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Two Studies of a Self-Expanding Bioprosthesis for Severe Aortic Stenosis

Summary and Comment |
March 29, 2014

Two Studies of a Self-Expanding Bioprosthesis for Severe Aortic Stenosis

  1. Howard C. Herrmann, MD

The new kid on the TAVR block beats surgery.

  1. Howard C. Herrmann, MD

By offering an alternative to surgery, transcatheter aortic valve replacement (TAVR) has changed the treatment landscape for patients with severe, symptomatic aortic stenosis (AS). In the U.S., a balloon-expandable system (Sapien) is approved for AS patients who are at extreme risk (inoperable) or high risk (Society of Thoracic Surgeons [STS] 30-day mortality risk >≈8%). The FDA recently approved a self-expanding TAVR platform (CoreValve) for extreme-risk patients on the basis of data from a prospective nonrandomized study. Results of that study and from a separate randomized comparison of TAVR with surgery in high-risk patients have now been published. CoreValve's manufacturer funded both studies.

The nonrandomized study, conducted at 41 centers, involved 489 patients (mean age, 83; 52% women; >90% with class III or IV symptoms, STS risk >≈10%, and frequent frailty or disability) whom two cardiac surgeons and one interventional cardiologist estimated would have a >50% risk for mortality or irreversible morbidity within 30 days after surgery. Incidence of the primary endpoint — all-cause mortality or major stroke at 12 months — was 27% with CoreValve, significantly lower than the 43% objective performance goal derived from a weighted meta-analysis of 7 balloon valvuloplasty studies and the PARTNER B trial). The study patients' all-cause mortality rate was 8.4% at 30 days and 24.3% at 1 year; stroke rates were 2.3% at 30 days and 4.3% at 1 year. Other important endpoints included a new permanent pacemaker in 21.6% of patients at 30 days, mean improvement of 1.6 NYHA classes, and a 9.7% rate of moderate paravalvular regurgitation at discharge that decreased to 4.2% at 1 year.

In the multicenter, randomized trial, 795 patients (mean age, 83; 47% women; STS 30-day risk, 7.4%) deemed by the institution to be high risk because their estimated postsurgery 30-day mortality risk was >15% either received CoreValve or underwent surgery. In an as-treated analysis (747 patients), incidence of the primary endpoint of 1-year mortality was lower with TAVR than with surgery (14.2% vs. 19.1%; P=0.04 for superiority). The results persisted in multiple predefined subgroup analyses, including by age (> or ≤85), sex, diabetes status, and STS risk score (high vs. low). Other important 30-day outcomes included a nonsignificantly lower risk for stroke with TAVR than with surgery (4.9% vs. 6.2%) and a significantly higher risk for permanent pacemaker implantation with TAVR (19.8% vs. 7.1%).

Comment

The nonrandomized trial shows a clear survival benefit of TAVR relative to standard therapy in extreme-risk patients. The rate of pacemaker implantation is higher than with the balloon-expandable system, but the overall mortality and stroke rates are lower, and the improvement in paravalvular aortic regurgitation over time is intriguing. Determining whether these apparent advantages are truly related to device design or reflect improvements in study design (e.g., in patient selection and aortic annular sizing) would require a head-to-head device comparison.

The randomized trial in high-risk patients is a real blockbuster. A nearly 5% absolute 1-year survival advantage in a high-risk group, accompanied by a slightly lower risk for stroke, is impressive for this new TAVR technology. The lower STS risk, compared with that in the PARTNER 1A high-risk cohort, is a teaser for ongoing trials in intermediate-risk patients (PARTNER 2A and SURTAVI). PARTNER 1A demonstrated noninferiority (rather than superiority) of a balloon-expandable device relative to surgery, but I urge caution in comparing the devices given the trials' many differences (e.g., distinct risk populations, transapical vs. subclavian access, gradual improvements in sizing). Nevertheless, these two studies show that TAVR is here to stay.

  • Disclosures for Howard C. Herrmann, MD at time of publication Consultant / Advisory board Gerson Lehrman Group; Siemens; St. Jude Medical Speaker's bureau American College of Cardiology Foundation; Cardiovascular Institute; Cardiovascular Research Foundation; Christiana Medical Center; Coastal Cardiovascular Society; Crozer-Chester Hospital; Mayo Clinic; New York Cardiology Society Equity Micro-Interventional Devices, Inc. Grant / research support Abbott Vascular; Edwards Lifesciences; Gore; Medtronic; St. Jude Medical Editorial boards Catheterization and Cardiovascular Interventions; Circulation-Cardiovascular Interventions; Journal of Interventional Cardiology; Journal of Invasive Cardiology

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