With transcatheter aortic valve replacement (TAVR), proper patient selection plays a key role in successful outcomes. It may prove to be a linchpin in reimbursement decisions as well.
In November 2011, TAVR hit the ground running in the U.S. with the FDA’s approval of the Sapien aortic valve in inoperable patients with symptomatic aortic stenosis. Less than a year later, the agency gave it another boost by including high-risk patients. The momentum continued into 2013 with encouraging results from the pivotal CoreValve Extreme Risk Iliofemoral study, presented in late October at the Transcatheter Cardiovascular Therapeutics scientific session in San Francisco.
Just as PARTNER (Placement of AoRTic TraNscathetER Valve Trial) data provided the evidence base for approval of Edwards Lifesciences’ Sapien valve, CoreValve Extreme Risk findings may pave the way for commercialization in the U.S. of Medtronic’s CoreValve. The 12-month results—with higher survival and lower stroke rates than in PARTNER—prompted the FDA to announce it would not convene an advisory panel to help it reach a decision on the device’s safety and efficacy. The decision is expected sometime this year.
Patient selection, crucial in clinical trials, is likely to remain a critical factor in the continuing rollout of TAVR, too.
In TAVR, the lines between risk groups can become blurred, particularly at the upper and lower boundaries, according to cardiac surgeons who participated in the two trials. And the grimmest of the gray areas may be inoperable patients with severe aortic stenosis who will die if left untreated but who will not benefit from treatment, either. Michael J. Mack, MD, a PARTNER investigator and medical director of cardiovascular surgery of the Heart Hospital Baylor Plano in Texas, describes these as “the toughest clinical decisions we are making: who is not a candidate for a TAVR because they are too old, too debilitated, too frail and despite the fact that they would get a successful procedure, are not going to have a significant survival benefit.”
These patients may have comorbidities such as severe chronic obstructive pulmonary disease and renal failure in addition to aortic stenosis, says Michael J. Reardon, MD, a cardiothoracic surgeon at Houston Methodist DeBakey Heart & Vascular Center in Texas and a CoreValve investigator. “I fix your valve but you still are so sick from your bad lungs and your bad kidneys that you don’t get better,” he says.
With years of experience, cardiovascular specialists are getting better at recognizing factors that contribute to futility and a poor outcome. Mack lists a Society of Thoracic Surgeons (STS) predicted operative risk score in the high teens to low 20s, significant renal disease, frailty, being wheelchair bound and being on home oxygen as flags that help identify some patients who are not good TAVR candidates. “It is trying to determine where that upper boundary is between patients who are dying with aortic stenosis vs. those who are dying from aortic stenosis,” he says.
David Cohen, MD, a cardiologist and medical director of the Medical Economics and Technology Assessment Group at Mid America Heart Institute in Kansas City, Mo., adds that physicians should consider quality of life as well as survival when choosing TAVR patients, a perspective shared by Mack and Reardon. Patients in their 80s are more likely to be concerned about quality issues such as independence during the period left in their lives than would a younger person, the thinking goes.
“We believe they [survival and quality of life] are both important and different patients may value the different endpoints differently, depending on their circumstances and priorities,” says Cohen, who has conducted analyses in both trials. “That is why we advocated for endpoints that included both survival and a good quality of life as being optimal for patients after TAVR.”
Using CoreValve Extreme Risk data and quality of life tools, Cohen and his colleagues identified predictors of a good or poor outcome. Preliminary data showed that being wheelchair bound, on home oxygen, having a low albumin, a higher STS mortality risk score, a previous bypass operation and a low aortic valve gradient were associated with a worse outcome at six months. He adds that categories such as frailty and disability were more important than individual factors, the research was preliminary and predictors might change as researchers gather more data.