For patients with severe aortic stenosis who cannot withstand surgery, transcatheter aortic valve implantation markedly reduces mortality from any cause, cardiovascular mortality, the need for hospitalization, and cardiac symptoms, according to a report from the PARTNER trial published online Sept. 22 in the New England Journal of Medicine.
Dr. Martin B. Leon
In what they described as the first multicenter randomized trial comparing transcatheter aortic valve implantation (TAVI) with standard therapy in such patients, researchers found that 1-year all-cause mortality was 20 percentage points lower with TAVI. On that basis, transfemoral “balloon-expandable TAVI should be the new standard of care for patients with [severe] aortic stenosis who are not suitable candidates for surgery,” said Dr. Martin B. Leon of Columbia University Medical Center/New York Presbyterian Hospital and his associates in the industry-funded Placement of Aortic Transcatheter Valves (PARTNER) study.
Previous studies of TAVI, which has been adopted rapidly worldwide for the treatment of severe aortic stenosis since its inception in 2002, have all been “observational registry studies, without standardization of end-point definitions (and unpublished data) and without control populations.” The PARTNER study was designed to collect rigorous, evidence-based clinical data to substantiate the procedure’s benefits, compared with current standard treatment, the investigators said.
The 358 study subjects were enrolled at 21 sites throughout the United States and in London and Vancouver in 2007-2009. Half were randomly assigned to undergo TAVI and half to receive standard therapy, and all were followed for 1-3 years.
The primary end point – death from any cause at 1 year follow-up – was 31% with TAVI and 51% with standard treatment. Cardiovascular mortality also was markedly lower with TAVI (21%) than with standard treatment (45%).The composite end point of death from any cause or repeat hospitalization within 1 year also was dramatically lower with TAVI (43%) than with standard treatment (72%).
Symptoms also were significantly reduced in the TAVI group. At 1 year, 75% of surviving patients who had undergone TAVI were asymptomatic or had only mild symptoms, compared with 42% of those who had received standard therapy, Dr. Leon and his colleagues said (N. Engl. J. Med. 2010 Sept. 22 [10.1056/NEJMoa1008232]).
Major neurologic events, vascular complications, and bleeding events were more common in the TAVI group. In particular, major stroke was more common with TAVI at 30 days (5%) and 1 year (8%) than with standard therapy (1% and 4%, respectively), but these differences did not reach statistical significance.
On echocardiography, the mean aortic-valve area increased and the mean aortic-valve gradient decreased with TAVI, both significant results that were maintained through 1-year follow-up. The incidence of moderate or severe transvalvular aortic regurgitation was 1% at 30 days and 4% at 1 year in the TAVI group, compared with 17% and 15%, respectively, with standard treatment.
“Undoubtedly, the large femoral access sheaths that are required to insert [current] TAVI system[s] contributed to the frequent occurrence of vascular complications and bleeding events. Ongoing studies are assessing the use of a lower-profile valve and support frame, which may reduce vascular complications, allow patients who have smaller iliofemoral arteries than did patients in this study to undergo this procedure, and facilitate percutaneous access and closure,” the investigators added.
The PARTNER study was sponsored by Edwards Lifesciences. Dr. Leon and his associates reported numerous ties to drug and device manufacturers including Edwards, Medtronic, Sadra Medical, Heart Leaflet Technologies, St. Jude Medical, Abbott, Lilly, Johnson and Johnson, Daiichi Sankyo, Sorin Medical, Entourage Medical Technologies, CoreValve, and Direct Flow Medical.