Abstract

Background:

Left ventricular thrombus (LVT) is associated with substantial risk of embolism and mortality. Given the growing use of direct oral anticoagulants for LVT and evolving evidence, we conducted an updated, comprehensive systematic review and meta-analysis comparing their effectiveness and safety with vitamin K antagonists.

Methods:

We systematically searched PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception through the most recent search date for randomized controlled trials and observational studies comparing DOACs with VKAs in adults with imaging-confirmed LVT. Outcomes of interest included LVT resolution, systemic embolic events, all-cause mortality, bleeding events, and composite clinical outcomes. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Statistical heterogeneity was assessed using the I² statistic.

Results:

A total of 29 studies, comprising randomized controlled trials and observational cohorts, were included. Compared with VKAs, DOAC therapy was associated with a numerically higher likelihood of LVT resolution, although this did not reach statistical significance (RR 1.06, 95% CI 0.98–1.14; I² = 48.2%). There was no significant difference in the risk of systemic embolic events between DOACs and VKAs (RR 0.89, 95% CI 0.78–1.03; I² = 5.5%). DOAC use was associated with a lower risk of all-cause mortality (RR 0.84, 95% CI 0.64–1.09; I² = 5.5%); however, this finding was primarily driven by observational data. DOACs were also associated with a lower risk of bleeding events (RR 0.86, 95% CI 0.72–1.03; I² = 16.4%), although this did not reach statistical significance.

Conclusions:

In this updated meta-analysis, DOACs were associated with a numerically higher rate of LVT resolution, although this did not reach statistical significance, and with lower rates of bleeding compared with VKAs, without an increased risk of systemic embolic events. Although a lower risk of all-cause mortality was observed, this finding was primarily driven by observational studies and should be interpreted with caution. These findings support DOACs as a reasonable and potentially safer alternative to VKAs for the management of LVT, while emphasizing the need for adequately powered randomized trials to confirm optimal anticoagulation strategies in this population.

Systematic Review Registration:

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251181379, PROSPERO CRD420251181379.

Introduction

Left ventricular thrombus (LVT) typically develops most commonly after an acute myocardial infarction (MI), in chronic cardiomyopathy with a reduced ejection fraction, or in the context of hypercoagulable states. LVT typically forms within 1–14 days after MI and is associated with higher risks of systemic embolism (stroke/TIA/peripheral embolism), recurrent MI, and death, with many thromboembolic events clustering in the first four months post-MI. Even with anticoagulation, persistent or recurrent thrombus and embolic complications remain clinically significant (1–4).

Historically, vitamin K antagonists (VKAs), most commonly warfarin, have been the standard therapy for LVT with a target INR 2.0–3.0, and a typical treatment duration of 3–6 months adjusted to thrombus resolution, LV recovery, and bleeding risk. This approach is reflected in major guidance, as the American Heart Association (AHA) 2022 Scientific Statement on LVT recommends initiating therapeutic oral anticoagulation for post-MI LVT “typically for 3 months.” The statement also provides practical management suggestions for non-ischemic cardiomyopathy–related LVT (1, 5–7).

From the European perspective, the 2017 ESC STEMI Guideline recommended oral anticoagulation for at least 6 months when LVT is present, with imaging-guided continuation; the more recent 2023 ESC Acute Coronary Syndromes (ACS) Guideline continues to acknowledge anticoagulation for LVT within comprehensive ACS care pathways, with duration individualized and guided by follow-up imaging (4, 8, 9).

In 2025, the ACC/AHA ACS Guideline updated broader ACS management and recognized the evolving evidence around LVT; while VKAs remain the traditional standard (8), contemporary guidance and expert summaries increasingly note that either VKAs or a direct oral anticoagulants (DOACs) may be considered for ∼3–6 months in LVT, acknowledging that high-certainty, LVT-specific randomized evidence is limited (9).

