Percutaneous Closure of Left Atrial Appendage vs Warfarin Therapy
Abstract & Commentary
By Harold L. Karpman, MD, FACC, FACP, Clinical Professor of Medicine, UCLA School of Medicine. Dr. Karpman reports no financial relationship to this field of study.
Synopsis: The efficacy of percutaneous closure of the LAA with the WATCHMAN® left atrial closure device was found to be non-inferior to that of standard warfarin therapy for prevention of stroke, cardiovascular death, and/or systemic embolism and, therefore, the device might provide an alternative strategy to chronic warfarin therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation.
Source: Reddy VY, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: A randomized non-inferiority trial. Lancet 2009;374:534-542.
Atrial fibrillation is the most common sustained cardiac arrhythmia and it is currently affecting an estimated 6 million individuals in the United States.1 Because it occurs mainly in the elderly, its prevalence is expected to increase in parallel with the increasing age of the population and has been predicted to climb to 15.9 million Americans by 2050.2,3 Atrial fibrillation occurs in one in four persons older than age 40,4 and stroke, which is its most serious complication, occurs in 5% of non-anticoagulated patients every year. Stroke is the third most frequent cause of death in the United States and the leading cause of serious disability. It occurs with increasing frequency with increasing age (i.e., 23.5% of those ages 80-89 years) in patients afflicted with atrial fibrillation;4,5 therefore, stroke prophylaxis is a crucial component of management of this arrhythmia.
Randomized controlled trials have demonstrated that warfarin is effective in preventing stroke, more so than aspirin or combination aspirin-clopidogrel;6,7 however, warfarin is often not tolerated well and, because of its very narrow therapeutic range, its use carries a high risk for bleeding complications.8 Also, only about 50% of patients who are eligible for long-term warfarin therapy actually receive well-controlled warfarin dosing that achieves what is universally considered to be the appropriate therapeutic result.9 Although pharmacological alternatives to warfarin are being investigated and several of these new anticoagulants seem promising,10 other forms of therapy (such as anatomic closure of the left atrial appendage [LAA], which is the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation11), have demonstrated exceptionally good risk-to-benefit ratios in pilot studies.12-15
Reddy and colleagues performed a non-masked, multicenter, randomized, non-inferiority trial to determine the efficacy and safety of the WATCHMAN LAA closure device in patients with paroxysmal, persistent, or permanent non-valvular atrial fibrillation. A total of 707 eligible patients were randomly assigned either to percutaneous closure of the LAA and subsequent discontinuation of warfarin or to warfarin treatment. Efficacy was assessed by evaluating the primary composite endpoints of stroke, cardiovascular death, and/or systemic embolism. The authors determined that although there was a higher rate of adverse safety events in the intervention group, consisting mainly of peri-procedural complications, the efficacy of percutaneous closure of the LAA with this device was not inferior to that of warfarin therapy. The authors concluded that closure of the LAA might provide an acceptable alternative strategy to chronic warfarin therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation.
Despite its limitations, at this time warfarin therapy is still the treatment of choice for patients with non-valvular atrial fibrillation who are both suitable and who have clear indications for long-term oral anticoagulation. However, it must be clearly recognized that even in the Reddy trial, therapeutic INR values were achieved in only 66% of the patients despite close INR follow-up. The most common primary safety complications in patients assigned to warfarin were major bleeding and hemorrhagic stroke, which occurred throughout the follow-up period. By contrast, there was a 90% reduction in the rate of hemorrhagic stroke in patients who received the WATCHMAN device, although peri-procedural complications were somewhat more frequent but usually these complications did not lead to long-term sequelae. Most patients who were treated with the LAA closure device were able to discontinue warfarin 6 months after device implantation without developing an increased risk of subsequent stroke.
Because of the therapeutic difficulties associated with long-term warfarin therapy, cardiologists are eagerly awaiting data from ongoing trials of the newer generations of direct thrombin inhibitors being used in the population of patients with non-valvular atrial fibrillation. However, larger, adequately powered studies that compare medical therapy with percutaneous closure of the LAA by percutaneous device deployment should certainly be performed, especially in high-risk patients and in those with a previous transient ischemic attack or an ischemic stroke, to determine exactly where this mechanical device might fit into our therapeutic armamentarium even if the direct thrombin inhibitors become available. At the present time, because at least one-third of patients receiving warfarin therapy are not achieving therapeutic goals, LAA closure with device therapy may appropriately become more widespread in certain patient groups, especially if the direct thrombin inhibitors prove to be ineffectual or are delayed significantly in their release to the general public.
1. Miyasaka Y, et al. Secular trends in the incidence of atrial fibrillation in Olmstead County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006;114:119-125.
2. Stewart S, et al. Population prevalence, incidence, and predictors of atrial fibrillation in the Renfrew/Paisley study. Heart 2001;86:516-521.
3. Ruigomez A, et al. Incidence of chronic atrial fibrillation in general practice and its treatment pattern. J Clin Epidemiol 2002;55:358-363.
4. Lloyd-Jones DM, et al. Lifetime risk for development of atrial fibrillation: The Framingham Heart Study. Circulation 2004;110:1042-1046.
5. Lin HJ, et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke 1996;27:1760-1764.
6. Hart RG, et al. Meta-analysis: Antithrombotic therapy to prevent stroke in patients who had nonvalvular atrial fibrillation. Ann Intern Med 2007;146:857-867.
7. Go AS, et al. Anticoagulation therapy for stroke pre- vention in atrial fibrillation: How well do randomized trials translate into clinical practice? JAMA 2003; 290:2685-2692.
8. Gage BF, et al. Adverse outcomes and predictors of underuse of antithrombotic therapy in medicare beneficiaries with chronic atrial fibrillation. Stroke 2000;31: 822-827.
9. Walker AM, Bennett D. Epidemiology and outcomes in patients with atrial fibrillation in the United States. Heart Rhythm 2008;5:1365-1372.
10. Haas S. New anticoagulants toward the development of an "ideal" anticoagulant. Vasa 2009;38:13-29.
11. Ostermayer SH, et al. Percutaneous left atrial appendage transcatheter occlusion (PLAATO system) to prevent stroke in high-risk patients with non-rheumatic atrial fibrillation. J Am Coll Cardiol 2005;46:9-14.
12. Sievert H, et al. Percutaneous left atrial appendage transcatheter occlusion to prevent stroke in high-risk patients with atrial fibrillation early clinical experience. Circulation 2002;105:1887-1889.
13. Hanna IR, et al. Left atrial structure and function after percutaneous left atrial appendage transcatheter occlusion (PLAATO): Six month echocardiographic follow-up. J Am Coll Cardiol 2004;43:1868-1872.
14. Fountain RB, et al. The PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) trial. Am Heart J 2006;151:956-961.
15. Sick PB, et al. Initial worldwide experience with the WATCHMAN left atrial appendage system for stroke prevention in atrial fibrillation. J Am Coll Cardiol 2007;49:1490-1495.