RCTs are widely regarded as the most accurate way of answering research questions. To the best of our knowledge, until recently, literature has been limited to observational studies and there is only one RCT to compare the efficacy and safety of rivaroxaban vs. Warfarin in post-ACS patients with LVT. Our study reveals several key findings. We observed no statistically significant difference in thrombus resolution, thrombus size improvement, risk of bleeding, or rehospitalization in patients treated with warfarin compared to those treated with rivaroxaban. Additionally, no embolic events, stroke, or Major Adverse Cardiovascular Events (MACE) were observed in either group. Among patients without complete resolution of thrombus, all mobile thrombi changed into immobile, and all round LVTs transformed into mural in both the rivaroxaban and warfarin groups. Furthermore, our results indicated that a greater proportion of subjects in the warfarin group achieved TTR ≥ 50%, correlating with a significantly higher rate of thrombus resolution. Overall, our findings suggest that rivaroxaban, is non-inferior to Warfarin for LVT management in ACS patients. These results are consistent with results seen in some prior observational studies and the recent clinical trial [12].

Although LVT can occur in settings other than infarction, its incidence is relatively high following an ST-elevation myocardial infarction (STEMI), and the medical management of LVT is very challenging due to its high risk of embolization and ischemic stroke. Anticoagulation therapy is one of the main parts of LVT management. Current guidelines (ESC, ACCF/AHA) primarily involve vitamin K antagonist (warfarin) for up to 3 months according to ACCF/AHA, with the Class IIa of recommendation and up to six months according to ESC, with the class IIa of recommendation, for treatment of post-ACS, LVT [6,16]. Concurrently, direct oral anticoagulants (DOACs) are advised for patients exhibiting poor control with warfarin. However, in recent years, the absence of a requirement for frequent monitoring, freedom from multiple drug interactions, and dietary restrictions increased the off-label use of DOACs among patients with LVT [17].

A recent meta-analysis on the safety and efficacy of DOAC vs. Warfarin in patients with LVT suggested that DOACs are non-inferior to Warfarin in terms of thrombus resolution, risk of bleeding, stroke and systemic embolization (SSE), and mortality which is congruent with our results [18]. Additionally, results from Jones et al. showed increased thrombus resolution with DOACs compared to warfarin [19].

Abdelnabi et al. recently conducted a non-LVT trial to compare efficacy and safety of rivaroxaban with Warfarin. They have prescribed 20 mg rivaroxaban daily for their subjects. Their patients were a combination of those with ACS and other cardiomyopathies. The results of this study showed that rivaroxaban was non-inferior to Warfarin with even faster resolution of thrombus in rivaroxaban group. They also reported more embolic events, stroke and major bleeding with Warfarin compared to rivaroxaban. In our study we showed that rivaroxaban is non-inferior to Warfarin for management of LVT and our results are consistent with this RCT [12].

LVT characteristics including mobility and morphology, which can be helpful in predicting the risk of embolization, were rarely discussed and assessed in previous studies. There are pieces of evidence that mural thrombus tends to be less mobile and has lower risk of embolization compared to round or protuberant thrombus [14,15]. In our study all of the round thrombi, those without complete resolution, transformed into mural thrombus in both rivaroxaban and warfarin groups.

In terms of thrombus size, a significant size reduction was detected in both warfarin and rivaroxaban groups with no statistically significant difference between groups. On the other hand, analysis of the difference in thrombus size changes was significantly higher in the warfarin group compared to the rivaroxaban group, and we think that the non-significantly greater baseline thrombus size in the warfarin group seems to be the reason.

Jugdutt et al. reported the occurrence of embolic events is associated with increased mobility of LVT in patients with acute MI [20]. Also, Oh et al. showed that thrombus mobility is the most important predictor of thrombus resolution and the first-ranked discriminator for embolic events [14]. Results from multiple studies and a recent meta-analysis performed by Dalia et al. found that there is no statistically significant difference in risk of stroke or systemic embolization (SSE) between Warfarin and DOACs, including rivaroxaban [18]. In our study all of the mobile LVTs, changed into immobile after intervention in both warfarin and rivaroxaban groups and the mobility change was statistically significant only in the warfarin group. The patients with resolved thrombus were not included in the pre and post-test analysis of mobility and morphology (because of the lack of data after thrombus resolution); So, because of the small number of patients in this analysis, it seems that we cannot conclude that Warfarin is more efficient than rivaroxaban in turning mobile LVT into immobile.

Although the results of our study support previous literature on the use of DOACs for the treatment of LVT, our study may have some limitations. The relatively small sample size may lead to low statistical power. Future studies can overcome this limitation by increasing their sample sizes. Also, another limitation is its single-center design, which may impact the generalizability of the findings. Future studies conducted across multiple centers are warranted to validate and extend our observations.

We also suggest to measuring the thrombus characteristics by more novel modalities including three-dimensional echocardiography, contrast enhanced TTE, or cardiac magnetic resonance imaging for future studies.