Meanwhile, DOACs, including apixaban, rivaroxaban, dabigatran, and edoxaban, are firmly established in non-valvular atrial fibrillation and venous thromboembolism due to their predictable pharmacokinetics, rapid onset, fewer drug/food interactions, and the absence of routine INR monitoring. These advantages have prompted the growing use of DOACs for LVT. Early observational cohorts, as well as emerging randomized trials, suggest comparable effectiveness to VKAs for thrombus resolution and embolic prevention, although results remain heterogeneous across settings and designs.

Accordingly, this updated systematic review and meta-analysis will synthesize randomized and observational evidence comparing DOACs vs. VKAs for LVT, focusing on thrombus resolution, embolic events, bleeding, and mortality, to inform clinical decision-making and the next iterations of guideline recommendations.

Methods

This systematic review and meta-analysis was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement (10), and the study protocol was registered in PROSPERO (CRD420251181379). The completed PRISMA 2020 checklist is provided in Supplementary Table S1.

Study design and eligibility criteria

We systematically identified randomized and observational studies evaluating the comparative effectiveness and safety of DOACs vs. VKAs in patients with LVT. Eligible studies enrolled adult patients (≥18 years) with LVT confirmed by imaging, including transthoracic or contrast echocardiography, cardiac magnetic resonance imaging, or computed tomography, irrespective of the underlying etiology, such as post–myocardial infarction, non-ischemic cardiomyopathy, or other causes.

Studies were required to evaluate treatment with a DOACs (apixaban, rivaroxaban, dabigatran, or edoxaban) and include a comparator group receiving warfarin or another VKAs. To be eligible, studies had to report at least one clinically relevant outcome, including thrombus resolution on follow-up imaging, systemic embolic events, all-cause mortality, and bleeding events. Randomized controlled trials, prospective or retrospective cohort studies, and case–control studies were included. Case reports, small case series, review articles, editorials, conference abstracts without full data, and non-peer-reviewed literature were excluded.

Data sources and search strategy

A comprehensive literature search was performed in PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from database inception through the most recent search date. The search strategy combined controlled vocabulary terms and free-text keywords related to LVT, direct oral anticoagulants, warfarin, and individual DOAC agents; the complete search strategies for PubMed/MEDLINE, Embase, and Cochrane CENTRAL are provided in the Supplementary Materials (Supplementary Table S2). No restrictions were applied based on year of publication. Only studies published in English were considered.

To ensure completeness, reference lists of included studies and relevant reviews were manually screened. Additional searches were conducted using Google Scholar and selected high-impact cardiovascular and thrombosis journals. The complete electronic search strategy is provided in the Supplementary Appendix S1.

Study selection

All identified records were imported into a reference management system, and duplicate citations were removed. Two reviewers independently screened titles and abstracts to identify potentially eligible studies. Full texts of relevant articles were then reviewed in detail to determine final inclusion. Any disagreements were resolved through discussion, and when necessary, by consultation with a third reviewer. The study selection process is summarized in a PRISMA 2020 flow diagram.

Data extraction

Data extraction was performed independently by two reviewers using a standardized, pilot-tested data collection form. Extracted variables included study characteristics (first author, publication year, country, study design, and setting), patient demographics and LVT etiology, intervention details (type, dose, and duration of DOAC therapy), comparator characteristics (VKA regimen and target INR), reported clinical outcomes, and duration of follow-up.

Where available, additional details on DOAC type, dosing regimens, and treatment duration—including continuation after thrombus resolution were collected. However, reporting of dose-specific outcomes and post-resolution anticoagulation duration was inconsistent across studies, limiting further stratified analyses.

Any discrepancies in data extraction were resolved through consensus, with arbitration by a third reviewer when necessary. The final dataset was cross-checked to ensure accuracy and completeness prior to analysis.

Risk of bias assessment

The methodological quality of included studies was assessed independently by two reviewers according to study design. Randomized controlled trials were evaluated using the Cochrane Risk of Bias tool version RoB 2.0 (11), while observational studies were assessed using the ROBINS-I tool (12). Each study was categorized as having low, moderate (some concerns), or high risk of bias. Disagreements were resolved through discussion or adjudication by a third reviewer. Risk-of-bias assessments were incorporated into the interpretation of findings and into prespecified sensitivity analyses.

