Left atrial appendage occlusion (LAAC) remains non-inferior to non vitamin-K-antagonists (NOACs) for the prevention of major cardiovascular, neurological or bleeding events in patients with non-valvular atrial fibrillation (AF) at long-term follow-up.
These are four-year findings of the PRAGUE-17 clinical trial, presented during a late-breaking clinical trial session at the Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021, 4–6 November, Orlando USA and virtual) by study author Pavel Osmancik (Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic) and published simultaneously in the Journal of the American College of Cardiology (JACC).
In PRAGUE-17, 201 patients with non-valvular AF (at high risk of stroke) were randomised to undergo LAAC with either the Amplatzer Amulet device (Abbott) or the Watchman/Watchman Flex device (Boston Scientific); while another 201 were randomised to receive a NOAC (apixaban preferably, but could also be rivaroxaban or dabigatran).
In the LAAC group, patients received clopidogrel and aspirin (dual antiplatelet therapy) for three months before undergoing transoesophageal echocardiogram (TOE). At this time point, clopidogrel was discontinued but the aspirin was continued indefinitely. However, this regimen could be individualised (i.e. shortened) if the patient had a high risk of bleeding.
The primary endpoint was a component of stroke or transient ischaemic attack, systemic embolism, clinically significant bleeding, or significant periprocedural or device-related complications.
Osmancik and colleagues report that the 402 patients enrolled in the study had an average age of 73.3±7 years, 65.7% were male, with a CHA2DS2-VASc score of 4.7+1.5, and HASBLED score of 3.1+0.9. After 3.5 years median follow-up (1,354 patients-years), LAAC was found to be non-inferior to NOAC for the primary endpoint by modified intention-to-treat (subdistribution hazard ratio[sHR] 0.81, 95% confidence interval [CI] 0.56‒1.18; p=0.27; p for noninferiority=0.006).
For the components of the composite endpoint, the study’s authors report that the corresponding sHRs (and 95% CIs) were 0.68 (0.39‒1.20; p=0.19) for cardiovascular death, 1.14 (0.56‒2.30; p=0.72) for all-stroke/TIA, 0.75 (0.44-1.27; p=0.28) for clinically-relevant bleeding, and 0.55 (0.31‒0.97; p=0.039) for non-procedural clinically-relevant bleeding. The primary endpoint outcomes were similar in the per-protocol [sHR 0.80 (95% CI 0.54‒1.18), p=0.25] and on-treatment [sHR 0.82 (95% CI 0.56-1.20), p=0.30] analyses.
Writing in JACC Osmancik and colleagues conclude that among non-valvular patients with AF and at high risk for stroke and bleeding, the non-inferiority of LAAC to NOAC relative to the composite of cardioembolic events, cardiovascular death, significant procedure or device-related complications, or clinically-relevant bleeding, was maintained during long-term follow-up. “The rate of non-procedural clinically relevant bleeding was significantly reduced with LAAC compared with NOAC therapy, but the study was underpowered to detect differences in stroke rate,” they add, noting that the curves of clinically relevant bleeding appear to separate at around six months.