What data are available on apixaban for treatment of left ventricular thrombus?

Introduction
Left ventricular thrombus (LVT) formation is primarily attributed to a combination of 3 factors: stasis due to reduced left ventricular (LV) function, endocardial injury, and hypercoagulability, also known as Virchow’s triad.1 The extent of contribution of each factor depends on the cause of the myocardial dysfunction and its duration. Overall, the prevalence of LVT in the general population is low but is frequently observed in patients who experience an ST-segment elevation myocardial infarction (STEMI) and is correlated with the degree of myocardial damage.1,2 In anterior STEMI, the incidence is highly variable, ranging from 4 to 39%, while lower rates (5%) have been observed in patients with anterior non-STEMI. Left ventricular thrombus is also less common in patients who experience a non-anterior MI compared to an anterior MI.2 The time to patient presentation after the onset of chest pain (early versus after 12 hours) may also significantly impact the degree of myocardial damage. In patients with dilated cardiomyopathy (DCM), the incidence of LVT ranges from 11 to 44%.1,2 In order to reduce the risk of embolic complications from LVT, appropriate anticoagulation is critical in this patient population;1,3,4 however, the management of LVT remains challenging, especially with limited organizational guidance available.1

Reperfusion strategies such as percutaneous coronary intervention (PCI) have reduced, but not eliminated the risk of LVT formation.1 According to the 2022 American Heart Association (AHA) scientific statement on the management of patients at risk for and with LVT, the risk of LVT formation after MI is highest within the first month; the risk of recurrent LVT is considered reasonably high within the first 3 months after MI. The AHA suggests oral anticoagulation typically for a 3-month period following MI, based on reasonable evidence. Until further data are available, the AHA recommends repeat imaging after 3 months to assess thrombus resolution. In patients who develop an LVT in the setting of a non-recent MI (e.g., >3 months) or ischemic cardiomyopathy, a duration of 3 to 6 months of anticoagulation is recommended. The 2025 American College of Cardiology (ACC) and American Heart Association (AHA) guideline for the management of patients with acute coronary syndromes (ACS) similarly states that the majority of patients with LVT will require anticoagulation for at least 3 months, with additional imaging to assess residual thrombus and determine if a longer course is needed.5 A 2021 AHA/American Stroke Association (ASA) guideline for the prevention of stroke in patients with stroke and transient ischemic attack (TIA) also recommends anticoagulation for at least a 3-month period in patients with LVT.6

Although oral vitamin K antagonists (VKAs) (e.g., warfarin) are typically used for the treatment and prevention of LVT, the 2022 AHA statement on the management of LVT considers treatment with full-dose direct oral anticoagulants (DOACs) a reasonable alternative to treatment with oral VKAs with a target international normalized ratio (INR) of 2 to 3, as warfarin requires dietary restrictions, frequent INR monitoring, and interactions that are not a concern with DOAC therapy.1 Although DOACs are indicated as a potential alternative to VKA therapy, the 2022 AHA statement does not state a particular DOAC agent (e.g., apixaban, rivaroxaban, dabigatran) for use.

As a direct, reversible, and selective inhibitor of factor Xa, the DOAC, apixaban, indirectly inhibits platelet aggregation induced by thrombin, therefore decreasing thrombin generation and development.7 According to its prescribing information, apixaban is indicated for the reduction of the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF), treatment of deep vein thrombosis (DVT) or pulmonary embolism (PE), and for reduction of the risk of recurrence of DVT or PE. The recommended dose of apixaban for the treatment of DVT and PE is 10 mg orally twice daily for 7 days, followed by 5 mg twice daily. For prophylaxis of DVT following hip or knee replacement surgery, the recommended dose of apixaban is 2.5 mg orally twice daily, with a duration of 35 days of treatment recommended for hip surgery, and 12 days for knee surgery. To reduce the risk of stroke and systemic embolism in patients with nonvalvular AF, the recommended dose is 5 mg by mouth twice daily, with 2.5 mg twice daily recommended for patients with at least 2 of the following characteristics: age ≥80 years, body weight ≤60 kg, and serum creatinine ≥1.5 mg/dL.

This FAQ aims to summarize the available direct comparative data on apixaban use for treatment of LVT.

