TAVI Registry Updates ADVANCE the Field, Raise Hopes for Lower Stroke Rates

Shelley Wood

March 24, 2012

March 24, 2012 (Chicago, Illinois) — Low stroke rates in two registries tracking outcomes for the two leading transcatheter valves are raising hopes that the cerebrovascular events that concerned people in the pivotal PARTNER trial may not necessarily represent the real-world occurrence of this problem going forward. The new data may also help physicians inch toward a better understanding of who is best suited to receiving a transcatheter valve and who transcatheter aortic-valve implantation (TAVI) cannot help.

Dr Axel Linke (University of Leipzig Heart Center, Germany) presented six-month results from the large ADVANCE registry of the CoreValve (Medtronic) device, and Dr Josep Rodés-Cabau (Quebec Heart and Lung Institute, Quebec City) presented long-term outcomes among 339 patients treated with the Sapien valve (Edwards Lifesciences) in Canada. Both presentations were part of a featured interventional clinical studies session here at the American College of Cardiology 2012 Scientific Sessions.

An ADVANCE for the Field

In ADVANCE, 1015 patients were enrolled in 12 countries between March 2010 and July 2011 from 44 centers--all of which had at least 40 prior procedures under their belts prior to enrolling patients in the registry. Patients had an average age of 81, and mean logistic EuroSCORE was 19.2, although Linke stressed that he believed this score did not accurately capture the frailty of many of the patients enrolled.

At 30 days, major adverse cardiac and cerebrovascular events (MACCE) had occurred in 8.3% of patients. Rates of total mortality and cardiac mortality were 4.5% and 3.4%, respectively. Strikingly, major strokes occurred in just 2.9% of patients, while major bleeding occurred in 9.7% and life-threatening or disabling bleeding occurred in 4% of patients.

At six months, all-cause mortality was 12.8% and cardiovascular mortality was 8.4%. When mortality rates were further analyzed, not surprisingly, mortality was higher among patients with EuroSCOREs greater than 20, at 17.3%.

In the Q&A following Linke's presentation, Dr Neil Moat (Royal Brompton and Harefield NHS Foundation Trust, UK) pointed to the low stroke rate at 30 days--a rate at odds with PARTNER cohort A, where the rate of major stroke in surgical high-risk patients who underwent TAVI was 3.8% at 30 days (and all stroke and transient ischemic attack [TIA] was 5.5%). Likewise, the major stroke rate in PARTNER cohort B (among TAVI-treated patients not suitable for surgery) was 5%.

"We were extremely pleased with the low stroke rates," Linke acknowledged. "So far we don't have an explanation." One might be that the ADVANCE registry included operators/centers that were already experienced with the device. Another reason, he said, might be the different way in which the CoreValve is deployed, as compared with Sapien. The Sapien is "aggressively" oversized, potentially crushing calcifications within the valve, leading to embolization in the bloodstream. By contrast, the self-expanding CoreValve "may be a more passive process," Linke said.

Asked about these device-expansion differences as a possible explanation for the lower stroke rate in ADVANCE, Dr David Holmes (Mayo Clinic, Rochester, MN), who was not a part of either registry, called the theory "a possibility" but stressed there are too many unknowns to compare the two TAVI devices. "I think these are very different devices, and the next generation of devices--which are already here--are very different again. So there will be device questions, number one; there will be patient questions, number two; and there will be adjunctive-therapy questions, number three--all of which may be independent predictors of outcomes."

Also of note, in ADVANCE, was a pacemaker implantation rate of 26%--in keeping with other published series of the CoreValve in Europe, where the device is approved, Linke said. Bleeding also proved to be a talking point, with Dr Antonio Colombo (Columbus Hospital, Milan, Italy) raising concerns about the 9.7% rate of major bleeding, including a 4% rate of life-threatening bleeding.

"I believe the dose of heparin we are using in these patients is probably inappropriate," Colombo said.

Canadian Experience With the Sapien

In the second registry presentation, Rodés-Cabau presented data out to four years (median three years) among 396 patients treated between January 2005 and June 2009 at six centers in Canada. At four years, half of the patients had died, with nearly identical survival rates among patients treated with a transapical approach and patients treated with a transfemoral approach.

The outcome data--with expanded patient numbers--largely reflect those of a paper published by Rodés-Cabau and colleagues in 2010 from the same series.

Among the causes of noncardiac deaths at four years, stroke made up 8.1% of cases, far less than the major causes, which were pulmonary or renal in nature. And for the entire series, Rodés-Cabau noted, the 30-day stroke rate in this series (which included the very first cases performed in Canada) was 2.3%. Of note, the need for a pacemaker was just 4.9% at 30 days in the series presented by Rodés-Cabau.

Asked about the low stroke rate in his series, Rodés-Cabau acknowledged that there have been "a lot of questions about thrombogenicity of these valves, and I think these results don't support this hypothesis. . . . The [Canadian] data for stroke correlates with other registries, and PARTNER had relatively different results with regard to these registries worldwide."

Predicting Who Will Benefit From TAVI

In his presentation, Rodés-Cabau focused on what he and his colleagues had identified as the major predictive factors of late mortality in TAVI recipients in their series, namely chronic obstructive pulmonary disease and chronic kidney disease, followed by chronic atrial fibrillation and frailty. Noncardiac deaths were responsible for two-thirds of the deaths in the Canadian series, he stressed.

Even so, he says, the relatively small number of patients "doesn't allow us to give firm recommendations about patient selection. I look at this as a first step in understanding TAVI risk stratification." The focus in the early patients was on technique; more recently it has shifted to optimizing patient selection. "What we've seen is that a significant number of these patients die within the first months or years of the procedure, and we have identified four important comorbidities that are very prevalent" and that should be taken into account when making treatment decisions.

At his hospital, he says, a pulmonologist or nephrologist will be brought into any discussion of a TAVI decision in a patient with relevant comorbidities. "In our daily experience we have been refusing many more patients now than we were in the past."

To heartwire , Holmes put it even more succinctly, saying that physicians will have to come to terms with a simple truth: "There will be some patients who we want to treat who are dying from aortic stenosis and there will be some patients who are dying with aortic stenosis--and those, we cannot treat and we cannot help."

Importantly, Rodés-Cabau observed, valve function remained stable up to four years in patients who underwent follow-up echo; only mild nonsignificant changes in transvalvular gradient and valve area were seen, and no changes were seen in presence or degree of residual aortic regurgitation.

Linke disclosed being a proctor for Medtronic CoreValve and receiving travel expenses from the company. Rodés-Cabau disclosed serving as a consultant for Edwards Lifesciences and St Jude Medical.

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