The long-term results of the PROTECT AF trial have confirmed initial findings that showed that closure of the left atrial appendage (LAA) with the Watchman device (Boston Scientific / Atritech) is non-inferior to warfarin therapy in stroke prevention, systemic embolism and cardiovascular death of atrial fibrillation patients. However, adverse safety periprocedurial events seem to be more common with the Watchman device.
Vivek Y Reddy, Mount Sinai School of Medicine, New York, USA, and others recently reported the updated results ahead of print in Circulation.
The PROTECT AF study was a prospective, unblinded, randomised, multicentre trial conducted in the USA and Europe to determine the efficiency and safety of percutaneous closure of the left atrial appendage compared with long-term warfarin therapy in patients with non-valvular atrial fibrillation at risk for stroke.
The results, published in The Lancet in 2009 (Holmes et al; 374, No. 9689, 534-542), were based on the monitoring of 1,050 patient-years, which showed no inferiority in patients undergoing left atrial appendage closure (efficacy event rate 3.0%) compared to patients treated with warfarin therapy (efficacy event rate 4.9%) in terms of preventing stroke, systemic embolism and cardiovascular death. However, serious safety events were more frequent in the device group (7.4 events per 100 patient-years) compared with the warfarin group (4.4 events per 100 patient-years). The majority of these safety events were linked to the procedural implant.
Reddy et al noted: “While the initial results validated the hypothesis that the left atrial appendage is the principal source of thromboembolism in patients with non-valvular atrial fibrillation, several factors limited interpretation and generalisability. Relatively few patients had been followed for two or more than two years, raising questions about efficacy over time.” Therefore, in the current analysis, Reddy et al set out to evaluate the long-term efficacy of left atrial appendage closure in 1,588 patient-years (median follow-up 2.3±1.1 years).
In this study, the authors randomised 707 patients with non-valvular atrial fibrillation and at least one risk factor (age >75, hypertension, heart failure, diabetes or previous stroke) to either the device (463 patients) or continued warfarin (244 patients) in a 2:1 ratio. Warfarin was also continued in the device group for 45 days, followed by clopidogrel for four and a half months and lifelong aspirin. Four hundred and sixty nine patients completed two years of follow-up (319 in the device group and 150 in the warfarin group). An analysis of treatment efficacy in 18% of patients with prior thromboembolism and with the highest risk for stroke was also undertaken.
The composite primary efficacy event was 3.0% per 100-patient years in the device group and 4.3% per 100-patient years in the warfarin group (probability of non-inferiority >0.999). This demonstrates, according to the authors, that the Watchman device is non-inferior to warfarin in stroke prevention, systemic embolism and cardiovascular or unexplained death of atrial fibrillation patients.
With regards to safety, the primary adverse outcome rate was higher in the left atrial appendage closure group (5.5%) that in the control group (3.6%) with most events occurring early. The authors noted: “Over time, adverse events continued to accrue in the control group, while the majority of events in the device group occurred proximate to the implantation procedure, particularly pericardial tamponade and procedure-related stroke presumably air or thrombus embolism related to catheter manipulation.” Reddy et al commented that “While operator experience can certainly minimise the rate of these events, it will likely be further improvements in device design that will ultimately serve to minimise these complications to a minimal level.”
Moreover, observations in the group treated for secondary stroke prevention favoured the Watchman device over the warfarin group alone with annual stroke rates of 5.3% and 8.2% respectively.
The authors concluded: “Long-term follow-up from PROTECT AF supports the idea that percutaneous left atrial appendage closure with the Watchman device rivals warfarin alone preventing stroke in atrial fibrillation patients.”