Data synthesis and statistical analysis

A qualitative narrative synthesis was conducted for all included studies. Quantitative synthesis was performed when at least two studies reported the same outcome. Given the limited number and size of randomized trials in this field, randomized and observational studies were pooled using random-effects models to provide an overall estimate of treatment effects, while accounting for anticipated clinical and methodological heterogeneity. Prespecified subgroup and sensitivity analyses were performed according to the study design to explore the robustness of the pooled estimates.

Dichotomous outcomes were summarized using risk ratios or odds ratios with corresponding 95% confidence intervals, while time-to-event outcomes were summarized using hazard ratios when available. Statistical heterogeneity was assessed using the Cochran Q test and quantified using the I² statistic, with I² values greater than 50% indicating substantial heterogeneity.

Subgroup and sensitivity analyses

Prespecified subgroup analyses were conducted based on study design (randomized controlled trials vs. observational studies). Sensitivity analyses were performed by excluding studies at high risk of bias and studies with disproportionate influence on pooled estimates. Publication bias was assessed using visual inspection of funnel plots and Egger's regression test, with results presented in the Supplementary Materials (Figures S1–S4).

ResultsStudy selection

The systematic literature search identified 576 records, including 191 from PubMed/MEDLINE, 50 from the Cochrane Central Register of Controlled Trials, and 68 from Embase. After removing 318 duplicate records, 258 unique records were screened by title and abstract. Of these, 227 records were excluded during initial screening as irrelevant to the study question.

A total of 31 full-text articles were assessed for eligibility. Three studies were subsequently excluded at the full-text stage: one conference abstract without complete data and two editorials. This left 29 studies that met the predefined inclusion criteria and were included in the qualitative synthesis and meta-analysis. The study selection process is summarized in the PRISMA 2020 flow diagram (Figure 1).

PRISMA 2020 flow diagram illustrating study selection. A total of 29 studies were included, comprising 7 randomized controlled trials, 1 prospective observational cohort study, and 21 retrospective observational cohort studies.

Characteristics of included studies

A total of 29 studies were included, comprising 7 randomized controlled trials, 1 prospective observational cohort study, and 21 retrospective observational cohort studies, with a combined sample of 5,229 patients with LVT. Of these, 2,074 patients received DOACs and 3,155 received VKAs, as summarized in Table 1.

