Transcatheter Aortic-Valve Replacement with a Self-Expanding Prosthesis (U.S. CoreValve High Risk Study)
Selected in The New England Journal of Medicine by G. Harris
David H. Adams, Jeffrey J. Popma, Michael J. Reardon, Steven J. Yakubov, Joseph S. Coselli, G. Michael Deeb, Thomas G. Gleason, Maurice Buchbinder, James Hermiller, Neal S. Kleiman, Stan Chetcuti, John Heiser, William Merhi, George Zorn, Peter Tadros, Newell Robinson, George Petrossian, G. Chad Hughes, J. Kevin Harrison, John Conte, Brijeshwar Maini, Mubashir Mumtaz, Sharla Chenoweth, and Jae K. Oh for the U.S. CoreValve Clinical
N Engl J Med 2014; 370:1790-1798
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Surgical aortic valve replacement (AVR) has for many years been the only treatment option shown to prolong life in patients with severe aortic stenosis. Unfortunately surgical AVR is not always an option in these patients. The reasons may include severe co-morbidities (making surgery a probable death sentence), porcelain aorta and previous mediastinal radiation.
The benefits (incl. non inferiority) of percutaneous aortic valve implantation, using the balloon expandable EDWARDS valve vs. medical therapy and surgery were demonstrated in the PARTNER trial.
This trial (US CoreValve Trial), not only evaluated a different type of percutaneous aortic valve (self expandable), but also evaluated for possible superiority vs. surgery.
The benefit of the CoreValve vs medical therapy was demonstrated in a study published in the Journal of the American College of Cardiology 2014, March 19 (online). The all cause mortality at 12 months was 8.4% in the TAVR group vs. 43% in the medical treatment group.
The 1e endpoint in this trial was all cause mortality at 1 year.
Secondary endpoints included the composite of major adverse cardiovascular and cerebrovascular events (defined as a composite of death from any cause, myocardial infarction, any stroke or reintervention) at 30 days and 1 year, as well the individual components of this composite.
Echocardiographic indices examined, included the change in the mean aortic-valve gradient and the change in the effective orifice area from the baseline to 1 year.
- All cause mortality at 1 year was significantly lower in the TAVR group compared to the surgical group (14.25 vs. 19.11%).
- In this patient population, TAVR was demonstrated to have an absolute risk reduction of 4.9% when compared to surgical AVR (P<0.001 for inferiority & P= 0.04 for superiority).
- The results were similar in the intention to treat analysis; the event rate was 13.9% for TAVR and 18.7% for surgical valve replacement.
- There was no significant difference in the stroke rate between the two groups.
- TAVR was shown to be non-inferior in terms of echocardiographic indexes of valve stenosis, functional status and quality of life.
- The rates of moderate or severe paravalvular regurgitation were higher in the TAVR group, however most of these patients (76.2%) had mild or no regurgitation at 1 year.
- Surgery had a significantly higher incidence of new onset or worsening AF, acute kidney injury and major bleeding.
This study is not a comparative to the Partner trial as the groups and Euro-scores are not matched.
According to the authors, the improved aortic regurgitation at 1 year was ascribed to “the use of CT assessment of aortic annular diameter for valve-size selection before enrollment, higher placement of the valve within the aortic annulus and sustained expansion of the nitinol frame”. The net effect of AR in this trial is very exciting.
The increased use of permanent pacemakers 19.8% vs 7.1% (P<0.001) in the TAVR group is a point to take note of. This is higher than the 11% in the 2011 Swedish registry. A reason given for this lower incidence in the Swedish registry was the higher placement of the valve as well as the avoidance of predilation. I am not aware to what extent this thinking was used in the USCoreValve trial.
In the Pragmatic Plus Initiative (JACC vol. 61. Nr 8, 2013) there was a much greater need for permanent pacing in CoreValve group compared to the Edwards Sapien valve (22.5% vs. 5.9% ; P <0.001).
I think this trial clearly demonstrates the benefit of TAVR in these high risk patients. I do think this trial is not a license to perform TAVR in any patient with severe aortic stenosis, needing a new aortic valve. We still need long- term data. However there should be no reason why patients who are at high surgical risk, but still surgical candidates, who are not expected to outlive the lifespan of a bioprosthetic valve, should not be offered this option. Even if they were to need a new valve, then valve in the previous TAVR valve would probably be feasible in most.
This trial offers a reasonable alternative for TAVI. New valves in development and testing (Boston Lotus, Saint Jude Portico, Direct Flow, Jena Valve, Next generation Medtronic valve, Edwards 3rd generation valve etc.) and technologies including profile reduction from 18 French to 16 French as well as anti-calcification technology are expected to expand those alternatives in future.