TAVR Improves Health Status Over Surgery in Low-Risk Patients at 1 Year: PARTNER 3 – TCTMD

SAN FRANCISCO, CAAmong patients with severe aortic stenosis at low surgical risk, TAVR is associated with improved disease-specific health status over SAVR at not only 1 month but also 6 and 12 months, according to a PARTNER 3 substudy.

Despite the fact that patients werent overly symptomatic at baseline, these patients still saw a large improvement in quality of life, Suzanne J. Baron, MD (Lahey Hospital and Medical Center, Burlington, MA), told TCTMD. So even in the low-risk population, there is a huge value from a patient-reported outcomes standpoint with [TAVR]. Baron presented the findings today in a late-breaking clinical trial session here at TCT 2019.

Another take-home message from this analysis, which was simultaneously published in the Journal of the American College of Cardiology, is that the small but sustained improvement observed with TAVR over SAVR through 1 year represents a significant benefit for a subset of patients, Baron said, noting that these are likely patients who are more symptomatic at baselinewith NYHA class III or IV symptoms.

Its information that a clinician can use for patients in whom you are trying to decide [if TAVR or SAVR] is the right way to go, she explained. In some cases it's very clear. If a patient has a huge calcium shelf, then surgery is going to be the better way for them, fine. But for patients where it's really borderline, the clinician takes a look and says the patient is . . . a little more frail, a little more symptomatic, maybe that is the patient that going to do better with TAVR from a health status outcomes standpoint.

A lot of these patients may still be working and caring for grandkids or elderly parents. It becomes a lot more of an issue. Suzanne J. Baron

To TCTMD, Philippe Gnreux, MD (Morristown Medical Center, NJ), who was a panelist in press conference yesterday, said these results will be helpful for physician conversations with patients. [But] I can tell you that the discussion is very brief because patients are asking for [TAVR]. Its not a very big sell to not have a chest opened in terms of quality of life. We see a lot of healthy patients, 60 years old, that want to go back to work next week. That's what is driving the discussion, he explained.

Until now, much of the focus for low-risk TAVR has been on hard outcomes like death, MI, stroke, and rehospitalization, Baron added.

However, patient-reported outcomes are incredibly important, too, she said. I've got plenty of patients who say, I don't mind if I die, but please, I do not want a stroke because I do not want to live like that. . . . A lot of these patients want to get back to what they're doingthey want to be able to interact with their familiesand in the low-risk populations it's even more important. A lot of these patients may still be working and caring for grandkids or elderly parents. It becomes a lot more of an issue.

Large Benefit in Small Proportion

As reported by TCTMD, the PARTNER 3 trial demonstrated that TAVR with the balloon-expandable Sapien 3 transcatheter heart valve (Edwards Lifesciences) was better than surgery for the prevention of death, stroke, and rehospitalization at 1 year. PARTNER 3 included 1,000 patients with an STS Predicted Risk of Mortality of less than 4% (mean score 1.9%) treated at 71 centers. The average age of those treated was 73.4 years, and nearly 70% of patients were men.

In this substudy, Baron and colleagues used the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score (ranging from 0 to 100) to assess health status outcomes through 1 year in both study groups. The mean baseline KCCQ overall summary score was 70 for both TAVR and SAVR patients, which corresponds to NYHA class II symptoms.

As expected, TAVR patients demonstrated substantially improved health status at 1 month. Baron reported that, unlike in earlier studies, the benefit of TAVR over surgery persisted through 6 (2.6-point difference; P = 0.002) and 12 months (1.8-point difference; P = 0.03), although the magnitude was smaller. at 1 year, both groups had experienced an increase of about 19 points from baseline, which is consistent with a large clinical improvement.

The findings were confirmed on several KCCQ subscales, but no difference was observed in health status outcomes at 1 year on generic measures like the SF-36 physical and mental summary scores. Baron said this was likely reflective of the fact that as a disease specific measure, the KCCQ is much more sensitive at detecting meaningful differences in this population.

When change in health status was analyzed as an ordinal variable with death as the worst outcome and a large clinical improvement defined as a greater than 20-point increase in the KCCQ overall summary score, TAVR demonstrated a significant benefit compared with surgery at all time points.

To further explore the mechanism of the benefit observed in this study, the researchers generated cumulative distribution curves to determine the proportion of patients achieving various changes in KCCQ overall summary score at 1 year. There was a clear separation of the curves with more TAVR patients experiencing a change of 20 points or greater when compared with surgery, Baron reported, adding that the difference in late health status between the two groups was driven by the 5.2% absolute risk difference in the proportion of patients who experienced a large clinical improvement.

