PROTECT AF at 4 Years: LAA Closure Maintains Efficacy Over Warfarin
Adding another layer to the body of evidence, 4-year results from the PROTECT AF trial showing better efficacy for patients with nonvalvular atrial fibrillation (A-fib) using percutaneous left atrial appendage (LAA) closure compared with warfarin were published in the November 19, 2014, issue of the Journal of the American Medical Association.
The data were first presented more than a year ago at the 2013 Heart Rhythm Society Annual Scientific Sessions in Denver, CO. Meanwhile, more than 5 years have passed since the first US FDA advisory panel meeting—which was then followed by 2 more meetings, the last notable for a sense of waning enthusiasm—and the agency has yet to decide whether to approve the Watchman device (Boston Scientific).
For PROTECT AF, Vivek Y. Reddy, MD, of Mount Sinai School of Medicine (New York, NY), and colleagues randomized 707 patients with nonvalvular A-fib and at least 1 additional stroke risk factor (CHADS2 score ≥ 1) to receive Watchman (n = 463; implantation plus concomitant antithrombotic medication followed by warfarin and aspirin [81-325 mg] for 45 days, clopidogrel and aspirin for 6 months, and aspirin thereafter) or warfarin alone (n = 244; target international normalized ratio 2-3). Baseline characteristics, including stroke risk, were well balanced between the 2 groups.
Noninferiority required a posterior probability > 97.5% and superiority required a posterior probability ≥ 95%. The noninferiority margin was set at a rate ratio of 2.0.
At a mean follow-up of 3.8 years, amounting to a total of
2,621 patient-years, Watchman proved both noninferior and superior to warfarin
for the primary efficacy endpoint of stroke, systemic embolism, and
cardiovascular/unexplained death based on intent to treat. The primary safety
endpoint of procedure-related events and major bleeding also was equivalent
between the 2 groups, though Watchman did not offer superior safety (table 1).
Cardiovascular mortality was lower for Watchman than warfarin at 1.0 vs 2.4 events per 100 patient-years (P = .005) as was all-cause mortality at 3.2 vs 4.8 events per 100 patient-years (P = .04). Hemorrhagic stroke also was less likely with Watchman at 0.2 vs 1.1 events per 100 patient-years (P value not reported).
Efficacy was consistent across subgroups related to sex, age, A-fib pattern, CHADS2 score, LAA morphology, and prior warfarin use. Safety events showed a linear evolution over time for warfarin but were mostly periprocedural for Watchman, consisting of pericardial effusion, procedure-related stroke, and device embolization.
Secondary analyses were performed to evaluate only patients who successfully received Watchman, the per-protocol population, and patients completing both warfarin and clopidogrel therapy—in all cases, risk reductions in the efficacy endpoint were approximately 50%. Results for stroke and cardiovascular/unexplained death also were consistent.
“[A]dverse events in patients undergoing device deployment were predominately procedural,” the paper notes. “Taken together, these findings suggest that the benefit of the device strategy cannot simply be attributed to the transient antithrombotic treatment.”
Not a Device But a Strategy
Dr. Reddy and colleagues stress that LAA closure in PROTECT AF “is not just an implant but a therapeutic strategy involving a procedure plus 6 months of anticoagulation or antithrombotic pharmaceutical intervention (or both) to fully protect [patients…. As such, the] study does not address patients with absolute contraindications to warfarin unable to tolerate this initial anticoagulant transition.” They suggest that the effectiveness of Watchman might even be augmented with shorter durations of postimplant anticoagulation by reducing the odds of bleeding.
The advent of novel oral anticoagulants limits the clinical generalizability of the current findings, the researchers point out, cautioning that the results also may not extend to other LAA closure devices.
Reddy VY, Sievert H, Halperin J, et al. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. JAMA. 2014;312:1988-1998.
- Dr. Reddy reports receiving research grant support and consultant fees from Boston Scientific.
- PROTECT AF: 4-Year Results Show Superiority of Watchman Over Warfarin for A-fib
- Time May Be Running Out for Watchman Amid Weak Support From FDA Panel
- PREVAIL Published: Watchman, Warfarin Show Comparable Stroke Protection in A-fib\