ABSTRACT & COMMENTARY
Is Left Atrial Appendage Occlusion with the Watchman Device a Reasonable Alternative to Anticoagulation with Warfarin?
By Edward P. Gerstenfeld, MD
Professor of Medicine, Chief, Cardiac Electrophysiology, University of California, San Francisco
Dr. Gerstenfeld does research for Biosense Webster, Medtronic, and Rhythmia Medical.
Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: The PREVAIL trial. J Am Coll Cardiol 2014;64:1-12.
The goal of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin Therapy (PREVAIL) trial was to assess the safety and efficacy of left atrial appendage (LAA) occlusion for stroke prevention in patients with atrial fibrillation (AF) compared with long-term warfarin therapy. Patients with AF who had a CHADS2 score ≤ 2, or 1 and another “high” risk factor were eligible for enrollment. Patients were randomly assigned (in a 2:1 ratio) to undergo LAA occlusion with the Watchman device and subsequent discontinuation of warfarin 6 months after implantation (n = 269) or receive continued warfarin therapy (control group, n = 138). There were two coprimary endpoints. The first primary endpoint included a composite of stroke, systemic embolism, and death. The second primary endpoint included the occurrence of stroke or systemic embolism > 7 days after randomization. At 18 months, the rate of the first primary efficacy endpoint was 0.064 in the device group vs 0.063 in the control group, and did not achieve the prespecified noninferiority criteria. The rate for the second primary efficacy endpoint was 0.0253 vs 0.0200, achieving noninferiority. Early safety events occurred in 2.2% of the Watchman device arm, satisfying the prespecified safety performance goal. Pericardial effusions requiring surgical repair decreased from 1.6% to 0.4% with the Watchman device compared to the earlier Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation (PROTECT AF) trial (P < 0.03), and need for pericardiocentesis decreased from 2.9% to 1.5% (P = 0.36). The authors concluded that LAA occlusion is a reasonable alternative to warfarin therapy for stroke prevention in patients with non-valvular AF who do not have an absolute contraindication to short-term warfarin therapy.
COMMENTARY
Stroke remains the most feared complication of AF and stroke prevention is one of the primary treatment objectives in AF patients. While it is well known that clots during AF typically form in the LAA, it had been controversial whether surgical or mechanical exclusion of the LAA would prevent strokes and could be an alternative to long-term systemic anticoagulation. The data are in part limited because our surgical colleagues have not yet performed a proper prospective randomized trial of LAA ligation in patients with AF undergoing cardiac surgery. The PLATO device was the first device developed to allow percutaneous “plugging” of the LAA for stroke prevention.1 The Watchman device represents the next generation of devices capable of plugging the LAA via an atrial transseptal route. The device contains a permeable polyester membrane coating that allows endotheliazation after implant to prevent thrombus formation, and contains barbs that prevent device migration. However, whether complete occlusion of the LAA could be achieved with acceptable risk and without more proximal clot formation has been unclear. The initial PROTECT AF2 study demonstrated equivalence to warfarin after the device was implanted; however, a higher than anticipated periprocedural complication rate led the FDA to mandate a second trial. In this current trial (PREVAIL), the complication rate during device implantation (2.2%) was significantly lower than PROTECT AF. The patients enrolled in PREVAIL had a mean age of 74 years and a reasonable stroke risk (mean CHADS2 score = 2.6 ¡À 1). The primary endpoint for noninferiority, a composite of stroke, systemic embolism, and death, unfortunately was not met by the study endpoints. However, this was largely because the event rate in the control warfarin arm was unusually low (0.063%). The second primary endpoint for noninferiority, the occurrence of stroke or systemic embolism > 7 days after randomization, was met.
Are we now ready to offer our patients left atrial appendage occlusion as an alternative to anticoagulation? Based on the PREVAIL data, I would presume that the FDA will eventually approve the Watchman device. However, I think it is a bit premature to pursue this strategy wholeheartedly. Although the complication rate in the PREVAIL study was considered acceptable, the investigators still had special expertise and training in implantation of these devices. Complication rates in the real world will undoubtedly be higher, particularly in the elderly population with AF. In addition, several alternative anticoagulants are now available that are safer than warfarin, including dabigatran, rivaroxaban, and apixaban. Patients treated with apixaban in the ARISTOTLE trial,3 for example, had a lower overall mortality and significantly lower intracranial hemorrhage rate compared to warfarin. Anticoagulants also can be taken once or twice daily without any blood tests. Whether the LAA occlusion devices are truly “noninfeiror” to these new agents has not yet been tested. In addition, several other devices are currently being studied, including the Amplatzer LAA plug and epicardial LARIAT device. How these devices compare with the Watchman device is unknown. Certainly patients at high stroke risk who have bleeding risks that preclude long-term anticoagulation with warfarin should be considered candidates for LAA occlusion. Keep in mind that using the Watchman device, a minimum of 45 days of anticoagulation with warfarin was still required (although a preliminary study has suggested that asprin/clopidogrel treatment may be a suitable alternative).4 In the future, I have no doubt that LAA occlusion will be an option for patients with AF and stroke risk who cannot tolerate long-term anticoagulation. Whether these devices will be considered an “alternative” to systemic pharmacologic anticoagulation remains to be determined.
REFERENCES
- Ostermayer SH, et al. Percutaneous left atrial appendage transcatheter occlusion (PLAATO system) to prevent stroke in high-risk patients with non-rheumatic atrial fibrillation: Results from the international multi-center feasibility trials. J Am Coll Cardiol 2005;46:9-14.
- Holmes DR, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients
with atrial fibrillation: A randomised non-inferiority trial. Lancet 2009;374:534-542.
- Granger CB, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-992.
- Reddy VY, et al. Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: The ASAP study (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology). J Am Coll Cardiol 2013;61:2551-2556.
