Monday, August 27, 2012

TAVR: Life-prolonging and palliative or risky and costly?



Transcatheter aortic valve replacement (TAVR) is a therapy proposed “as the standard of care for symptomatic patients with aortic stenosis (AS) who do not have reasonable surgical alternatives” in the recent report of the 2 year outcomes from the Placement of AoRTic TraNscathetER Valve (PARTNER) trial which compared TAVR to standard medical therapy.  Proponents of TAVR suggest that this procedure provides a non-surgical alternate intervention for frail elderly patients who have life-limiting, symptomatic AS. Geriatric and palliative care practitioners need a working understanding of the potential risks, benefits and burdens of TAVR, especially for vulnerable older adults with multimorbidity.

In a recent geriatrics journal club, we summarized the 1 year and 2 year outcomes from the PARTNER trial as follows:

Of 3105 patients screened, 12% (358 patients) were randomized to transfemoral TAVR vs Standard Rx. In Standard Rx, 82.3% underwent balloon valvuloplasty. This efficacy trial was funded by Edwards Lifesciences, the maker of the SAPIEN heart-valve system used in the study. Mean age was 83. Despite randomization, the Standard Rx group had significantly more COPD, atrial fibrillation, and fraility.

Key results:

  1. Death from any cause at 2 years was lower in the TAVR group (TAVR 43.3% vs Standard Rx 68.0%). Since the absolute risk reduction was 24.7%, four TAVR procedures would prevent one death over 2 years.
  2. Complications in the TAVR group included increased rates of stroke (8.3% increased risk at 2 yrs), major vascular complications (14.6% at 1 yr), and major bleeding (11.1% at 1 yr) compared to Standard Rx.
  3. Medical care utilization by Standard Rx included increased rates of valve-related rehospitalization (37.5% increased rate at 2 yrs), balloon aortic valvuloplasty (82.5% at 2 yrs) and aortic valve replacement (8.0% at 2 yrs) compared to the TAVR group.
  4. TAVR recipients had significantly improved NYHA class and greater median number of days alive and out of the hospital (TAVR 699 days vs Standard Rx 355 days). 6 minute walk distance was noted to be improved (data incomplete).
  5. Patients with greater surgical risk based on the Society of Thoracic Surgeons (STS) Risk Score 15% who underwent TAVR did not have a significant mortality benefit.


How might the results of the PARTNER trial apply to frail older adults with multimorbidity?

As with any efficacy trial, we first ask how similar our patient is to the trial participant. The PARTNER trial included only 12% of those screened. Key exclusions were patients with coronary disease requiring treatment and severe peripheral vascular disease. While the TAVR group showed an overall mortality benefit, the TAVR group randomly had less COPD and frailty. There was diminished benefit after TAVR for patients with greater surgical risk based on the STS score. Predictors of 2 yr mortality after TAVR include prior stroke [HR 2.99 (95% CI 1.19 to 7.51)] and O2-dependent COPD [HR 1.69 (95% CI 1.05 to 2.73)]. TAVR was associated with higher rates of stroke, bleeding and vascular complications. A recent BMJ review critiquing TAVR and specifically the PARTNER trial noted that “the PARTNER trial seems to have important problems, the most relevant being publication bias and lack of data transparency, unbalanced patient characteristics, and incompletely declared conflicts of interest.”

From a geriatrics and palliative care perspective, we still need more information regarding the impact of TAVR on essential clinical measures such as functional status, health-related quality of life, symptoms, post-acute care utilization, and which aspects of frailty might be reversible. An analysis of 1 year outcomes after TAVR vs Standard Rx reported that health status was improved after TAVR compared to Standard Rx. I wonder how gait speed, cognitive impairment, depression, falls and other issues important to seniors are affected.

Thus, in real-world situations, I find it difficult to know what benefits of TAVR I can expect, and for which patients. Will my patient with multimorbidity receive the significant mortality benefit and symptomatic improvement? As with left ventricular assist devices (LVADs) for advanced heart failure, we are again faced with technology that may reverse some aspects of frailty, but we don’t know which parts of frailty. Additionally, even TAVR in the clinical trial setting had a sobering 43% absolute mortality at 2 years. From my perspective, there is a need to discuss goals of care, quality of life preferences, and expectations before a TAVR is performed.

What do you think: Should patients being considered for TAVR be routinely referred for palliative care consultation? Has the availability of TAVR impacted your geriatrics or palliative care practice? Have you seen significant functional or quality of life improvements in your patients after TAVR?

Post-script: Estimated costs from the PARTNER trial
Procedure: $42 806
Hospitalization: $78 542
Follow-up through 12 months: $29 289 (TAVR); $53 621 (Standard care)
Cumulative 1-year costs: $106 076 (TAVR); $53 621 (Standard care)


By: Hillary Lum (@hdaylum)

9 comments:

Anonymous said...

My grandmother was a candidate for a transcatheter aortic valve replacement, for a different study than PARTNER. She had significant cognitive decline but physically was a good candidate for the procedure, and she probably would have made the trial numbers look good.

The cardiac team that evaluated her accepted her for the study but, bless them, raised a red flag about whether the surgery was in her best interest given her mental status. That confirmed family concerns and the two with medical power of attorney declined to go through with it.

My grandmother passed away recently, a bit more than a year after the surgery debate. As a family member, I am very grateful that we had the support of her medical team in declining to have her heart outlive her mind. (A previous cardiac surgeon was not nearly as understanding a few years earlier when open-heart valve replacement was declined because of family concerns that she was too frail to recover well.)

Anonymous said...

