary testing.

Eltchaninoff disclosed being a proctor for and receiving research contracts from Edwards. Fournial disclosed being a speaker for Edwards. Gerckens disclosed being a proctor for Medtronic. Petronio disclosed being a consultant for Medtronic. Kappetein and Zahn disclosed having no conflicts of interest.


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