Some practitioners, such as the PARTNER investigators, are advocating that transcatheter aortic valve implantation (TAVI) become the new standard of care for patients with aortic stenosis who are not suitable surgical candidates. However, others question whether the quality of life, practice management, cost effectiveness and ethical considerations of treating such sick patients have been answered definitively before it becomes routine clinical practice in the U.S.
Approximately 30 percent of U.S. patients with aortic stenosis (AS) who have symptoms are not being treated with surgery—due to extreme age, comorbidities or poor heart function. Currently, transcatheter aortic valves, which could present an alternative for this population, are investigational devices in the U.S., while several have been approved in Europe since 2007.
At TCT10, Martin B. Leon, MD, director of the Center for Interventional Vascular Therapy at New York Presbyterian Hospital/Columbia Medical Center in New York City, presented the much-anticipated results of the PARTNER trial (N Engl J Med 2010;363:1597-1607).
In the study, investigators randomly assigned 358 patients with AS, whom surgeons determined to be unsuitable for surgery, to standard therapy or TAVI of a balloon-expandable bovine pericardial valve (Sapien, Edwards Lifesciences). The patients underwent randomization at 21 centers (17 in the U.S.) in two arms of 179 patients. The primary endpoint was the rate of death from any cause. The average age of these patients was 83 years, with 20 percent at more than 90 years.
At 30 days, the rate of all-cause mortality was 5 percent in the TAVI arm compared with 2.8 percent in the standard therapy arm. At one year, the rate was 30.7 percent with TAVI compared with 50.7 percent with standard therapy, which confirms the “dire natural history” of patients with untreated AS, says Leon, adding that these results suggest only five patients need to be treated to save a life.
The rate of repeat hospitalization was 5.6 percent at 30 days and 22.3 percent at one year in the TAVI arm, compared with 10.1 percent at 30 days and 44.1 percent at one year in the standard therapy arm.
In the year after TAVI in PARTNER, there was no deterioration in the functioning of the valve, as assessed by evidence of stenosis or regurgitation on an echocardiogram. However, valve durability is an important consideration. “While the median follow-up time for PARTNER was 1.6 years, valve durability needs to be considered out to five, 10 and 15 years,” Leon says, “so the patients require careful follow-up with echocardiograms to ensure that these valves are as durable as surgical valves.”
Despite the promising mortality and repeat hospitalization rates, the TAVI arm experienced higher complication rates. At 30 days, TAVI, compared with standard therapy, was associated with higher incidence of major strokes (5 vs. 1.1 percent) and major vascular complications (16.2 vs. 1.1 percent). At one year, TAVI also was associated with higher incidence of major strokes (7.8 vs. 3.9 percent) and major vascular complications (16.8 vs. 2.2 percent).
While Leon says the stroke outcomes were expected based on the European registries, he suggests that the next generation of devices may help reduce the frequency of procedure-related complications. “In these older patients with vascular disease, it is difficult to insert the larger device used in the PARTNER trial,” he says. “We’re hoping that the next-generation devices, such as the Sapien XT [Edwards] that is 40 percent smaller and more durable or the EU-approved CoreValve [Medtronic], will obviate the vascular complications and reduce the bleeding complications.”
In December 2010, Medtronic commenced its U.S. pivotal trial designed to evaluate the safety and efficacy of the CoreValve system. The study will seek to enroll more than 1,300 patients at 40 clinical sites. The trial includes two studies in different patient populations: one study of patients diagnosed as high risk for aortic valve surgery and a second study of patients diagnosed as extreme risk. Patients deemed at extreme risk will not be randomized to optimal medical management; rather, they will be evaluated against a performance goal derived from contemporary studies. Patients in the high-risk group will be randomized one-to-one to either TAVI with CoreValve or to surgical aortic valve replacement (SAVR). The primary endpoint will be all-cause death or major