Five-Year Data on LAA Closure Using Watchman Device in Patients With Nonvalvular Atrial Fibrillation Presented, Published
November 2, 2017—Five-year results from the PREVAIL trial comparing left atrial appendage (LAA) closure with the Watchman device (Boston Scientific Corporation) to warfarin in patients with nonvalvular atrial fibrillation, as well as a meta-analysis combining the data with the 5-year findings from the PROTECT AF trial, were reported at TCT 2017, the 29th annual Transcatheter Cardiovascular Therapeutics scientific symposium held October 30 to November 2 in Denver, Colorado. The results were also published simultaneously by Vivek Y. Reddy, MD, et al online in the Journal of the American College of Cardiology.
The PREVAIL analysis found that the first composite coprimary endpoint of stroke, systemic embolism (SE), or cardiovascular/unexplained death did not achieve noninferiority, but the second coprimary endpoint of postprocedure ischemic stroke/SE did achieve noninferiority. The meta-analysis combining the PREVAIL and PROTECT AF experiences demonstrated that LAA closure provides stroke prevention comparable with warfarin, with additional reductions in major bleeding, particularly hemorrhagic stroke, and mortality.
As noted in the TCT announcement, data from the PROTECT AF and PREVAIL trials were pooled for a patient-level meta-analysis because of the trials' identical efficacy endpoint definitions and the near-identical eligibility criteria.
The PROTECT AF and PREVAIL trials enrolled 707 and 407 patients, respectively, who were randomized 2:1 to the LAA closure and warfarin arms. In both trials, patients were followed for the protocol-defined maximum period of 5 years, ending in 2013 and 2017, respectively. Baseline patient characteristics were similar in both studies.
For the PREVAIL trial, all endpoints required the inclusion of the PROTECT AF informative prior, resulting in a calculated 18-month rate of the first coprimary endpoint (composite of stroke, SE, or cardiovascular/unexplained death) of 0.066 with LAA closure versus 0.051 for warfarin, yielding a mean 18-month rate ratio of 1.33 (95% credible interval, 0.78 to 2.13). It did not achieve noninferiority (posterior probability for noninferiority = 88.4%). However, the second coprimary endpoint of postprocedure ischemic stroke/SE did achieve noninferiority (posterior probability for noninferiority = 97.5%).
The calculated 18-month rate for the second coprimary efficacy endpoint was 0.0255 in the LAA closure group versus 0.0135 in the warfarin group (rate difference 0.012; 95% credible interval, -0.0036 to 0.0275) At 5 years, the warfarin arm maintained an unexpectedly low ischemic stroke rate (0.73%), as compared with other studies examining such a regimen.
In the meta-analysis of PROTECT AF and PREVAIL with 5-year follow-up, the composite endpoint was similar between groups (hazard ratio [HR], 0.82; P = .27), as were all-stroke/SE (HR, 0.961; P = .87). The ischemic stroke/SE rate was numerically higher with LAA closure, but this difference did not reach statistical significance (HR, 1.71; P = .08). However, differences in hemorrhagic stroke (HR, 0.2; P = .0022), disabling/fatal stroke (HR, 0.45; P = .03), cardiovascular/unexplained death (HR, 0.59; P = .027), all-cause death (HR, 0.73; P = .035), and postprocedure bleeding (HR, 0.48; P = .0003) favored LAA closure. Therefore, the meta-analysis demonstrates comparable efficacy and stroke rates with no significant difference across subgroups, no significant differences in ischemic stroke rates versus warfarin, and significant, superior reductions in disabling strokes, nonprocedural bleeding, and mortality.
In Boston Scientific's announcement, Dr. Reddy, Principal Investigator and Director of Cardiac Arrhythmia Services for The Mount Sinai Hospital and the Mount Sinai Health System, stated, “With complete 5-year follow-up in two randomized clinical trials, left atrial appendage closure with the Watchman device continues to demonstrate statistically significant reductions in death.
“Importantly, the data further prove the Watchman device is a safe and effective therapeutic alternative for stroke prevention in appropriate patients, enabling them to stop taking warfarin,” concluded Dr. Reddy.