It’s easy to understand the excitement about the PARTNER trial, sponsored by Edwards Lifesciences (Irvine, California), the company that makes the much talked about transcatheter aortic valve replacement (TAVR) device, called the Sapien. After all, given the choice between open heart surgery or a non-surgical alternative most patients would prefer the latter. However, the data from the study, which was presented earlier this week at the American College of Cardiology (Washington) annual meeting in New Orleans, showed that TAVR patients were also more likely to have a stroke following the procedure.
In the study, major strokes were higher for TAVR at both 30 days (3.8% vs. 2.1%) and one year (5.1% vs. 2.4%). At 30 days major vascular complications also were much more common after TAVR (11% vs. 3.2%), but the TAVR group’s rates were much lower for major bleeding (9.3% vs. 19.5%) and new-onset irregular heart rhythms of atrial fibrillation (8.6% vs. 16%).
Matthew Reynolds, MD, director of economics and quality of life research at Harvard Clinical Research Institute and a cardiologist for the VA Boston Healthcare System who presented the study results, noted that the patient population in the clinical trial was unusually old and sick for a clinical trial. “The mean age was 83, there was a very high prevalence of coronary artery disease and previous bypass surgery and about one-quarter had advanced lung disease. Despite this, the patients treated with TAVR did remarkably well.”
When asked how many patients will be affected by TAVR once it is FDA approved, Smith said “thousands” initially, and soon “tens of thousands,” but that it would probably be several years before the impact reaches hundreds of thousands.
Still, while Smith said that the results clearly show that TAVR is an excellent alternative to surgical AVR in high-risk patients, he noted that recommendations to individual patients “will need to weigh the appeal of avoiding open-heart surgery, with its known risks, against less invasive TAVR with different and less well understood risks, as well as the absence of long-term follow-up. He also noted that “future trials will help delineate the role of TAVR in intermediate risk patients.”
The pressure to put the Sapien into intermediate risk patients will be overwhelming, and not just from patients needing the procedure. Larry Biegelsen a med-tech research analyst with Wells Fargo Securities, wrote in a note that once the Sapien, and a comparable device developed by Medtronic (Minneapolis) called the Corevalve, are cleared for sale in the U.S., they could generate sales of $2.4 billion and account for more than one in three aortic valve repairs by 2015. Numbers like that will certainly remind investors and doctors of the halcyon days of the drug-eluting stent craze of the early 2000s.
The genie may already be out of the bottle. Already researchers are talking to officials at the FDA and other regulatory agencies worldwide about including less risky patients in future studies. The procedure is now used in people who have about a 10% risk of dying in the hospital, and there are plans to lower that to a 4% risk in the U.S. and 3% in Europe.
Still, the results should improve with time because the study used Edwards’s first-generation device and 19 of the 26 centers had no prior experience with it. And when the only other alternative is open-heart surgery, many people will leap at the chance to have the procedure, even though open-heart surgery has proven to be extraordinarily effective, with death rates of less than 1% and the valves implanted via the procedure lasting for a quarter century.
Ralph Brindis, MD, president of ACC, and an interventional cardiologist at Kaiser Permanente (Oakland, California), agreed that the technology has great promise but also cautioned his colleagues in the field regarding dissemination of the new technology in order to ensure safety and efficacy for patients.
“This is a truly game-changing clinical trial. There are a huge amount of patients that are not getting therapy. It will take a while to ramp up experience in the centers, and we as a profession have to be responsible,” Brindis said. “This is a landmark technology but not everyone should be doing this. How can we as a society responsibly put together proper programs of diffusion of these new technologies?”