Left Atrial Appendage Occlusion Versus Direct Oral Anticoagulants in the Prevention of Ischaemic Stroke in Patients with Atrial Fibrillation.

Introduction Existing randomised controlled trials assessing the safety and efficacy of left atrial appendage occlusion (LAAO) in atrial fibrillation (AF) were of relatively small sample size, or included patients who could receive oral anticoagulant treatment after device implantation. We compared the outcomes of patients with newly diagnosed AF who received percutaneous LAAO or direct oral anticoagulants (DOAC) treatment, in a large population from a global federated health network (TriNetX). Methods Patients with AF treated with percutaneous LAAO were matched with those treated with DOAC between 1st December 2010 and 1st October 2018. Outcomes were all-cause mortality, ischaemic stroke and intracranial haemorrhage (ICH) at 5 years. Results We included 200 patients with AF, who received either LAAO or DOAC. The risk of all-cause mortality, ischaemic stroke and ICH at 5 years was not significantly different between the two groups (Risk Ratio [RR] for all-cause mortality: 1.52, 95% confidence interval (CI): 0.97- 2.38, RR for ischaemic stroke: 1.09, 95% CI: 0.51- 2.36, and RR for ICH: 1.0, 95% CI: 0.44- 2.30). Conclusion Patients newly diagnosed with AF, eligible for DOAC, showed similar 5-year risk of death, ischemic stroke, and ICH when comparing those who underwent percutaneous LAAO to those receiving DOAC. Future randomised controlled trials are needed to confirm the findings and advise changes in guidelines.

Atrial fibrillation and stroke: State-of-the-art and future directions.

Atrial fibrillation (AF) and stroke remain a major cause of morbidity and mortality. The two conditions shared common co-morbidities and risk factors. AF-related strokes are associated with worse clinical outcomes and higher mortality compared to non-AF-related. Early detection of AF is vital for prevention. While various scores have been developed to predict AF in such a high-risk group, they are yet to incorporated into clinical guidelines. Novel markers and predictors of AF including coronary and intracranial arterial calcification have also been studied. There are also ongoing debates on the management of acute stroke in patients with AF, and those who experienced breakthrough stroke while on oral anticoagulants. We provided an overview of the complex interplay between AF and stroke, as well as the treatment and secondary prevention of stroke in AF. We also comprehensively discussed the current evidence and the ongoing conundrums, and highlighted the future directions on the topic.

A review of emerging factor XI inhibitors.

INTRODUCTION: Whilst the introduction of direct oral anticoagulants (DOACs) has improved the prevention of thromboembolic events, there is still a need for safer anticoagulants. This is particularly so, for specific populations of patients, such as those with an increased bleeding risk or those with severely reduced kidney function. People with Factor XI (FXI) deficiency are at reduced risk of thromboembolic events, without an increased risk of spontaneous bleeding. FXI inhibition, therefore, presents the ideal target for novel anticoagulants. AREAS COVERED: In this review, we provide an overview of the currently available anticoagulants and the emerging FXIa inhibitors in clinical trials. The need for availability of novel anticoagulants and the potential issues that will hinder the development and marketing of factor XIa inhibitors is also discussed. EXPERT OPINION: Evidence suggests that FXI inhibition presents a promising drug target for novel anticoagulation therapies. The FXIa inhibitors in development have advantages over DOACs with lower renal clearance and long half-lives. Overall, FXI inhibition presents a promising target, it is likely that the clinical use of FXIa inhibitors is on the horizon.