Real-World AV Replacement in France: All Eyes on Mortality as Volumes Go Up and Patient Risk Declines

The results show important trends, but operators should continue waiting for randomized data before offering TAVR to low-risk patients, experts caution.

Real-World AV Replacement in France: All Eyes on Mortality as Volumes Go Up and Patient Risk Declines

The overall volume of aortic valve replacements rose in France between 2007 and 2015, due in large part to the increased prevalence of TAVR, according to new registry data. And while both mortality and adverse events remained more common among TAVR-treated patients than those treated surgically in this series, rates of both declined over time in the two groups and notably were similar in the most elderly patients undergoing these procedures.

Despite these positive signs, operators should hold off before “pushing TAVR on all elderly patients and wait for the results of the randomized clinical trials in low-risk patients,” senior author David Messika-Zeitoun, MD, PhD (University of Ottawa Heart Institute, Canada), stressed to TCTMD.

“The low mortality observed in elderly patients similar to or lower than that of isolated aortic valve surgery is very encouraging, but should be tempered as slightly more stroke and pacemaker [implantation] were observed and only in-hospital outcome was available,” he added.

For the study, published in the April 17, 2018, issue of the Journal of the American College of Cardiology, Messika-Zeitoun along with lead author Virginia Nguyen, MD, PhD (Bichat Hospital, Paris, France), and colleagues looked at a total of 131,251 consecutive interventions—17% TAVR—from an administrative database between 2007 and 2015. Overall, aortic valve replacement as a whole increased over time (from 10,892 to 18,704; P for trend < 0.0001) mainly due to an increase in TAVR, overall (from 244 in 2009 to 6,722 in 2015; P for trend = 0.0004) and within all age categories. Surgical volume remained stable (from 10,892 in 2007 to 11,982 in 2015; P for trend = 0.18).

Comparing the data available on the two procedures, surgery was associated with a lower in-hospital mortality rate (3.9% vs 5.3%; P < 0.0001), a lower rate of pacemaker implantation (4.4% vs 14.0%; P < 0.0001), a lower rate of stroke (1.6% vs 2.4%; P < 0.0001), and a higher rate of acute renal failure (10.9% vs 6.9%; P < 0.0001) versus TAVR.

Of note, however, the average Charlson score remained higher for TAVR patients than for patients receiving surgery. In-hospital mortality rates associated with TAVR and surgery declined over time (P for trend < 0.01 for both), and the overall Charlson comorbidity index declined (P for trend < 0.05).

Caveats With Administrative Data

In an accompanying editorial, Martin Leon, MD, Tamim Nazif, MD, and Vinayak Bapat, MD (NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY), write that the study is strengthened by its size and “comprehensive nature of this inclusive administrative database, which allows for an analysis of procedure trends and real-world outcomes of all AVRs performed in France during the study period. However, the use of an unaudited, in-hospital, administrative database also presents significant limitations that must be considered in the interpretation of results, especially relating to comparative clinical strategy recommendations.”

Namely, they point out that the Charlson index is based on diagnostic coding and “has not been well validated as a surrogate for surgical risk assessment,” also noting that several known determinants of patient risk were not able to be captured by the database.

“Given these significant limitations, the current study and others like it are of interest and valuable from an epidemiological perspective, but they have limited utility to inform changes in clinical practice,” Leon, Nazif, and Bapat say.

Ted Feldman, MD (Evanston Hospital, Evanston, IL), who was not involved in the study, told TCTMD that this study “validates trends that we've seen in other similar national databases . . . and to see consistent reporting is always very helpful.”

What the editorialists get right is that they “are making sure that readers keep in mind the limitations of database studies,” Feldman said. The value of registry analyses like this, as well as those published from Germany and the US-based TVT Registry, “is their contributions to the totality of the data. They have tremendous value in that regard,” he added.

Feldman observed that because France has had a slower development of reimbursement for TAVR than Germany, suggesting “that could explain why the absolute TAVR volumes haven't overtaken surgery volumes” in France as has been seen in Germany. “But the trends are still pretty much the same,” he said.

Probably the most important trends to note from this database are the climbing risk scores and declining mortality in both surgical and TAVR patients, he said, echoing the authors’ comments in the paper that this could be attributed to a “combination of better patient selection, earlier intervention, and greater awareness of the benefits of valve replacement broadly among the whole practice community. [This] is a very positive and remarkable story.”

Still Waiting for Randomized Data

The editorialists caution that “the TAVR ‘tsunami,’ which is driving expansion of clinical indications to include low-risk surgical populations based on age alone, is threatening to out-distance the current level of evidence. A modicum of restraint is in order as we await the results of the ongoing randomized clinical trials of TAVR versus SAVR in low-risk patients. Once these data are properly analyzed, perhaps administrative database studies such as the current one may help to confirm the appropriate application of clinical trial results to real-world practice.”

Messika-Zeitoun agreed saying, “It's very promising [to see] results showing that we can now perform TAVR in elderly patients at very low risk. Going forward, it will be interesting to see if the mortality is still similar in the randomized [trials] as in our population-based study.”

Asked whether he thinks operators are becoming antsy to offer TAVR to low-risk patients, Feldman said that he doesn’t “believe that people are pulling the trigger early. I think that in the TAVR-practice community there is a healthy respect for some of the uncertainties in treating lower-risk patients.” The community is in support of waiting for the randomized low-risk trial results, which “will be here soon enough,” he concluded.

  • The study was partially funded by the RHU STOP AS.
  • Nguyen reports receiving support by a grant from the Société Française de Cardiologie and the Fédération Française de Cardiologie.
  • Messika-Zeitoun reports serving as a consultant for Edwards Lifesciences, Mardil, and Cardiawave and receiving research grants from Edwards Lifesciences and Abbott Vascular.
  • Leon reports receiving institutional research and educational grants from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott and serving as an unpaid member of the Edwards Lifesciences executive committee.
  • Nazif reports receiving institutional research and educational grants from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott and serving as a consultant for Edwards Lifesciences and Medtronic.
  • Bapat reports receiving institutional research and educational grants from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott and serving as a consultant for Edwards Lifesciences, Medtronic, and Abbott.
  • Feldman reports receiving institutional research support and consulting honoraria from Edwards Lifesciences and Boston Scientific.