While percutaneous aortic valve replacements have been performed for more than six years in Europe, the option is not available to U.S. patients with severe aortic stenosis (AS) who are not surgical candidates, except for the select few enrolled in the Edwards Lifesciences PARTNER trial. With Medtronic applying for an FDA investigational device exemption (IDE), and a few other players emerging in Europe, the market seems explosive, but many clinical, ethical and financial questions need to be addressed before this therapy becomes a standard part of clinical practicein the U.S.
Where are we now?
Patients with severe symptomatic AS who are not operative candidates have an “extremely poor” prognosis, with survival rates as low as 50 percent at two years and 20 percent at five years after symptom onset (Heart 2000; 84;211-218). After the development of left ventricular failure, life expectancy is slightly greater than one year.
There remain no medical therapy options for the disease state. And along with the high risk of mortality, the “mode of death is horrible,” says Martin B. Leon, MD, an associate director of the Center for Interventional Vascular Therapy at New York Presbyterian Hospital/Columbia University Medical Center in New York City. “The patients often have recurrent rehospitalization, congestive heart failure, chest pain, fainting spells—it is a terrible way for a patient to die,” he adds.
Despite these concerns, many patients still are not referred for surgical treatment—which is the only approved treatment in the U.S. Only about 45 percent of patients with AS are referred for surgical aortic valve replacement (AVR) (Eur Heart J 2003;24:1231–1243). And, there remains a subset of patients who are not surgical candidates.
“Higher risk, elderly [older than 75 years] patients with severe AS have been widely undertreated,” says Eberhard Grube, MD, director of the department of cardiology at Heart-Center Siegburg in Germany, who has been utilizing the CoreValve transcatheter device in Europe for several years.
Yet, the newer transcatheter approach has arisen as a viable clinical option for these patients who are considered inoperable. In Europe, Medtronic’s CoreValve and the Edwards’ Sapien valve have regulatory approval. Meanwhile, two second-generation devices with smaller sheath sizes from Direct Flow Medical and Sadra Lotus are currently undergoing European trials. In the U.S., Edwards was granted an IDE for the ongoing PARTNER trial, and Medtronic has applied for an IDE from the FDA.
Peter C. Block, MD, director of clinical trials, department of cardiology at Emory University Hospital in Atlanta, acknowledges that the U.S. approach to AVR is more cautious than the European approach. “The problem with European data is that follow up has been historically difficult because of patient mobility. The FDA will want longer term results, before it approves this therapy,” he explains. Also, PARTNER is the first randomized, controlled trial to assess percutaneous AVR.
However, the specialty is exploding as it presents a novel way for physicians to treat an ailing—previously untreatable—population. Leon, who is the interventional principal investigator in PARTNER, explains that the field is in a “rapid period of data accumulation,” adding that the Edwards device was featured in approximately 80 peer-reviewed journals in 2009.
One of the reasons for the sudden popularity in percutaneous AVR is due to the positive outcomes. “Even with a conservative estimate, 10 lives per 100 can be saved per year,” says Jeffrey J. Popma, MD, director of innovations in interventional cardiology at Beth Israel Deaconess Medical Center in Boston. “Also, all the data thus far show that there are marked functional improvements in patients undergoing percutaneous AVR. A patient who would typically be consuming hospital services due to recurrent congestive heart failure now has Class I or Class II symptoms, and an improved quality of life.”
In fact, the European registry data show procedural success rates of 98 percent, a cardiac death rate of 9 percent and an overall one-year survival rate of 70 percent, Grube reports.
“Patients currently selected for percutaneous treatment are generally elderly with important associated diseases and have a finite lifespan,” Popma notes. “In contrast, the average 80-year-old without severe aortic stenosis can now expect, on average, another 8.8 years, compared with a near 40 percent one-year