Percutaneous Closure of Left Atrial Appendage May Decrease the Risk of Death and Hemorrhagic Stroke Compared to Warfarin in Patients with Nonvalvular Atrial Fibrillation
EBM Focus - Volume 9, Issue 47
Atrial fibrillation affects 1.5-2% of the general population and is associated with a five-fold increased risk of stroke (Eur Heart J 2012 Nov;33(21):2719). Antithrombotic therapy is consistently recommended for most patients with atrial fibrillation and until recently warfarin, a vitamin K antagonist, has been the antithrombotic of choice (J Am Coll Cardiol 2014 Mar 28 early online, Eur Heart J 2010 Oct;31(19):2369, Can J Cardiol 2012 Mar-Apr;28(2):125). Warfarin use requires monthly blood monitoring and is associated with an increased risk of bleeding. The left atrial appendage has been suggested as a major source of thromboembolism in patients with atrial fibrillation and left atrial appendage closure without long-term antithrombotic therapy may prevent stroke (Circulation 2002 Apr 23;105(16):1887). The PROTECT AF trial compared percutaneous device closure of left atrial appendage vs. warfarin in 707 patients with nonvalvular atrial fibrillation plus ≥ 1 risk factor for stroke including age ≥ 75 years, history of previous stroke or transient ischemic attack, hypertension, diabetes, heart failure, or left ventricular systolic dysfunction (Lancet 2009 Aug 15;374(9689):534). A four year follow-up of the PROTECT AF trial was recently published, providing long term efficacy and safety data.
In the PROTECT AF trial, patients randomized to left atrial appendage closure initially continued taking warfarin and aspirin to promote device endothelialization. At 45 days after the procedure, 86.8% of patients receiving device closure were able to discontinue warfarin and 93.2% discontinued warfarin within 1 year. After randomization, 8.2% of patient did not receive the intervention to which they were randomized and 15% of patients withdrew or were lost to follow-up before the 4 year evaluation, but all patients were included in analysis. Comparing device closure vs. warfarin over a mean follow-up duration of 3.8 years (2,621 patient-years), device closure was associated with a decreased risk of hemorrhagic stroke (0.2 per 100 patient-years vs. 1.1 per 100 patient-years, p < 0.05), cardiovascular or unexplained death (1 per 100 patient-years vs. 2.4 per 100 patient-years, p < 0.05), and all cause mortality (3.2 per 100 patient-years vs. 4.4 per 100 patient-years, p = 0.04). No significant differences were observed in rate of any stroke, ischemic stroke, or adverse events.
The results of this trial suggest that left atrial appendage device closure appears as effective as anticoagulation with warfarin for preventing ischemic stroke and may improve both cardiovascular and overall mortality while reducing the risk of hemorrhagic stroke. The initial trial report found that device closure had more adverse events than warfarin, but most adverse events related to device closure occurred in the periprocedural period, while adverse events associated with warfarin occurred throughout the follow-up period. Therefore, over 4 years of follow-up, the rate of adverse events evened out between the two interventions. Device closure may be especially appealing for patients with increased bleeding risk and patients unable or unwilling to follow the monthly monitoring routine required with warfarin use. However, the results of this trial cannot be extended to novel Factor II and Xa inhibitors and further studies are required to determine the efficacy of percutaneous left atrial appendage closure compared to these newer drug therapies.