Non-valvular atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a considerable risk of stroke, systemic embolism (SE), heart failure and all-cause mortality [
1]. Without oral anticoagulation, there is fivefold increased age-adjusted risk of AF-associated stroke [
2]. For several decades, OAC with vitamin K antagonist (VKA) was the standard therapy in reducing risks of AF-associated stroke and SE, with a relative risk reduction of 62% [
3]. The CHA
2DS
2-VASc score is the risk score most commonly used to determine the indication for anticoagulation. It represents a further development of the established CHADS
2 score (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus and prior stroke or transient ischaemic attack), and adds further stroke risk factors (vascular disease in the form of prior myocardial infarction, plaque in aorta and peripheral artery disease, age 65–74 years and female sex) [
4]. According to the current American and European guidelines, patients with a CHA
2DS
2-VASc score ≥ 2 have an increased stroke risk necessitating anticoagulation therapy [
5,
6]. Since VKA therapy has several limitations, such as inter-patient and intra-patient variability of drug dose, regular monitoring to ensure therapeutic anticoagulation within a target international normalised ratio (INR) range (2.0–3.0) is required [
7]. Time in therapeutic range (TTR) ≥ 65%, to ensure adequate stroke risk prevention, is rarely achieved, even in large trials [
8‐
11]. The drug compliance and TTR are less optimal in real life than in RCTs. Non-vitamin K antagonist oral anticoagulants (NOACs) have therefore been developed with direct inhibition of the coagulation cascade and without the need for routine coagulation monitoring. The NOAC group includes the direct thrombin inhibitor dabigatran and the direct factor Xa (FXa) inhibitors apixaban, edoxaban and rivaroxaban. In large clinical phase III trials, all four NOACs were effective as VKA in preventing stroke and SE with lower rates of haemorrhagic stroke [
8‐
11]. A meta-analysis of all four NOACs demonstrates that the risk of stroke or SE was reduced by 19% compared to VKA (relative risk ratio 0.81; 95% confidence interval 0.73–0.91,
p < 0.0001). The NOACs also show similar or lower rates of major or clinically relevant non-major bleeding events [
12]. Consequently, all four NOACs were approved by the US Food and Drug Administration (FDA) in 2010 (dabigatran), 2011 (rivaroxaban), 2012 (apixaban) and 2015 (edoxaban) for patients with AF [
13].
The frequency of left atrial (LA)/left atrial appendage (LAA) thrombus formation in patients with AF varies depending on anticoagulation (non vs. anticoagulation), type of treatment (concomitant treatment with acetylsalicylic acid vs. OAC alone), targeted INR values and TTR, type of AF (paroxysmal AF vs. non-paroxysmal AF), LAA morphology (chicken wing vs. non-chicken wing), LA size, increased left ventricular end-diastolic volume, ejection fraction (EF), inappropriate duration of anticoagulation < 3 weeks, metabolic syndrome, diabetes mellitus, CHADS
2 and CHA
2DS
2-VASc score [
14‐
24]. Retrospective studies revealed frequencies of LA/LAA thrombus in AF patients without anticoagulation therapy in the range of 13.0–19.0% [
18,
24,
25]. The EMANATE trial, a randomised, active-controlled, open-labelled study showed a prevalence of thrombus formation in anticoagulation-naive AF patients of 7.1% [
26]. The frequencies of thrombus formation under treatment with VKA vary between 3.5% and 17.8% [
16,
17,
20,
21,
27]. Controlled therapeutic anticoagulation with VKA (INR 2.0–3.0) exhibited the lowest rates of intracardiac thrombus formation among retrospective studies to be of 0.6–7.7% [
15,
19,
28].
The gold standard and most simple method for the exclusion of LA/LAA thrombus is TEE. In AF patients of more than 48-h duration, insufficient or no anticoagulation, therapeutic anticoagulation for at least 3 weeks prior to cardioversion or TEE is recommended. However, little is known about the frequency of LA/LAA thrombus under anticoagulation with NOACs in comparison to VKAs. The objective of this meta-analysis was thus to evaluate the frequency of LA/LAA thrombus formation in patients with AF under treatment with non-vitamin K oral anticoagulants in comparison to vitamin K antagonists.