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For patients with severe aortic stenosis who are not surgical candidates, transcatheter aortic valve replacement (TAVR) substantially improves health status and quality-of-life compared with standard therapy, according to a subanalysis of the PARTNER trial published online October 3, 2011, ahead of print in Circulation.

The current results, derived from Cohort B of the PARTNER (Placement of AoRTic TraNscathetER valve) trial, were previously presented in November 2010 at the American Heart Association Scientific Sessions in Chicago, IL. Earlier that year, the main trial findings were published in the New England Journal of Medicine, showing that TAVR using the Edwards Sapien device (Edwards Lifesciences, Irvine, CA) reduces all-cause mortality and repeat hospitalization compared with standard therapy but also increases major strokes and vascular complications in patients with inoperable aortic stenosis.

Led by David J. Cohen, MD, MSc, of Saint Luke’s Mid America Heart and Vascular Institute (Kansas City, MO), the new subanalysis looked at the 358 patients who were randomized to TAVR (n = 179) or standard therapy (optimal medical therapy plus balloon aortic valvuloplasty as required; n = 179). Two different measures, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Medical Outcomes Study Short-Form 12 (SF-12) Health Study, were used to assess health status and quality of life at baseline and 1, 6, and 12 months after randomization.

Substantial, Consistent Benefits from TAVR

Baseline quality of life was markedly poor for both treatment arms, including significant impairment in the ability to perform physical activities and frequent symptoms such as extreme fatigue and breathlessness.

Both groups showed increases in quality of life scores, but the TAVR group’s improvement was substantially greater. As early as 1 month post-procedure, overall KCCQ score, the study’s primary endpoint, was 13.3 points higher in TAVR patients compared with the standard therapy group (P < 0.001). Scores were 20.8 points higher in the TAVR group by 6 months and 26.0 points higher by 12 months (P < 0.001 for both comparisons), signifying a large, clinically important improvement. This benefit remained consistent across multiple subgroups identified by age, gender, surgical risk, aortic valve gradient, and COPD.

KCCQ subscales particular to symptom scores, physical limitations, quality of life, and social limitations showed similar advantages with TAVR, as did SF-12 physical and mental measures.

In addition, more patients in the TAVR group met KCCQ criteria for moderately large (≥ 10 points) and very large (≥ 20 points) health status improvement (table 1) as well as favorable (≥ 10 points plus survival) and excellent (≥ 20 points plus survival) outcome (table 2) at all time points compared with the standard therapy group.

Table 1. Improvement in Health Status^a

 ^a P < 0.001 for all time points.

Table 2. Improvement in Overall Outcome^a

^a P < 0.001 for all time points.

When quality of life was considered along with survival, the number needed to treat to obtain 1-year survival was approximately 3 with a favorable outcome and 3.5 with an excellent outcome.

Real-World Impact Explained

In a telephone interview with TCTMD, Dr. Cohen pointed out that the changes in overall KCCQ score experienced by the TAVR group were the equivalent of approximately a 2-level improvement in NYHA class, while the SF-12 improvements equaled roughly a 10-year reduction in effective age.

Another author on the study, Martin B. Leon, MD, of Columbia University Medical Center (New York, NY), also put the dramatic shift in KCCQ scores experienced by the TAVR patients into context. “A difference in 5 points is thought to be clinically significant,” he told TCTMD in a telephone interview. “By 1 year, the difference was 25, which is not mild or moderate but huge. It’s like somebody being moribund vs. somebody who’s walking around and acting normal.”

Since the majority of patients with aortic stenosis are older with potentially several comorbid conditions, Dr. Cohen said that improving quality of life is often more important than increasing survival. “What most patients are looking for is to be more comfortable and to have more enjoyment in their last few years rather than living indefinitely,” he said.

The extent of the improvement found by PARTNER surprised both Drs. Cohen and Leon. “We were concerned that, because of all the comorbid conditions, there would be a ceiling effect that would limit the quality of life benefit. That was not the case at all,” Dr. Cohen said. “The majority of patients who survived actually had very substantial benefits in terms of their symptoms and their quality of life.”

Dr. Leon was also surprised to see differences arise so early after treatment. “These patients can be so sick. A lot of them are bedridden, but I expected the recovery would take longer. It was very gratifying to see that there was fairly rapid recovery and significant symptom benefit even by 30 days,” he commented.

Worthy of More Attention

Though quality of life can be an integral part of a trial like PARTNER, Dr. Leon said that it is often overlooked. But this may soon change, he noted. “Health care economists are going to be asking not just whether patients are alive or dead, but whether you have really affected their quality of life,” he said.

With the magnitude of the results, Dr. Leon said that quality of life assessments will become more of a routine part of clinical trials in the future. “I’m very thankful to lead the effort to incorporate this in our trial, because I think it’s a key endpoint that people don’t pay enough attention to,” he said.

In a telephone interview with TCTMD, John S. Rumsfeld, MD, PhD, of the University of Colorado (Denver, CO), expressed amazement that “the quality of life results don’t seem to garner as much attention as the survival benefits for the procedure. There doesn’t seem to be quite the wow factor.”

Dr. Rumsfeld called the study clinically important, emphasizing that “the number of patients that need to get this procedure to have this kind of benefit is low and that makes it very appealing.”

Comparison with Surgery, Long-Term Follow-up Forthcoming

Another question Dr. Cohen brought up had to do with the comparison of quality-of-life improvements between TAVR patients and those who underwent surgery. These findings, from Cohort A of the PARTNER study, will be presented in November at the annual Transcatheter Cardiovascular Therapeutics symposium in San Francisco, CA, he said.

According to Dr. Leon, the US Food and Drug Administration also recently required that Edwards Lifesciences track the quality-of-life in TAVR patients formally out to 5 years to see if the benefit at 1 year shown in this study would be ongoing.

Study Details

The KCCQ consists of 23 questions addressing 5 health domains pertaining to heart failure: symptoms, physical limitation, social limitation, self-efficacy, and quality-of-life. The SF-12 combines both physical and mental measurements.

Note: Dr. Leon is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.

Source:

Reynolds MR, Magnuson EA, Lei Y, et al. Health-Related Quality of Life After Transcatheter Aortic Valve Replacement in Inoperable Patients With Severe Aortic Stenosis. Circulation. 2011;Epub ahead of print.

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• PARTNER Analysis: TAVI Substantially Improves QOL vs. Standard Therapy
• PARTNER: All-Cause, CV Mortality Lower in Patients Treated with TAVI vs. Standard Therapy at 1 Year