Prespecified subgroup analyses showed no difference in KCCQ overall summary score for TAVR vs SAVR by age, gender, STS risk score, ejection fraction, and A-fib, but there was a significant interaction between baseline NYHA class and treatment effect with patients who had NYHA class III or IV symptoms at baseline deriving greater benefit from TAVR than those categorized as NYHA class I or II (P = 0.020 for interaction).

Additionally, on exploratory analyses to determine whether differences in periprocedural complications between the groups could explain the observed health status benefit, Baron and colleagues found a 1.8-point adjusted difference in KCCQ overall summary score between TAVR and SAVR at 1 year. This treatment effect was mildly attenuated when 30-day complications were added to the model, but a 1.3-point difference in the KCCQ overall summary score remained in favor of TAVR. It suggests that periprocedural complications play a partial role but not a full role in the sustained health benefits, Baron said.

Frailty, Complications May Matter

In a media briefing, Suzanne Arnold, MD (Saint Lukes Mid America Heart Institute, Kansas City, MO), noted two really remarkable aspects about the substudy. The first is that the patients were not particularly symptomatic going into this and yet still had a nearly 20-point improvement post-TAVR, she said. [This] may speak to the aspect that KCCQ is very disease-specific and these patients don't really have a lot of other comorbidities that are going to potentially impact their health status.

Secondly, Arnold commented that while a two-point increase is not a large benefit per se, those cumulative response curves are really interesting because I think it highlights that small percentage of patients who seem to get a larger benefit. As to why this might be, whether there are particular subgroups or complications driving this benefit, Arnold said its unclear, but its possible that frailty might play a role.

Frail patients were not included in PARTNER 3, but was there any signal of prefrail patients that may not have a lot of comorbidities but may have some mobility deficit that might have impacted their ability to recover from the surgery? she asked.

Baron replied that some frailty measures were collected in the overall trial but no participants met the criteria for overall frailty. We did do a subgroup analysis on patients who had two or more markers of frailty versus those that had one or less, she said, noting that only 20 patients were included. We did see a significant signal that patients who were considered to have two or more frail measures were considered to do much better with TAVR. It does make you think that is there something about the NYHA class that a clinician takes a look at a patient and just from that eyeball test says this patient just doesn't look functionally great. . . . Maybe it's those patients who are going to do a little bit better with TAVR vs surgery with all other things being equal.

Juan Granada, MD (Cardiovascular Research Foundation, New York, NY), who moderated the media briefing, commented on the evolution of TAVR from inoperable to low-risk patients and the associated economic implications. What has been the evolution throughout the years in terms of the financial impact for hospitals and centers according to the risk of the patient? he asked, addressing the panel.

When you deal with very sick patients, they stay longer in the hospital, which costs more, Gnreux replied. Now, were dealing with less-sick patients, but we've become very efficient and [have] less complications. . . . The rate of rehospitalization is lower, so weve become much more cost-effective, and with all the new tools that are coming that may increase the cost of the procedure, we reduce the complications [further].

Baron added that no data are available yet on cost-effectiveness of low-risk TAVR, but we do know that when weve compared inoperables versus high-risk versus intermediate-risk, we've seen that the procedure becomes substantially more cost-effective even so that in the intermediate-risk population it was actually cost saving. A lot of this has been driven by decreasing rates of complications, but more importantly, decreasing length of stay in the hospital associated with TAVR.

The big message is the trend continues to be the same, Granada summarized. One of the things that I really think is going to be determined in the future is the impact of technological improvements and procedural experience on cost, because at the end of the day what is going to drive cost . . . is how many patients need to come back for reevaluation and paravalvular leak treatments. If the technology continues to improve and those signals start to disappear then it's going to really start to do even better, . . . but time will tell.

Baron told TCTMD that they will continue to follow these patients out to determine long-term outcomes. Durability is going to be the key both for hard outcomes, for how well the valve is functioning, and all patient reported outcomes, she said. I don't have a reason to think that this benefit wouldn't sustain past a year, because again people are recovered from the procedure, so if it's there at a year, I don't know why it wouldn't necessarily be there at 2 years, 3 years, and 4 years, assuming that there's no difference in health durability. But we're going to get those answers.

Note: Several co-authors are faculty members of the Cardiovascular Research Foundation, the publisher of TCTMD.

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TAVR Improves Health Status Over Surgery in Low-Risk Patients at 1 Year: PARTNER 3 - TCTMD