SAN FRANCISCO – Among patients with severe aortic stenosis at low surgical risk, both transcatheter and surgical aortic valve replacement resulted in substantial health status benefits at 1 year despite most patients having New York Heart Association class I or II symptoms at baseline.
However, when compared with surgical replacement,
The findings come from an analysis of patients enrolled in the randomized PARTNER 3 trial, which showed that transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve. At 1 year post procedure, the rate of the primary composite endpoint comprising death, stroke, or cardiovascular rehospitalization was 8.5% in the TAVR group and 15.1% with surgical aortic valve replacement (SAVR), for a highly significant 46% relative risk reduction (N Engl J Med 2019 May 2;380:1695-705).
“The PARTNER 3 and Evolut Low Risk trials have demonstrated that transfemoral TAVR is both safe and effective when compared with SAVR in patients with severe aortic stenosis at low surgical risk,” Suzanne J. Baron, MD, MSc, said at the Transcatheter Cardiovascular Therapeutics annual meeting. “While prior studies have demonstrated improved early health status with transfemoral TAVR, compared with SAVR in intermediate and high-risk patients, there is little evidence of any late health status benefit with TAVR.”
To address this gap in knowledge, Dr. Baron, director of interventional cardiology research at Lahey Hospital and Medical Center in Burlington, Mass., and associates performed a prospective study alongside the PARTNER 3 randomized trial to understand the impact of valve replacement strategy on early and late health status in aortic stenosis patients at low surgical risk. She reported results from 449 low-risk patients with severe aortic stenosis who were assigned to transfemoral TAVR using a balloon-expandable valve, and 449 who were assigned to surgery in PARTNER 3. At baseline, the mean age of patients was 73 years, 69% were male, and the average STS (Society of Thoracic Surgeons) Risk Score was 1.9%. Rates of other comorbidities were generally low.
Patients in both groups reported a mild baseline impairment in health status. The mean Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS) score was 70, “which corresponds to only New York Heart Association Class II symptoms,” Dr. Baron said. “The SF-36 [Short Form 36] physical summary score was 44 for both groups, which is approximately half of a standard deviation below the population mean.”
As expected, patients who underwent TAVR showed substantially improved health status at 1 month based on the KCCQ-OS (mean difference,16 points; P less than .001). However, in contrast to prior studies, the researchers observed a persistent, although attenuated, benefit of TAVR over SAVR in disease-specific health status at 6 and 12 months (mean difference in KCCQ-OS of 2.6 and 1.8 points respectively; P less than .04 for both).
Dr. Baron said that a sustained benefit of TAVR over SAVR at 6 months and 1 year was observed on several KCCQ subscales, but a similar benefit was not noted on the generic health status measures such as the SF-36 physical summary score. “That’s likely reflective of the fact that, as a disease-specific measure, the KCCQ is much more sensitive in detecting meaningful differences in this population,” she explained. When change in health status was analyzed as an ordinal variable, with death as the worst outcome and large clinical improvement, which was defined as a 20-point or greater increase in the KCCQ-OS score, TAVR showed a significant benefit, compared with surgery at all time points (P less than .05).
In an effort to better understand the mechanism underlying this persistent albeit small late benefit in disease-specific health status with TAVR, the researchers generated cumulative distribution curves to display the proportion of patients who achieved a given change on the KCCQ-OS. A clear separation of the curves emerged, with 5.2% more patients in the TAVR group experiencing a change of at least 20 points, compared with the surgery group. “This suggests that the difference in late health status between the two groups is driven by this 5.2% absolute risk difference in the proportion of patients who experienced a large clinical improvement,” Dr. Baron said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Next, the researchers performed subgroup analyses to examine the interaction between the 1-year health status benefit of TAVR over surgery and prespecified baseline characteristics including age, gender, STS risk score, ejection fraction, atrial fibrillation, and New York Heart Association (NYHA) class. They observed a significant interaction between NYHA class and treatment effect such that patients who had NYHA class III or IV symptoms at baseline derived greater benefit from TAVR, compared with those who had NYHA class I or II symptoms at baseline.
“This finding suggests that it’s the patients with worse functional impairment at baseline who may be that subset of patients on the cumulative responder curves who gained better health status outcomes with TAVR, compared with surgery in the low-risk population,” Dr. Baron said.
Suzanne V. Arnold, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo., who was an invited discussant, said that it was “remarkable” that patients in the substudy were not particularly symptomatic and yet they still experienced close to a 20-point improvement in the KCCQ-OS score following TAVR, and asked whether frailty may have played a role in the 1.8-point adjusted difference in the KCCQ-OS score between TAVR and surgery at 1 year. Dr. Baron responded that she and her colleagues performed a subgroup analysis of patients who had two or more markers of frailty versus those who had one or less. Noting that there were only 20 patients in that subgroup, she said there was a significant signal that patients who were considered have two or more frail measures were considered to do much better with TAVR.
Dr. Baron concluded that the study’s overall findings, taken together with the clinical outcomes of the PARTNER 3 trial, “further support the use of TAVR in patients with severe [aortic stenosis] at low surgical risk. Longer-term follow up is needed (and ongoing) to determine whether the health status benefits of TAVR at 1 year are durable.” The content of the study was published online at the time of presentation (J Am Coll Cardiol 2019 Sep 29. doi: 10.1016/j.jacc.2019.09.007). The PARTNER 3 quality of life substudy was funded by Edwards Lifesciences. Dr. Baron disclosed research funding and advisory board compensation from Boston Scientific Corp and consulting fees from Edwards Lifesciences.