PRAGUE-17 Supports LAAO Device Noninferiority to DOACs in AF

Heidi Splete

June 23, 2020

Left atrial appendage closure was noninferior to use of direct oral anticoagulants for the prevention of atrial fibrillation (AFib)–related events in high-risk patients, based on data from 402 adults.

Given the limitations of vitamin K antagonists for preventing stroke in AFib, "a novel site-specific therapeutic alternative, mechanical left atrial appendage occlusion [LAAO], entered clinical practice," but has not been compared with current safe and effective oral anticoagulants, wrote Pavel Osmancik, MD, of University Hospital Kralovske Vinohrady, Prague, and colleagues.

In a study published in the Journal of the American College of Cardiology, the researchers randomized 201 moderate- or high-risk adults with nonvalvular AFib to LAAO and another 201 to direct oral anticoagulants (DOAC).

Patients in the LAAO group underwent transesophageal echocardiography to exclude left atrial thrombi and underwent implantation with Boston Scientific's Watchman, Watchman-FLX, or Abbott's Amulet devices. Patients in the DOAC group received rivaroxaban, apixaban, or dabigatran at the manufacturer-recommended dose.

The primary outcome was a composite of complications related to procedures or devices, thromboembolic events (including stroke), and clinically significant bleeding. After an average of 20 months follow-up, 35 patients in the LAAO group and 41 in the DOAC group met the primary outcome (11% per 100 patient-years vs. 13% per 100 patient-years).

In addition, no differences appeared between the groups for the endpoint components of all-stroke/transient ischemic attack event (subdistribution hazard ratio, 1.00), clinically significantly bleeding (sHR, 0.81), or cardiovascular death (sHR, 0.75).

Nine patients experienced major complications related to LAAO, including clinically significant bleeding (sHR, 0.81; 95% CI, 0.44-1.52) and cardiovascular death (sHR, 0.75; 95% CI, 0.34-1.62). Major LAAO-related complications occurred in nine (4.5%) patients, with a short-term (up to 7 days or hospital discharge) complication rate of 2.1% and a 2.7% late complication rate. The late complications included three pericardial effusions, one of which resulted in death, the researchers wrote.

The study findings were limited by several factors, including the inability to assess the differences among the components of the composite primary endpoint. For example, "Regarding the primary endpoint, stroke reduction may be more important than bleeding reduction," the investigators wrote.

The results were strengthened, however, by the enrollment of a high-risk AF population and is the first known randomized trial to compare percutaneous LAAO and DOACs for stroke prevention in this group. But the late complication rate of 2.7% is "suboptimal" and safety issues reinforce the need for refinement of operator technique and device technology with LAAO, they concluded.

"Important Step Forward," With Caveats

"How LAAO might stack up against DOAC therapy has remained an open question: Compared with warfarin, DOACs are easier to use and are associated with a reduction in mortality, driven by a substantially lower risk of intracranial hemorrhage and fatal bleeding," wrote Matthew J. Price, MD, of the Scripps Clinic in La Jolla, Calif., and Jacqueline Saw, MD, of Vancouver General Hospital, in an accompanying editorial.

Previous studies of LAAO have shown a reduced risk of gastrointestinal bleeding, but procedure hazards interfered with long-term benefits, they said. The current study findings of similar rates of stroke and lower bleeding rates with LAAO, compared with DOAC, "are provocative given the clinical consensus that DOACs are safer, well tolerated, and generally better than warfarin, which was an easy target for transcatheter LAAO, given warfarin's extensive limitations," the editorialists wrote. Although the findings lend support to the use of LAAO, clinicians should consider several caveats such as the inclusion of patients who were "not optimal candidates for long-term OAC but were selected because they were at high risk for bleeding or because OAC treatment had already failed."

However, "despite its imperfections, PRAGUE-17 is an important step forward and reinforces the role of transcatheter LAAO as a stroke-prevention strategy for patients with [AFib] at high risk of bleeding or medical treatment failure, even in the modern era of the DOACs," they concluded. "Going forward, successful enrollment in ongoing and planned clinical trials while avoiding off-label procedures will be critical to define the appropriate use of transcatheter LAAO in expanded patient populations."

The study was supported by the Ministry of Health of the Czech Republic. Dr. Osmancik disclosed speaking honoraria from Bayer and Abbot. Dr. Price's financial disclosures included honoraria, speaker bureau fees, and/or research grants from Abbott Vascular, AstraZeneca, Boston Scientific, Chiesi USA, Daiichi Sankyo, and Medtronic. Dr. Saw disclosed receiving unrestricted research grant support several Canadian research institutes and fees and honoraria from AstraZeneca, Abbott Vascular, Boston Scientific, and Servier, among other drug companies.

SOURCES: Osmancik P et al. J Am Coll Cardiol. 2020;75:3122-35; Price MJ, Saw J. J Am Coll Cardiol. 2020;75:3136-9.

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