Prospective Randomized Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin Therapy
Key result
Watchman LAAO fails to achieve noninferiority to warfarin for stroke, systemic embolism, and cardiovascular death.
- rate ratio 1.07
- 95% CI 0.57 to 1.89
- n=407
Why the study?
In PROTECT AF, LAA occlusion was noninferior to warfarin for stroke prevention in nonvalvular AF, but a periprocedural safety hazard was identified.
Does left atrial appendage occlusion with the Watchman device reduce stroke, systemic embolism, and cardiovascular/unexplained death in patients with nonvalvular atrial fibrillation compared to long-term warfarin therapy?
Key Points
- To assess the safety and efficacy of left atrial appendage occlusion using the Watchman device compared with chronic warfarin therapy for stroke prevention in patients with nonvalvular atrial fibrillation.
- Prospective, randomized clinical trial enrolling patients with nonvalvular atrial fibrillation and a CHADS2 score ≥2 (or 1 with an additional risk factor).
- Participants were randomly assigned in a 2:1 ratio to receive Watchman device implantation with subsequent warfarin cessation (n = 269) or continuous warfarin therapy (n = 138) with an 18-month follow-up.
- The first coprimary composite endpoint of stroke, systemic embolism, and cardiovascular/unexplained death at 18 months was 0.064 in the device arm versus 0.063 in the control arm (rate ratio 1.07, 95% CrI: 0.57 to 1.89), which did not achieve prespecified noninferiority (upper boundary criteria ≥1.75).
- The second coprimary efficacy endpoint of stroke or systemic embolism >7 days postrandomization was 0.0253 for the device group versus 0.0200 for controls (risk difference 0.0053, 95% CrI: -0.0190 to 0.0273), successfully demonstrating noninferiority.
- Early safety events occurred in 2.2% of device patients, and overall procedural adverse events were significantly lower than in the prior PROTECT AF trial (4.2% vs. 8.7%; p = 0.004), including fewer pericardial effusions requiring surgical repair (0.4% vs. 1.6%; p = 0.027).
Study Design
Type
RCT (n=407)
Randomization
2:1 ratio
Structured PICO
Does left atrial appendage occlusion with the Watchman device reduce stroke, systemic embolism, and cardiovascular/unexplained death in patients with nonvalvular atrial fibrillation compared to long-term warfarin therapy?
P
Population
407 patients with nonvalvular atrial fibrillation and a CHADS2 score ≥2 or 1 plus another risk factor, followed for 18 months.
I
Intervention
Left atrial appendage (LAA) occlusion (Watchman device) and subsequent discontinuation of warfarin
C
Comparator
Chronic long-term warfarin therapy
O
Outcome
Two efficacy coprimary endpoints: 1) composite of stroke, systemic embolism [SE], and cardiovascular/unexplained death at 18 months; 2) stroke or SE >7 days postrandomization. One safety coprimary endpoint (early safety events).composite
Main Result
Relative Risk: 1.07 (95% CI 0.57–1.89)
Absolute Event Rate: 0.064% vs 0.063%
Authors
Discussion
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
SESteven E. NissenCardiologist, Cleveland Clinic Foundation
“The study is not big enough to confirm efficacy. It's extremely difficult to see how this device could be approved by the FDA under the circumstances as we currently understand them.”
“Taken in totality, the Watchman studies are the first to demonstrate, in a prospective randomized fashion, the utility of exclusion of the LAA in preventing stroke in patients with [nonvalvular A-fib] compared with warfarin.”
“These data have shown preliminary results for all 407 enrolled PREVAIL patients, as well as the PROTECT AF patients included as a part of the Bayesian analysis. The follow-up is still ongoing and final validation is not yet complete.”
Implication
LAA occlusion with the Watchman device provides a reasonable alternative to warfarin for stroke prevention in nonvalvular atrial fibrillation, demonstrating improved procedural safety compared to prior trials.
Cite This Study
Holmes et al. (2014) conducted an RCT in nonvalvular atrial fibrillation (n=407). Watchman Left Atrial Appendage Closure Device vs. chronic warfarin therapy was evaluated on composite of stroke, systemic embolism, and cardiovascular/unexplained death (rate ratio 1.07, 95% CI 0.57 to 1.89). Left atrial appendage occlusion using the Watchman device did not achieve noninferiority to warfarin for stroke, systemic embolism, and cardiovascular death (rate ratio 1.07; 95% CrI 0.57-1.89).