PREVAIL: LAA closure reduces stroke risk in nonvalvular AF

Patients with nonvalvular AF who underwent left atrial appendage closure with a self-expanding device had a decreased risk for stroke, major bleeding and mortality compared with those who were treated with warfarin, according to data and a meta-analysis presented at TCT 2017.

“By minimizing major bleeding, particularly hemorrhagic stroke, left atrial appendage (LAA) closure results in less disability or death compared to warfarin,” Saibal Kar, MD, director of interventional cardiac research at the Cedars-Sinai Heart Institute, said during a press conference.

Researchers analyzed 5-year data from the PREVAIL trial, and a meta-analysis was performed using that data with 5-year outcomes from the PROTECT AF trial. Patients from the PREVAIL (n = 407) and PROTECT AF (n = 707) trials were assigned LAA closure with a device (Watchman, Boston Scientific) or warfarin in a two-to-one fashion. Follow-up was conducted for 5 years.

The first primary efficacy endpoint in the PREVAIL trial was a comparison of rate ratios of 18-month event rates for a composite of systemic embolization, stroke, and CV or unexplained death. The upper credible interval (CrI) was 1.75 for noninferiority.

The second primary efficacy endpoint was a one-tailed test of either the difference or the ratio of systemic embolization or ischemic stroke rates 7 days after the implant was placed. The upper CrI was less than 2 for the ratio and less than 0.0275 for the difference.

“PREVAIL efficacy endpoints were never designed to be analyzed without the informative prior from PROTECT AF,” Kar said.

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Kenneth Stein

Demographics in the meta-analysis were well-matched, although the CHA2DS2-VASc score was high in both the device group (3.6) and the control group (3.9).

Five-year analysis showed that patients in the PREVAIL trial had an 18-month rate ratio of 1.33 (95% CrI, 0.78-2.13). The second primary endpoint had an 18-month rate difference of 0.012 (95% CrI, –0.0036 to 0.0275).

The composite endpoint rates were similar between groups, as were the all-stroke and systemic embolism rates. Ischemic stroke was slightly higher in the device arm, although it was not significant. The rate of hemorrhagic stroke was significantly lower in both arms, and the occurrence of CV or unexplained death was lower in the device arm.

Researchers compared the baseline CHA₂DS₂-VASc score in various trials with ischemic stroke risk events.

“If you put all of the clinical trials including PREVAIL, you can see that the endpoints of ischemic stroke rate are actually in accordance to the CHA₂DS₂-VASc score,” Kar said.

There was no difference in all-cause stroke between the two groups in the patient-level analysis. The rate of ischemic stroke or systemic embolization was numerically, but not statistically significant, higher than left atrial appendage closure (HR = 1.7; P = .08). If the procedure-related strokes were excluded, the difference in ischemic stroke or systemic embolization remained nonsignificant (HR = 1.4; P = .3). Nonprocedure-related major bleeding was extremely low in the device arm (HR = 0.48; P = .0003).

The device group had a greater reduction in disabling strokes compared with those in the warfarin group.

“This is very meaningful because the disabling stroke rate was significantly decreased with the device vs. warfarin,” Kar said. “In addition, the reduction of disabling strokes and major bleeding translated into a reduction of mortality in the Watchman device arm in comparison to the [warfarin] arm.”

“The data presented today lend additional credence to the long-term safety and efficacy for the Watchman device,” Kenneth Stein, MD, senior vice president and chief medical officer of rhythm management and global health policy at Boston Scientific, said in a press release. “The totality of the data from both randomized trials and observational studies convincingly demonstrates ischemic stroke reduction similar to that observed with warfarin when accounting for differences in CHA₂DS₂-VASc score.”

In a related editorial, Jacqueline Saw, MD, clinical assistant professor at Vancouver Coastal Health Research Institute, wrote: “The reduction in disabling strokes with Watchman serves as a reminder of the differential functional impact of ischemic and hemorrhagic strokes. Intracranial hemorrhage is a known and accepted complication with [oral anticoagulation] with an annual rate of 0.3% to 0.5% even with direct [oral anticoagulation], and it is reassuring to observe dramatic reduction with LAA [closure]. The substantial reductions of life-threatening bleeds after Watchman implantation beyond the period of antithrombotic requirement likely has substantially contributed to the mortality benefit seen in this analysis. Reduction of cardiovascular and all-cause mortality is a remarkable feat with this device therapy and emphasizes one of the key benefits with LAA [closure], which is reduction of major bleeding and associated complications with lifelong [oral anticoagulation] administration.” – by Darlene Dobkowski

References:

Reddy VY, et al. Late-Breaking Clinical Trials 4. Presented at: TCT Scientific Symposium; Oct. 29-Nov. 2, 2017; Denver.

Reddy VY, et al. J Am. Coll Cardiol. 2017;doi:10.1016/j.jacc.2017.10.021.

Saw J. J Am. Coll Cardiol. 2017;doi:10.1016/j.jacc.2017.10.056.

Disclosures: The PREVAIL and PROTECT AF trials were funded by Boston Scientific. Kar reports he received research grants from and consults for Abbott Vascular and Boston Scientific; served as a member of the advisory board for LAA closure; is the national principal investigator of the Continuous Access Registries; and served as a proctor for Boston Scientific. Stein is an employee of Boston Scientific. Saw reports she has received unrestricted research grant support from Abbott Vascular, AstraZeneca, Boston Scientific, St. Jude Medical and Servier; speaker honoraria from AstraZeneca, Boston Scientific, St. Jude Medical and Sunovion; consultancy and advisory board honoraria from Abbott Vascular, AstraZeneca and St. Jude Medical; and proctorship honoraria from Boston Scientific and St. Jude Medical.