Study (Year)DesignNDOAC/VKAAgeMale (%)LVT EtiologyImagingDOACDOAC DoseAntiplatelet RegimenFollow-upPrimary OutcomeShah (13)Randomized controlled trial261171/9054.579Post–myocardial infarctionTransthoracic echocardiographyRivaroxaban20 mg once dailyTriple therapy → single antiplatelet therapy (clopidogrel)12 weeksLVT resolutionMansouri (3)Randomized controlled trial5226/2656.585Acute coronary syndromeTransthoracic echocardiographyRivaroxaban20 mg once dailyTriple therapy → dual therapy (DOAC + clopidogrel)3 monthsLVT resolutionYoussef (14)Randomized controlled trial5025/2552.088Post–myocardial infarctionTransthoracic echocardiographyApixaban5 mg twice dailyTriple therapy → single antiplatelet therapy6 monthsLVT resolutionJenab (15)Randomized controlled trial5026/245582ST-elevation myocardial infarctionTransthoracic echocardiographyRivaroxaban20 mg once dailyDual antiplatelet therapy3 monthsLVT resolutionAli (16)Randomized controlled trial3518/1757.180Post–myocardial infarctionTransthoracic echocardiographyApixaban5 mg twice dailyTriple therapy → single antiplatelet therapy3 monthsLVT resolutionAbdelnabi (17)Randomized controlled trial7939/4049.657MixedTransthoracic echocardiographyRivaroxaban20 mg once dailyDual antiplatelet therapy (∼53%)6 monthsLVT resolutionIsa (18)Randomized controlled trial2714/1355.293MixedTransthoracic echocardiographyApixaban5 mg twice daily (dose reduction applied)Not reported12 weeksLVT resolutionAli (16)Retrospective cohort11032/605979MixedEchocardiography/cardiac magnetic resonanceMultiple DOACsStandard dosesSingle antiplatelet therapy predominant1 yearStroke/systemic embolismRobinson (19)Retrospective cohort514185/30058.474MixedTransthoracic echocardiographyMultiple DOACsStandard dosesNot reported351 daysStroke/systemic embolismIqbal (20)Retrospective cohort8422/626289MixedEchocardiography/cardiac magnetic resonanceMultiple DOACs (rivaroxaban, apixaban, dabigatran)Standard dosesSingle antiplatelet therapy 65%; dual antiplatelet therapy 38%3 yearsThromboembolismGuddeti (21)Retrospective cohort9919/806171MixedTransesophageal echocardiographyMultiple DOACsStandard dosesTriple therapy reported in subset10 monthsStroke/bleedingDaher (22)Retrospective cohort5917/426283Post–myocardial infarctionTransesophageal echocardiographyApixaban, dabigatran, rivaroxabanDose adjustedAspirin 58.8%; P2Y12 inhibitor 64.7%3 monthsLVT resolutionXu (23)Retrospective cohort8725/6261.576MixedTransesophageal echocardiographyRivaroxaban or dabigatranStandard dosesNot reported2.4 yearsStroke/systemic embolismMihm (24)Retrospective cohort10833/756271Post–myocardial infarctionEchocardiography/cardiac magnetic resonanceApixaban or rivaroxabanStandard dosesAspirin 57.6%; P2Y12 inhibitor 21.2%6 monthsStroke/systemic embolismJones (25)Prospective cohort10141/60Not reportedNot reportedPost–myocardial infarctionTransthoracic echocardiographyApixaban or rivaroxabanStandard dosesTriple therapy 68%; dual therapy 24%Not reportedNot reportedWilleford (26)Retrospective cohort15122/1295680MixedTransthoracic echocardiographyApixaban or rivaroxabanStandard dosesDual therapy 37%; triple therapy 19%12 monthsLVT resolutionAlbabtain (27)Retrospective cohort6328/355991Post–myocardial infarctionTransthoracic echocardiographyRivaroxaban20 mg once daily (reduced to 15 mg in some patients)Dual antiplatelet therapy254 daysComposite outcomeZhang (28)Retrospective cohort6433/3160.873ST-elevation myocardial infarctionTransthoracic echocardiographyRivaroxaban20 mg once dailyTriple therapy → dual therapy25 monthsLVT resolutionLiang (29)Retrospective cohort12856/7255.188ST-elevation myocardial infarctionTransthoracic echocardiographyRivaroxaban or dabigatranMixed dosingTriple therapy common12 monthsLVT resolutionHerald (30)Retrospective cohort433134/2996683LVTTransthoracic echocardiographyMultiple DOACsStandard dosesP2Y12 inhibitor ∼45%3.4 yearsIschemic compositeZhou (28)Retrospective cohort240111/1295588Post–myocardial infarctionTransthoracic/transesophageal echocardiographyRivaroxaban or dabigatranStandard dosesAspirin 42.3%; P2Y12 inhibitor 54.1%1 yearLVT resolutionAl-Maimoony (31)Retrospective cohort302183/119Not reportedNot reportedLVTNot reportedApixaban or rivaroxabanDose adjustedAspirin 76.5%; clopidogrel 39.3%12 monthsLVT resolutionPaiva (32)Retrospective cohort17199/7259.883LVTNot reportedMultiple DOACsStandard dosingTriple therapy 14.6%185 daysLVT resolution

Summary of studies included (n = 29).

Age is reported as mean or median as provided in the original studies.

Standard therapeutic DOAC dosing refers to apixaban 5 mg twice daily and rivaroxaban 20 mg once daily, unless otherwise specified. Dose adjustments were applied in selected studies based on clinical criteria.

Antiplatelet regimens were extracted when reported; NR indicates not reported.

