Will Obliteration of the Left Atrial Appendage Obliterate the Need for Warfarin? Results of PROTECT-AF Presented at the ACC

Dear Readers, Prevention of stroke is one of the cornerstones of therapy for patients with atrial fibrillation (AF). The most effective drug to prevent thromboembolism in patients with AF and risk factors for stroke is warfarin (Coumadin). The ACTIVE-W trial showed us that a combination of clopidogrel (Plavix) and aspirin cannot substitute for warfarin. However, as most health care providers and patients are well aware, there are major limitations to the use of warfarin — a significant risk of bleeding, a narrow therapeutic window, frequent food and drug interactions, and a need for frequent blood draws to guide dosing. Fortunately, there are numerous drugs under development that might replace warfarin, including direct thrombin and factor Xa inhibitors, and oral forms of heparin. Until then, our only drug option is warfarin. Furthermore, even if a substitute for warfarin becomes available, we will still have to contend with bleeding complications. Because the left atrial appendage (LAA) is the most common location for clots to form in patients with AF, it is logical that obliteration of the LAA could reduce the risk of stroke in these patients. Although the LAA can be oversewn surgically, there is a strong interest in a safe method to occlude the LAA percutaneously. The company Atritech, Inc. has developed a self-expanding, fabric-covered, cage-like device that can be placed transseptally using a catheter delivery system to occlude the LAA. This device, called the Watchman® (Atritech, Inc., Plymouth, MN), has been tested in the Embolic Protection in Patients with Atrial Fibrillation (PROTECT-AF) trial. A picture of the Watchman® device (Figure 1) and a transesophageal echocardiographic image (Figure 2) are shown after the device was deployed in a patient at our institution as part of the PROTECT-AF trial. The results of the trial were presented during the Late Breaking Clinical Trials session of the i2 Summit during the recent American College of Cardiology meeting in Orlando. The PROTECT-AF study randomized 707 patients with AF and an indication for warfarin to implantation of the device versus long-term warfarin therapy in a 2:1 ratio. Patients who underwent implantation of the device were required to continue their warfarin until there was evidence by transesophageal echocardiography 45 days later that the LAA was completely occluded. In the trial, 87% of patients were able to stop warfarin at 45 days and were prescribed clopidogrel for six months after the warfarin was stopped. The study found that the device was no worse than (noninferior to) warfarin. The combined rate of all strokes and cardiovascular death was 3.4% in patients who received the device compared to 5.0% in patients in the anticoagulation arm. The rate of hemorrhagic stroke in the device patients was significantly lower than in the warfarin patients. This is an encouraging study, but there are many unanswered questions. For example: • There was a 5% risk of a pericardial effusion with the device. Will the complication rate be lower in the real world with availability of the second-generation device that was introduced during the trial and as lessons are learned, or will the complication rate be higher in the real world as operators with less experience begin implanting the devices? • Who should be implanting the devices? Interventional cardiologists who have experience delivering similar devices, or electrophysiologists who are familiar with the left atrial appendage? • The study only allowed patients to be enrolled who could tolerate warfarin and required that patients who underwent device implantation stay on warfarin for at least 45 days postoperatively. How many patients will be candidates for the device? • Will the perception that an alternative to warfarin will soon be commercially available limit the number of patients referred for device implantation? • Will patients with recurrent persistent AF need to undergo a TEE or receive warfarin before cardioversion? Warfarin was first registered for use to kill rodents in 1948 and approved for use in humans as an anticoagulatant in the early 1950s. It has taken quite some time to see an alternative on the horizon. We will watch closely as the Watchman® device is the subject of an FDA advisory panel on April 23, 2009. Sincerely, Bradley P. Knight, MD, FACC, FHRS Editor-in-Chief, EP Lab Digest