Aortic stenosis is common in the elderly and when symptoms arise about half of patients die within two years. Surgical aortic valve replacement is an effective therapy for aortic stenosis that can be performed with relatively low morbidity and mortality given the age and co-morbidity of most patients with aortic stenosis. However, approximately one third of patients with symptomatic aortic stenosis are considered inoperable. Until recently, there have been no effective alternative therapies to surgical aortic valve replacement for these patients.
Scientists have developed two aortic valves (Medtronics CoreValve, Edwards SAPIEN) that can be implanted using catheters rather than open-heart surgery. A large number of case-series demonstrated successful implantation of transcatheter aortic valves in more than 95% of patients, but the 30-day mortality ranged from 6% to 13%. In addition, up to 39% of patients required a permanent pacemaker, up to 28% of patients experienced major vascular complications, and up to 42% developed moderate to severe aortic stenosis. The case-series data and the small comparative studies gave inadequate information to fully understand the relative benefits and harms of TAVR compared with standard therapy.
The PARTNER B trial is the pivotal randomized trial to date that helps us understand the risks and benefits of TAVR.[51,52] In the PARTNER B trial, 179 patients with severe AS were randomized to the TAVR group (Edwards SAPIEN valve via the transfemoral approach) and 179 patients were randomized to the standard therapy group. The 30-day mortality in the TAVR group was only 5% and only 3% of the TAVR group required a permanent pacemaker. The stroke rate was higher in the TAVR group (5% versus 1%), but by one year the overall outcomes strongly favored the TAVR group. Mortality was significantly lower (31% versus 50%) and quality of life was much higher by three different instruments.
The trial was not methodologically perfect. Neither the patients nor outcome assessment was blinded. There were baseline differences between the two groups indicating that the TAVR group had a lower overall risk and fewer important comorbidities, such as COPD. Concerns have been raised because 64% of patients in the standard therapy group received aortic valvuloplasty within 30 days of randomization and an additional 20% after 30 days. However, none of these issues are of sufficient magnitude to explain the large one-year mortality difference between the two groups.
Patient selection is essential to ensure that the results of the PARTNER trial apply to patients treated in the community. All patients must be eligible for the transfemoral approach. A multidisciplinary team that includes at a minimum one cardiac surgeon, a general cardiologist, and an interventional cardiologist should agree that a patient is inoperable before offering TAVR. Patients must be informed of the upfront risk of death, stroke, pacemaker placement, and major vascular complications (16% in the PARTNER B trial). Patients also need to be informed that the long-term durability of the percutaneous aortic valves remains unclear. Observational data from one study suggest that patients who survive the first year following TAVR do well during the following year, but more data are needed. There is a high prevalence of moderate to severe AR, which may lead to recurrent symptoms or unforeseen problems with the valve. As was highlighted by Dr. Lazar in his editorial on the PARTNER B trial, given these uncertainties TAVR should not be performed in patients with a long life expectancy until more data are available. Additional studies are also needed before extending the use of TAVR to other patient groups and to other delivery approaches. Finally, as was highlighted at the Februrary 2012 CTAF meeting, the dispersion of this technology to new centers across the United States must proceed with careful thought given to training and proctoring multidisciplinary teams to become new centers of excellence. Attention needs to be paid to appropriate patient selection, their pre-operative evaluation, surgical techniques, and post-operative care in order to preserve and improve upon the results attained in the PARTNER B trial. As described under TA 5, the specialty societies are collaborating to ensure that this happens in a rational and comprehensive manner.
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