Across the included studies, DOAC dosing was generally consistent with standard therapeutic regimens used for thromboembolic indications. Apixaban was most commonly administered at 5 mg twice daily, with dose reductions applied in selected patients, while rivaroxaban was typically prescribed at 20 mg once daily or 15 mg once daily in patients with renal impairment or increased bleeding risk.

Concomitant antiplatelet therapy was reported in several studies, particularly among post-MI and ACS populations. In these settings, dual antiplatelet therapy (DAPT) was commonly reported, and some studies described short-term triple antithrombotic therapy. However, detailed information regarding antiplatelet regimens and their duration was inconsistently reported across studies.

Risk of bias in included studies

Overall, randomized controlled trials were judged to have low to some concerns of bias across most domains. In contrast, the majority of observational studies were rated as having moderate to serious risk of bias, primarily due to confounding and selection bias. Detailed risk-of-bias assessments for individual studies are presented in Supplementary Table S3A,B.

LVT resolution

Across 28 included studies, DOAC therapy was associated with a numerically higher rate of LVT resolution compared with VKAs, although this did not reach statistical significance (overall RR 1.06, 95% CI 0.98–1.14), with moderate heterogeneity (I² = 48.2%). Subgroup analysis by study design demonstrated a consistent direction of effect in observational studies (RR 1.07, 95% CI 0.96–1.20; I² = 46.5%) and randomized controlled trials (RR 1.02, 95% CI 0.94–1.10; I² = 17.9%), with no significant interaction between subgroups. These findings suggest a modest improvement in thrombus resolution, although this did not reach statistical significance (Figure 2).

LVT resolution.

Systemic embolic events

No significant difference was observed between DOACs and VKAs in the risk of systemic embolic events. The pooled analysis demonstrated comparable outcomes between treatment groups (RR 0.89, 95% CI 0.78–1.03), with low heterogeneity (I² = 5.5%). Results were consistent across observational cohorts and randomized trials, indicating similar effectiveness of DOACs and VKAs in preventing embolic complications in patients with LVT (Figure 3).

Systematic embolism.

All-Cause mortality

DOAC use was associated with a numerically lower risk of all-cause mortality compared with VKAs, although this did not reach statistical significance (RR 0.84, 95% CI 0.64–1.09), with minimal heterogeneity (I² = 36.4%) (Figure 4).

All cause-mortality.

Bleeding outcomes

Patients treated with DOACs had a numerically lower rate of bleeding events than those receiving VKAs, although this difference did not reach statistical significance (RR 0.86, 95% CI 0.72–1.03). Heterogeneity across studies was low to moderate (I² = 16.4%). These findings were directionally consistent across study designs (Figure 5).

Bleeding outcomes.

Discussion

This updated systematic review and meta-analysis synthesizes contemporary randomized and observational evidence comparing DOACs with VKAs for the treatment of LVT. By integrating data from 29 studies encompassing diverse clinical settings and LVT etiologies, the analysis provides a comprehensive assessment of thrombus resolution, embolic events, major bleeding outcomes, and all-cause mortality in routine practice. The primary findings indicate that DOAC therapy was associated with a numerically higher rate of LVT resolution compared with VKAs, although this did not reach statistical significance, along with numerically lower risks of bleeding and all-cause mortality, without an increased risk of systemic embolic events.

The observed trend toward improved thrombus resolution with DOACs suggests at least comparable antithrombotic effectiveness relative to warfarin in this setting. Importantly, this association remained directionally consistent across prespecified subgroup analyses, including randomized controlled trials and observational studies. This benefit was observed despite substantial heterogeneity in patient populations, imaging modalities, anticoagulant regimens, and follow-up durations. The consistency of effect direction across sensitivity analyses supports the robustness of the pooled estimates. At the same time, the absence of a significant difference in systemic embolic events between treatment strategies reinforces the clinical safety of DOACs for embolic prevention in LVT, a key concern that has historically limited their adoption.

When placed in the context of earlier literature, these findings align with and extend prior observational reports and mechanistic understanding of LVT formation following myocardial infarction, as well as contemporary clinical guidance on LVT management (1, 2). Historically, warfarin has been the standard therapy for L