A systematic review and meta-analysis of eight trials comparing left atrial appendage closure (LAAC) to oral anticoagulation in patients with atrial fibrillation (AF) has shown similar rates of stroke and major bleeding between the two approaches, but the catheter-based treatment was linked to a higher risk of ischaemic stroke and a lower risk of non-procedural bleeding.
Claudio Laudani (University of Catania, Catania, Italy) and colleagues, detailing the findings of their analysis in JAMA Cardiology, write that their study does not support LAAC as a first-line strategy for stroke prevention within this population.
LAAC is seen as an alternative to oral anticoagulation to prevent stroke in AF patients and involves a minimally invasive procedure to implant a device into the left atrial appendage, an intracardiac site at which the majority of thrombi form in patients with AF. Perceived advantages of the device-based therapy include a reduced need for long-term anticoagulation, which can be particularly beneficial if patients are unlikely to adhere to medication in the long term.
The procedure has gained prevalence in recent years—particularly in the USA—though an absence of consistent evidence from randomised trials has prompted guideline committees to assign a low class of recommendation for the therapy, Laudani and colleagues note in their paper. Moreover, two recent trials comparing LAAC to oral anticoagulation—CLOSURE-AF and CHAMPION-AF—arrived at divergent conclusions over the optimal approach.
Through their analysis, Laudani and colleagues selected trials randomising AF patients to either LAAC or oral anticoagulation, looking at primary outcomes of trial-defined stroke and major bleeding. Secondary outcomes included the composite of cardiovascular death, stroke, or systemic embolism, single components of the composite outcome, all-cause death, ischaemic and haemorrhagic stroke, and non-procedural major bleeding.
After screening, eight trials—PREVAIL, PROTECT AF, PRAGUE-17, WATCH TAVR, OPTION, TAVI-LAAO, CLOSURE-AF and CHAMPION-AF—were included in the meta-analysis, comprising a total of 7,434 patients. In the trials’ intervention arms, Watchman (Boston Scientific) was used in 3,531 patients (90.6%), with Watchman-FLX being the most common iteration, while 350 (9%) patients received an Amulet (Abbott), and 17 (0.5%) a Lambre device (Lifetech Scientific).
Laudani and colleagues report that, at a weighted mean follow-up of 37.9 months, catheter-based LAAC was associated with similar stroke (incidence rate ratio [IRR], 1.08; 95% confidence interval [CI], 0.82-1.41) and major bleeding rates (IRR, 0.96; 95% CI, 0.81–1.14) compared with oral anticoagulation, with low heterogeneity for both endpoints.
Catheter-based LAAC was associated with significantly higher rates of ischaemic stroke (IRR, 1.34; 95% CI, 1.01–1.77) and lower risk of nonprocedural major bleeding (IRR, 0.73; 95% CI, 0.58-0.92). No significant differences between groups were detected for the composite endpoint of cardiac death, stroke, or systemic embolism and any other secondary endpoints.
“Although the rates of stroke and major bleeding appear to be similar between the groups, our analysis also highlighted a significant 27% reduction in non-procedural major bleeding rates in patients undergoing LAAC and a 34% increase in ischaemic stroke,” Laudani and colleagues write in their discussion of the findings.
Protocols of the included trials prespecified a reduced intensity in antithrombotic therapy over time in patients undergoing LAAC, they noted, as a possible explanation for the reduction in non-periprocedural major bleeding. However, they add, LAAC may fail to protect from other sources of systemic thromboembolism, whilst the device itself may also represent a source of thrombosis and potential embolism.
Laudani and colleagues note that there are some limitations to consider when weighing up the findings, including reliance on study-level data rather than individual patient data, and the potential for heterogeneity to impair the reliability of results.
“In patients with AF at moderate to high risk of stroke, catheter-based LAAC resulted in similar rates of overall stroke and major bleeding compared with oral anticoagulation but was associated with a significantly higher risk of ischaemic stroke and a lower risk of non-procedure-related major bleeding,” Laudani et al conclude. “These findings suggest that the net clinical benefit of catheter-based LAAC relative to oral anticoagulation remains uncertain and do not support its routine use as a first-line strategy for stroke prevention in this population. Additional studies are needed to assess the applicability of these findings to patients with contraindications to oral anticoagulation.”
