SAN FRANCISCO – Transcatheter aortic-valve implantation in high-risk patients with aortic stenosis who were not eligible for surgery reduced all-cause mortality at 2 years from 68% to 43%, compared with standard therapy, extending the positive 1-year results of a multicenter, randomized trial in 358 patients.
The 24% absolute reduction in risk of death means that four patients would need to be treated with transcatheter aortic-valve implantation (TAVI) to save one life at 2 years, compared with standard therapy, Dr. Raj Makkar and his associates reported on Nov. 10 at the Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.
Dr. Raj Makkar
The number needed to treat improved upon 1-year data presented at this meeting last year and subsequently published, which showed five patients would need to be treated to save one life at 1-year follow-up. All-cause mortality rates at 1 year were 51% on standard therapy and 31% with TAVI in the PARTNER (Placement of Aortic Transcatheter Valves) trial (N. Engl. J. Med. 2010;363:1597-1607).
Among patients who survived beyond 1 year of follow-up, all-cause mortality was halved, from 35% in the standard therapy group to 18% in the TAVI group by year 2. Overall deaths from cardiovascular causes in an intent-to-treat analysis decreased from 62% with standard therapy to 31% in the TAVI group, said Dr. Makkar, director of interventional cardiology and the cardiac catheterization laboratory at Cedars-Sinai Medical Center, Los Angeles.
"These are absolutely dramatic results. It validated and bolstered the 1-year results, an extremely positive trial," Dr. Michael Mack said at a press briefing on the study. "In this end-of-life, expensive therapy, there is a sustained benefit now out to 2 years and, hopefully, longer than that," said Dr. Mack of the Cardiopulmonary Research Science and Technology Institute, Dallas. Dr. Mack is also president of the Society of Thoracic Surgeons.
When deaths were stratified by Society of Thoracic Surgeons (STS) scores, it appeared that TAVI provided the most benefit to patients with lower STS scores who were less sick, but STS score did not affect mortality risk in the standard therapy group.
"The ultimate value will depend on careful selection of patients who are not surgical candidates and yet do not have extreme comorbidities that overwhelm the benefits of TAVI and render the intervention futile," Dr. Makkar said.
The 358-patient PARTNER trial compared TAVI with standard therapy in high-risk patients with severe aortic stenosis at 21 centers. Patients were randomized to transfemoral implantation of a balloon-expandable bovine pericardial valve (the Edwards Sapien valve) or standard therapy (including balloon aortic valvuloplasty in 84%) between May 2007 and March 2009.
The reported results applied to a prespecified cohort of patients whom surgeons considered not to be suitable candidates for surgery (cohort B). An ongoing portion of the trial is following a separate cohort of patients with high surgical risk who nevertheless were considered to be candidates for surgery (cohort A).
Based on the results from cohort B, the Food and Drug Administration approved the Edwards Sapien valve in November for the treatment of patients with aortic stenosis who are not considered candidates for surgery.
The 2-year results also showed that rates of repeat hospitalization were lower in the TAVI group at year 2 (35%), compared with the standard therapy group (72%), Dr. Makkar reported. Patients in the TAVI group gained nearly a year of days alive outside of the hospital, compared with patients given standard therapy – 699 days vs. 355.
By year 2, only 17% of patients in the TAVI group had New York Heart Association Class III or IV symptoms, compared with 58% in the standard therapy group.
Strokes were more common in the TAVI group (14%), compared with the standard therapy group (6%) at year 2. The TAVI group had higher rates of strokes than did the standard therapy group in the first 30 days after treatment and between years 1 and 2, but not between 30 days and 1 year after treatment, he said. Excess strokes in the TAVI group in the first 30 days were driven by ischemic causes, but excess strokes between years 1 and 2 were mainly due to hemorrhagic strokes, Dr. Makkar said.
The reasons for the hemorrhagic strokes appear to be multifactorial, including severe falls in three patients in the TAVI group, potential effects of medications, and other factors.
For strokes and all-cause mortality combined, 46% in the TAVI group and 68% in the standard therapy met this end point. Five patients would need to be treated with TAVI to avoid stroke or death, compared with usual care.