The prevailing wisdom is that transcatheter aortic valve replacement (TAVR) will waltz into the intermediate-risk category and then skip over to low-risk patients with severe aortic stenosis. That is, if all goes well in two randomized, controlled clinical trials in the U.S. And valves prove durable. And clinical benefits remain. And costs come down. And payers are willing to pay.
Reason for optimism
There has been a lot to make TAVR’s proponents cheer in recent months. Five-year results from the pivotal PARTNER I trial (Placement of AoRTic TraNscathetER Valves Trial) gave inoperable patients treated with Edwards Lifesciences’ balloon-expandable Sapien valve the advantage over those who underwent standard treatment, with a risk of all-cause mortality at five years of 71.8 percent for TAVR vs. 93.6 percent for surgery. Half a decade after implant, the valves showed no signs of deterioration with durable hemodynamics. Pop over to the high-risk patients, and all-cause mortality at five years was similar for TAVR and surgery and TAVR patients had lower stroke rates in an intention-to-treat analysis.
Bookend those results with two-year data from another pivotal randomized clinical trial, this one for Medtronic’s self-expanding Core-Valve device in high-risk patients. This time TAVR emerged as superior, with all-cause mortality rates of 22.2 percent for TAVR vs. 28.6 percent for surgery; stroke rates of 10.9 percent vs. 16.7 percent; superior hemodynamics; and no structural valve failures.
In a subgroup of CoreValve patients with Society of Thoracic Surgeons (STS) risk scores of 7 or less, the survival gap widened by more than 11 percentage points. Yet another trial that captured results on intermediate-risk patients with an average STS score of 5.3—in this case using Edwards’ lower-profile Sapien 3 valve—reported a 30-day all-cause mortality rate of 1.1 percent, an all-stroke rate of 2.6 percent and a disabling-stroke rate of 1 percent. Although single-arm and nonrandomized, the ultra-low rates fueled the buzz at the 2015 American College of Cardiology’s (ACC) scientific sessions in San Diego, where the other TAVR studies also were unveiled.
“We know in high risk we can achieve at least equivalent if not superior survival,” says Michael J. Reardon, MD, a cardiothoracic surgeon at Houston Methodist Hospital in Texas, who as CoreValve’s principal investigator presented the two-year results at ACC.15 on March 15. Reardon also is the co-principal investigator for SURTAVI, Medtronic’s ongoing randomized trial in intermediate-risk patients, and REPRISE III, Boston Scientific’s trial for the Lotus TAVR system in extreme- and high-risk patients.
“It seems fairly reasonable that we will achieve something very similar in this intermediate risk,” he adds. “We know these valves give us hemodynamics that are as good as or better than surgical valves. That will not change according to your risk category. We know that in high risk there are no more strokes now than in heart surgery and there is no reason to think that will change as we go down.”
What will change, if TAVR’s indication expands to include intermediate- and low-risk patients, is the number of potential candidates for a procedure. One meta-analysis estimated the rate of severe aortic stenosis in adults 75 years old and older was 3.4 percent (J Am Coll Cardiol 2013;62:1002–1012). The rate for aortic stenosis—those possible TAVRs-to-be if their disease progresses—was 12.4 percent. The authors calculated that under the current indications, more than 91,000 people in the U.S. qualified for TAVR, with 8,205 more joining the ranks annually.
Speaking at the 2015 Transcatheter Valve Therapies conference in Chicago in early June, Martin B. Leon, MD, director of the Center for Interventional Vascular Therapy at NewYork Presbyterian/Columbia University Medical Center in New York City, emphasized the unmet need in this population. “The majority of U.S. patients with severe AS [aortic stenosis] who are symptomatic are untreated,” he says. “They don’t get either surgery or TAVR. The estimate is that the prevalence of severe AS is about half a million and between surgery and TAVR in 2014, less than 100,000 were treated. There is a tremendous potential for further growth, just in the U.S. alone.”
Supply and demand
The marketing analytics firm GlobalData projected that the compound annual growth rate for TAVR valves will increase 19.7 percent between 2013 and 2020, expanding the market from