TAVI with Sapien 3 may be better than surgery for intermediate-risk patients



Vinod Thourani
Vinod Thourani

ccording to Vinod H Thourani (Emory University School of Medicine, Atlanta, USA) and others, intermediate-risk patients undergoing transcatheter aortic valve implantation (TAVI) with the Sapien 3 device (Edwards Lifesciences) have a lower rate of a primary composite endpoint of all-cause death, all strokes, or moderate/severe aortic regurgitation than intermediate-risk patients undergoing surgical aortic valve replacement. They claim that this finding suggests that TAVI with the Sapien 3 device “may be the preferred treatment alternative” for intermediate-risk patients.

Writing in The Lancet, Thourani et al note that encouraging clinical outcomes with earlier-generation TAVI systems in inoperable and high-risk patients—“as well as rapid device refinements that led to improved clinical outcomes”—has generated interest in using TAVI for lower risk patients. They add that an observational study of the next-generation Sapien 3 TAVI system indicated that the device was associated with good 30-day outcomes in both high and intermediate-risk patients. Therefore, for this study, the authors aimed “to report one-year outcomes with Sapien 3 in intermediate-risk from this observational study and then use a pre-specified propensity score analysis to compare these outcomes with those for similar patients given surgical aortic valve replacement in the PARTNER 2A randomised trial.”

They explain that in PARTNER (Placement of aortic transcatheter valves) 2A, intermediate-risk patients with severe aortic stenosis were randomised to undergo TAVI with the earlier-generation Sapien XT (Edwards Lifesciences) valve or undergo surgery. According to Thourani et al, “intermediate-risk” was defined as patients with a Society of Thoracic Surgeons (STS) score of 4–8% or those with a STS score of <4% who the heart team had deemed to be at intermediate risk because “they had risk factors not presented within the predictive score (eg. liver disease, frailty, and pulmonary hypertension)”. The primary endpoint was a composite of all-cause death, all strokes, and the incidence of moderate or severe aortic regurgitation.
One-year data were available for 963 patients from the Sapien 3 observational study and for 747 surgical patients in the PARTNER 2A study. Thourani et al report: “In each of the quintiles [of propensity-matched groups], patients undergoing TAVI had a lower incidence of the composite primary endpoint than did the group who received surgery—ranging from -14.1% in quintile one to 4.3% in quintile five. The non-inferiority analysis was based on the pooled weighted proportion difference of -9.2% favouring TAVI, which was below the 7.5% non-inferiority margin.” They then performed a superiority analysis that revealed that TAVI was also found to be superior to surgery in terms of the composite endpoint (-9.2% difference; p<0.0001) and for the individual outcomes of death (-5.2% difference; p=0.0003) and stroke (-3.5% difference; p=0.0038). However, surgery was associated with a lower rate of moderate or severe aortic regurgitation. At one year, they noted a 1.5% rate of moderate or more than moderate aortic regurgitation in the TAVI arm. Furthermore, among the Sapien 3 cohort, patients with a moderate or severe aortic regurgitation had a significantly increased risk of all-cause mortality at one year.

The authors note that the one-year outcomes (and the 30-day outcomes) are better than those reported in previous studies of TAVI in intermediate-, high-, extreme-risk patients. “The reasons for improved outcomes are probably multifactorial and include strategic case selection and planning, increased operator experience, facilitated in-hospital patient care pathways, and device enhancements,” they explain. Thourani et al also state that “importantly” the improved profile of the Sapien 3 valve compared with earlier generation Sapien valves has “encouraged the expanded use of percutaneous transfemoral procedures (as for 88% of patients in this study), which have been associated with favourable short-term and long-term outcomes compared with transapical procedures.”

Furthermore, while acknowledging that the one-year rate of moderate or severe paravalvular with Sapien 3 was higher than that with surgery, the authors note that the absolute frequency of paravalvular regurgitation “was lower than has been previously reported in TAVI studies” and unlike the previous studies, only moderate or severe paravalvular leak—and not mild—was associated with increased late mortality. Thourani et al comment: “The Sapien 3 valve combined with multidetector computed tomography (MDCT) valve sizing and more precise valve positioning techniques might be responsible for the reduction of moderate or severe paravalvular regurgitation to sufficiently low levels that treatment of lower-risk patients should no longer be discouraged.” However, they add that long-term follow-up of patients with mild paravalvular leak is necessary to confirm that it does not negatively affect outcomes.

Thourani et al conclude: “The comparison of the one-year results with those from the surgery cohort from PARTNER 2A demonstrates that Sapien 3 was superior to surgery for these important clinical endpoints [ie. death and stoke] and suggests it to be the preferred treatment alternative in these patients. Additional studies (including randomised controlled trials) are necessary to corroborate these findings and before extending the use of TAVI to low-risk patients.”

This propensity-score analysis adds to the growing evidence base for the use of TAVI in intermediate-risk patients. The day before the analysis was published in The Lancet, the results of the PARTNER 2A analysis were published in The New England Journal of Medicine—both studies were published to coincide with their respective presentations at the 2016 American College of Cardiology (ACC) meeting (2–4 April, Chicago, USA).

In PARTNER 2A, intermediate-risk patients were randomised to receive TAVI with the Sapien XT device (1,011) or surgical aortic valve replacement (1,021). Speaking at the ACC, investigator Craig R Smith (Columbia University Medical Center, New York, USA) reported that the patients who underwent TAVI had a similar incidence of the primary endpoint (all-cause mortality or disability stroke) at two years as those who underwent surgery—meeting the study’s hypothesis that TAVI with Sapien XT would be non-inferior to surgery in this cohort of patients. However, he added that in both the intention-to-treat analysis and the as-treated analysis, the primary endpoint was significantly reduced in patients who underwent transfemoral TAVI compared with those who underwent surgery. Smith also reported that TAVI was associated with reduced acute kidney injury, severe bleeding, new atrial fibrillation, and length of stray while surgery was associated with reduced vascular complications and paravalvular regurgitation. He concluded: “Long-term durability assessment of transcatheter bioprosthetic valves are still lacking and extrapolation of these findings to low-risk patients require clinical trial validation.”

Smith told Cardiovascular News: “We have enough durability data now to begin experimenting with TAVI in low-risk patients in the context of carefully controlled clinical trials, and the FDA obviously agrees with this assessment. However, we must acknowledge that our optimism will appear misplaced if a premature valve-failure signal emerges in a few years.”

Also at the ACC, Medtronic announced that subgroup data from the CoreValve US Pivotal trial indicate that TAVI with CoreValve is associated with significantly better outcomes at two years than surgery among patients with a STS score of ≤7% (all-cause mortality was 15% with CoreValve vs. 26.3% with surgery; p=0.01). Study investigator Michael Reardon (Houston Methodist DeBakey Heart & Vascular Center, Houston, USA) comments: “It was encouraging to see that CoreValve patients with lower STS mortality risk scores within the High Risk Study achieved a superior survival benefit relative to surgery as did all patients at two years.”