Pam Alexson
04-24-2009, 09:02 AM
Who's watching the Watchman? FDA advisory panel reviews LAA closure device tomorrow
APRIL 22, 2009 | Michael O'Riordan
Gaithersburg, MD - A novel device for closure of the left atrial appendage (LAA) that provides an alternative to warfarin therapy for the prevention of stroke in patients with atrial fibrillation (AF) will get its hearing before a Food and Drug Administration advisory panel Thursday morning.
The Circulatory Systems Devices Panel will discuss, evaluate, and vote on a premarket approval application for the Watchman (Atritech, Plymouth, MN), a device placed distally to the ostium of the LAA to occlude flow and prevent the migration of thrombus forming in the appendage.
During the daylong event, the advisory panel will hear evidence from the FDA and the device sponsor. In documents released in advance of the panel, the FDA points to "several confounding issues" it wants the panel to consider when assessing the results of the Embolic Protection in Patients with Atrial Fibrillation (PROTECT-AF) trial, the pivotal premarket approval study. Among them is patient selection, since the trial excluded patients at higher risk of poor outcomes, including those with advanced heart failure, recent stroke or MI, and carotid disease. There are also some concerns about the long-term durability of the device. The FDA researchers note there are effectiveness data beyond two years in just 22% of implanted patients.
As previously reported by heartwire—results of the PROTECT-AF study were presented last month at the American College of Cardiology 2009 Scientific Sessions—among AF patients who were candidates for warfarin therapy, device closure of the LAA using the Watchman device was associated with a reduction in hemorrhagic stroke risk vs warfarin, and all-cause-stroke and all-cause-mortality outcomes were noninferior to warfarin.
Study investigators, led by Dr David Holmes (Mayo Clinic, Rochester, MN), noted that safety events, particularly pericardial effusion, were more common in the device group, but these decreased over time with procedural modifications and enhanced training. Overall, 87% of patients receiving the device were able to stop taking warfarin.
However, several of the issues the FDA raises in its briefing document to the advisory panel are related to warfarin therapy. In the intention-to-treat (ITT) analysis, the agency notes that some patients continued taking warfarin even after receiving the device, while some patients in the warfarin arm stopped medical therapy, and this makes interpretation of the ITT analysis difficult.
Another issue the FDA wants the panel to consider is the primary end point, a composite that includes all strokes, ischemic and hemorrhagic; cardiovascular or unexplained death; and systemic embolization. It suggests that these end points be examined individually and in the context of concomitant medications. Also, it draws attention to the formation of thrombus on the device in 3.8% of patients, including one patient who had a cerebral ischemic event.
In its briefing document, the FDA said that, if approved, longer-term safety data are needed, as well as better clarification about the patient's ability to discontinue warfarin. It notes that the PROTECT-AF trial was conducted at centers with experience in clinical trials and with investigational devices, so the generalizability of the findings is a concern, as is the impact of the learning curve on overall patient safety.
Dr William Maisel (Beth Israel Deaconess Medical Center, Boston, MA) is scheduled to chair tomorrow's advisory panel.
Atritech funded the PROTECT-AF study.
Related links
ACC 2009: From the eye of the storm in Orlando
[Sections > Editorial series; Apr 02, 2009]
PROTECT-AF: Device closure of LAA may provide alternative to warfarin to prevent stroke in AF
[Brain/Kidney/Peripheral > Brain/Kidney/Peripheral; Mar 28, 2009]
APRIL 22, 2009 | Michael O'Riordan
Gaithersburg, MD - A novel device for closure of the left atrial appendage (LAA) that provides an alternative to warfarin therapy for the prevention of stroke in patients with atrial fibrillation (AF) will get its hearing before a Food and Drug Administration advisory panel Thursday morning.
The Circulatory Systems Devices Panel will discuss, evaluate, and vote on a premarket approval application for the Watchman (Atritech, Plymouth, MN), a device placed distally to the ostium of the LAA to occlude flow and prevent the migration of thrombus forming in the appendage.
During the daylong event, the advisory panel will hear evidence from the FDA and the device sponsor. In documents released in advance of the panel, the FDA points to "several confounding issues" it wants the panel to consider when assessing the results of the Embolic Protection in Patients with Atrial Fibrillation (PROTECT-AF) trial, the pivotal premarket approval study. Among them is patient selection, since the trial excluded patients at higher risk of poor outcomes, including those with advanced heart failure, recent stroke or MI, and carotid disease. There are also some concerns about the long-term durability of the device. The FDA researchers note there are effectiveness data beyond two years in just 22% of implanted patients.
As previously reported by heartwire—results of the PROTECT-AF study were presented last month at the American College of Cardiology 2009 Scientific Sessions—among AF patients who were candidates for warfarin therapy, device closure of the LAA using the Watchman device was associated with a reduction in hemorrhagic stroke risk vs warfarin, and all-cause-stroke and all-cause-mortality outcomes were noninferior to warfarin.
Study investigators, led by Dr David Holmes (Mayo Clinic, Rochester, MN), noted that safety events, particularly pericardial effusion, were more common in the device group, but these decreased over time with procedural modifications and enhanced training. Overall, 87% of patients receiving the device were able to stop taking warfarin.
However, several of the issues the FDA raises in its briefing document to the advisory panel are related to warfarin therapy. In the intention-to-treat (ITT) analysis, the agency notes that some patients continued taking warfarin even after receiving the device, while some patients in the warfarin arm stopped medical therapy, and this makes interpretation of the ITT analysis difficult.
Another issue the FDA wants the panel to consider is the primary end point, a composite that includes all strokes, ischemic and hemorrhagic; cardiovascular or unexplained death; and systemic embolization. It suggests that these end points be examined individually and in the context of concomitant medications. Also, it draws attention to the formation of thrombus on the device in 3.8% of patients, including one patient who had a cerebral ischemic event.
In its briefing document, the FDA said that, if approved, longer-term safety data are needed, as well as better clarification about the patient's ability to discontinue warfarin. It notes that the PROTECT-AF trial was conducted at centers with experience in clinical trials and with investigational devices, so the generalizability of the findings is a concern, as is the impact of the learning curve on overall patient safety.
Dr William Maisel (Beth Israel Deaconess Medical Center, Boston, MA) is scheduled to chair tomorrow's advisory panel.
Atritech funded the PROTECT-AF study.
Related links
ACC 2009: From the eye of the storm in Orlando
[Sections > Editorial series; Apr 02, 2009]
PROTECT-AF: Device closure of LAA may provide alternative to warfarin to prevent stroke in AF
[Brain/Kidney/Peripheral > Brain/Kidney/Peripheral; Mar 28, 2009]