Full article reprinted from "The Gray Sheet" - April 06, 2009
Find out how FDA's Circulatory System Devices panel will meet April 23 to review a PMA for Atritech's Watchman minimally invasive stroke-prevention device for patients with atrial fibrillation, according to the company.
Full article reprinted from "The Gray Sheet" - April 06, 2009
The private Plymouth, Minn., company says it will be able to complete the FDA review process thanks to the $30 million in financing it recently secured from five venture capital groups. The company has raised about $75 million over the last three years.
The company has already secured a CE mark for Watchman and says part of the latest financing will go toward commercializing the device in Europe.
The panel meeting marks a critical milestone for the company, which was founded in 2000 to develop the stroke-prevention technology invented by two cardiologists at the Minneapolis Heart Institute, Robert Hauser and Robert Van Tassel. Intellectual property bought from Ev3 in 2007 for about $15.6 million also contributed to Watchman.
Atritech Adapts Surgical Procedure To Catheter
Atritech's PMA, submitted in August, is supported by results from the PROTECT AF trial, which were first reported March 28 at the American College of Cardiology (ACC) Annual Scientific Sessions in Orlando, Fla., by principal investigator David Holmes, M.D., Mayo Clinic, Rochester, Minn.
Holmes explained that atrial fibrillation (AF) prevents the upper chambers of the heart from pumping efficiently, allowing blood to pool and clot in the atrium, creating emboli in the bloodstream that can cause stroke. Stroke is the leading cause of disability and the third most common cause of death in patients with AF.
According to Holmes, about 87% of strokes are caused by thromboemboli and over 90% of thrombus accumulation begins in the left atrial appendage, a pouch that opens off the left side of the main atrial cavity, overlapping the root of the pulmonary artery.
To prevent clotting, patients with AF are usually prescribed the anti-coagulant drug warfarin, which carries the risk of serious bleeding complications. For example, according to a 2006 study Holmes cited, for every 1,000 patient-years, warfarin therapy in AF patients prevents about 28 strokes but causes 11 fatal bleeds.
Watchman is a polyester-covered nitinol cage that is expanded to block the opening between the left atrial appendage and the rest of the atrium. Fixation barbs on the perimeter of the cage keep it in place.
Surgical techniques to close the left atrial appendage in AF patients have been performed for years, but the procedure is very invasive. Watchman is delivered percutaneously by a catheter pushed through the femoral vein and across the septum.
Trial Proves Efficacy, Raises Safety Issues
PROTECT AF randomized 707 patients at 59 centers in the United States and Europe to treatment with Watchman or long-term warfarin therapy. The primary endpoint of the study was a composite of reduction in strokes and cardiovascular deaths.
Patients in Watchman group continued to take warfarin for 45 days after the implant procedure, at which time they stopped taking it if their doctor determined that the flow from the left atrial appendage was sufficiently occluded.
The device was successfully implanted in about 91% of the patients in which it was attempted, and 87% of patients who were successfully implanted with the device stopped taking warfarin at the 45-day check-up. By two years post procedure, 94% were able to stop taking the drug. Overall, 86% of patients randomized into the Watchman group were both successfully implanted and eventually able to stop taking warfarin altogether because the device had sufficiently lowered their risk of stroke, Holmes reported.
After 900 patient-years, the stroke and cardiovascular death rate for the Watchman group was 3.4 per 100 patient-years versus 5.0 per 100 patient-years in the warfarin group. This 32% risk reduction shows Watchman is non-inferior to long-term warfarin therapy for the primary endpoint. Watchman patients experienced a 50% overall reduction in stroke, death and adverse events compared to their warfarin-group counterparts.
Holmes also pointed out that the trial showed Watchman to be statistically non-inferior to long-term warfarin therapy when stroke and death rates were analyzed separately. In addition, the rate of hemorrhagic stroke was 91% lower in the device group, a statistically superior result.
Six control patients, including four who died, suffered a hemorrhagic stroke, while the only hemorrhagic stroke in the Watchman group happened 15 days after the implant while the patient was still on warfarin.
However, Watchman recipients suffered more procedure-related complications than the warfarin group - 8.7 per 100 patient-years versus 4.2 per 100 patient years.
Most of the Watchman-group complications were related to the implant procedure, Holmes noted. Pericardial effusion, or accumulation of fluid in the pericardial space, was the most common adverse event in the Watchman group; stroke and bleeding were the most common adverse events in the warfarin group.
Holmes reported that PROTECT AF researchers have made procedural modifications and training enhancements throughout the trial that are expected to decrease procedure-related adverse events. Among the 88 patients treated with Watchman under a continued access protocol after the trial ended, there has been only one pericardial effusion.
So far, the longest any patient has had Watchman is about four years, according to the company, which plans to follow all of the trial patients for five years.
Because PROTECT AF randomized patients to Watchman or long-term warfarin therapy, patients who cannot take warfarin due to an especially high risk of bleeding were not eligible for the trial and therefore are not included in the indication Atritech is requesting from FDA.
Co-principal investigator Horst Sievert, University of Frankfurt, Germany, predicted at the ACC conference that if the device gets FDA approval, most doctors will be cautious at first, initially only implanting it in AF patients who cannot take warfarin and therefore have no other option for preventing stroke.
"Only later, after we see how well this really works, will we place the device in patients who can take warfarin," he said.
- Reed Miller
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