The "right" study looking at TAVR hasn't been yet, at least from my vantage as a Geriatrician. I believe that, clinically, the two cut points (one "between" open surgery versus TAVR as one, and the other between TAVR and no treatment due to futility) necessary to understand "what to recommend" for the patient with severe AS don't really exist yet. Frailty in an FI model (taking into account multi-morbidity, cognition, nutrition, etc., in addition to the physical phenotype) intuitively seems most likely to provide those cut points; yet, the study hasn't been done.

Pursuing Palliative Care or Geriatric consultation for these folks is good for business, but without some math-based score to assess (again, I would argue that the FI is likely to be best) is just more muddle in a very difficult decision process. Besides, the oversight for the interventional Cards and CT surgeons is so intense, and they're under such pressure to identify the likely-futile cases pre-op already that another consultation is not likely to benefit the patient, at least in my opinion.

Laura Hanson said...

At the University of North Carolina we also reviewed this study in Journal Club. The control condition is described as "standard care," but included balloon aortic valvuloplasty for 63.7%. Patients in the control group did not receive optimal supportive care or careful symptom management for aortic stenosis -- this would be the optimal control condition to test a new procedure.

Dan Matlock said...

I think we should put TAVR squarely in the bucket of expensive, aggressive things that may have small benefits for some patients. Along with LVADs, ICDs, and many 4th line chemos...

To that end, these are the things we need to very frank discussions about in this country...

Alex Smith said...

Thanks for sharing this review Hilary. It does seem that there is a small select group of patients who may on balance benefit more than be harmed. But the concern is that physicians, patients, and TAVR-makers will get carried away and start using this willi-nillie. We've seen it before (ICDs).

The concept of aortic stenosis as a geriatric condition isn't so new, but conceptualizing it as a palliative condition is somewhat new. Torrey Simons at Stanford and the Palo Alto VA is doing interest work in decision making in this area, funded by the National Palliative Care Research Center.

See http://www.npcrc.org/grantees/grantees_show.htm?doc_id=1635637

Anonymous said...

I find it interesting that the standard care group received balloon valvuloplasty, which is certainly not standard of care anymore.

Bruce Scott said...

Digging up an old topic, but we had a cardiologist in today at my geriatrics educational session, so I'm riled up. He was quite pro-TAVR. He did not believe that the company had suppressed negative data, and suggested that I must have been wrong about it.

You've linked to one of the BMJ critiques above, but it is behind a paywall. (BMJ 2012, Van Brabandt, Transcatheter aortic valve implantation (TAVI): risky and costly.) Here is a short quotation from the article, which highlights the profoundly unethical behavior and academic dishonesty of the company involved:

"But even this conclusion is thrown into doubt by a follow-up study authorised by the FDA, in which 41 inoperable patients were randomised to TAVI and 49 to standard therapy. This study remains unpublished, and our attempts to gain access to further details have been rebuffed by the FDA and the study sponsor. But the data presented at an FDA meeting on 20 July 2011 showed that the TAVI patients fared worse than those given standard therapy (one year mortality 34.3% v 21.6%).15

We have repeatedly sought access to further details of this follow-on trial, carried out under FDA auspices as a formally approved “continued access study,” the purpose of which is to enable sponsors of clinical investigations to continue to enrol patients while a market application is being sought. The FDA responded that any further data analysis of a premarket application is proprietary information and that it was up to the sponsor to release it, if so inclined. But our requests to the sponsor (Edwards) and the principal investigator went unanswered. In our view, this behaviour is both ethically and scientifically unacceptable and should be legally regulated in future. Study sponsors should be obliged to make the results of a negative trial public so that policy makers can reach rational and balanced decisions.

Given our failure to make progress with the FDA or the sponsor, we approached the NEJM which had published the PARTNER trial. We put our objections to the NEJM, which passed them on to the investigators. Their response convinced the NEJM editors that “while each of the points we raised deserved a thoughtful review, they did not, either individually or together, fundamentally place the findings of the PARTNER trial in serious doubt.” Asked what the responses of the investigators had been, NEJM responded that it had not requested permission from them to pass them on, since they were intended for its own confidential evaluation. We were recommended to request this information directly from the study sponsor, which we did, to no avail.

NEJM has, however, published two year follow-up results that essentially confirmed the one year data.16 17 However, it did so without demanding that the study sponsor publish or discuss the negative results of the follow-on trial. It is difficult to understand this decision."

Anonymous said...

My elderly (80) mother was approved for the TAVR procedure. She had COPD and Diabetes. While the actual TAVR procedure went smooth (as far as I was informed), her recovery was not so smooth. She battled blood pressure and respiratory problems. After a few days of relative stability in the ICU, she suffered a mild cardiac arrest. Fortunately, a staff nurse was with her and their instant response got it under control. After a few more days of stability, she was transferred to a "step down" unit for further recovery. A couple days after that, she suffered fatal cardiac arrest. I don't in any way fault the medical care she received or the facility, as from what I observed, they were completely professional, caring and organized at what they were doing. We knew my mother was in terrible condition before the operation and were hoping the TAVR procedure would "buy" her a couple or more years.
This experience will live with me forever, as it was my final "OK, Mom, I think it's the right thing" when she wanted to know what I thought. I know it's not my fault she passed away, but there is a small, little part of me that feels guilty. If she would have decided to do nothing - she may still be alive. We'll never know.
I guess what I'm trying to say, is that TAVR-approved patients should understand that the only reason they got approved is that they really are in terrible physical condition. I apologize that my post is not medically technical - I just stumbled on this blog and saw an opportunity to post the experience I had. I wish any and all that undergo the TAVR procedure the very best of luck!

Alex Smith said...

Thank you anonymous for sharing the story about you and your mother. These decisions are not easy, and even with easy decisions sometimes things don't go the way we hope.