Evidence from Randomized Controlled Trials
Although numerous meta-analyses have been published evaluating DOACs for treatment of LVT,8-14 only one thus far has focused on published randomized controlled trials (RCTs).15 This meta-analysis (MA) included 5 small RCTs: REWARF-STEMI (2024), Alcalai et al (2021), No-LVT (Abdelnabi et al 2021), Youseff et al (2023), and Isa et al (2021), which evaluated DOACs versus warfarin in patients with STEMI complicated by LVT.15-19 The DOACs evaluated in these studies were apixaban (44%) and rivaroxaban (56%) compared to warfarin therapy (targeted to an INR of 2 to 3 unless otherwise specified), plus additional antiplatelet agents. Specifics on each study include:

  • In Alcalai et al, a 3-month, multicenter, open-label RCT of patients who experienced an anterior MI, 18 patients were randomized to apixaban 5 mg twice daily and 17 to warfarin therapy for.16 LVT presence and size was evaluated after 3 months of anticoagulation. Patients in the apixaban arm received a reduced apixaban dose of 2.5 mg twice daily if they were ≥80 years of age, weighed ≤60 kg, or had a serum creatinine (SCr) of ≥1.5 mg/dL. Antiplatelets were given based on physician discretion.
  • In Youssef et al, a 6-month, multicenter, open-label RCT of patients who experienced anterior MI, 11 patients were randomized to apixaban 5 mg twice daily, and 10 to warfarin therapy; antiplatelet therapy was prescribed based on physician discretion.17 Anticoagulation was routinely given for 3 months and extended if there was not complete LVT resolution at 3-month follow-up.
  • In Isa et al, 24-month, single-blinded RCT of patients in Malaysia, 14 patients were randomized to apixaban 5 mg twice daily and 13 to warfarin.18 Patients in the apixaban arm received a reduced apixaban dose of 2.5 mg twice daily if they were ≥75 years of age, weighed ≤60 kg, or had a SCr of ≥1.5 mg/dL. In patients with recent acute coronary syndrome who did not undergo angioplasty, a single antiplatelet was added, and if post-angioplasty, dual antiplatelet therapy. LVT resolution was assessed after 3 months, and if residual thrombus was present, all anticoagulation was switched to warfarin after week 15.
  • In REWARF-STEMI, a 3-month, open-label, parallel-group RCT located in Iran, 26 patients were randomized to rivaroxaban 15 mg daily plus clopidogrel and aspirin and 24 to warfarin therapy with an INR goal of 2 to 2.5, plus clopidogrel and aspirin.15
  • In NO-LVT, a 6-month, open-label, multicenter RCT, rivaroxaban 20 mg daily was administered to 39 patients, and 40 to warfarin; over half of patients were also receiving dual-antiplatelet therapy.19 LVT resolution was assessed using transthoracic echocardiography (TTE) at 1, 3, and 6 months.

Across the RCTs included in the MA, 51 patients total were assigned to apixaban, 65 to rivaroxaban, and 112 to warfarin.15-19 The main efficacy outcome was 3-month complete LVT resolution, and the main safety outcome was 3-month major bleeding.15 The MA found that complete LVT resolution occurred in 93 out of 115 patients (80.8%) in the DOAC-based group, and in 79 out of 112 (70.5%) patients in the warfarin group at 3 months (risk ratio [RR] 1.14, 95% confidence interval [CI]: 0.98 to 1.32; p=0.08). For the safety assessment at 3 months, major bleeding occurred in 2/116 (1.7%) and 9/112 (8%) of patients in the DOAC and warfarin groups, respectively (risk difference, −0.06, 95% CI: −0.12 to 0.00; p=0.05). The risk of bias was considered low overall with some concerns for bias due to deviations from intended interventions. The study concluded that there were no significant differences between DOAC and warfarin in terms of complete LVT resolution or major bleeding events, suggesting that DOACs are at least as effective and as safe as warfarin for the treatment of LVT at 3 months.

Conclusion
Current guidance suggest DOACs are a reasonable alternative to warfarin for patients with LVT, although available direct comparative trials assessing apixaban versus warfarin are small in sample size and limited to patients experiencing LVT after STEMI. For the treatment of LVT, the RCTs employed an apixaban dose of 5 mg twice daily for at least 3 months, unless dose reductions were warranted due to age, renal function, or patient weight. Some studies reported extending anticoagulation (with apixaban or switched to warfarin) if there was residual thrombus after 3 months of anticoagulation. In most studies, antiplatelet therapy was also given. No RCTs have directly compared apixaban to warfarin for treatment of LVT in the setting of stroke or TIA, or in patients with DCM. Potential advantages with apixaban versus warfarin include fewer dietary restrictions, no INR monitoring, and fewer drug interactions.

References

  1. Levine GN, McEvoy JW, Fang JC, et al. Management of patients at risk for and with left ventricular thrombus: A scientific statement from the American Heart Association. Circulation. 2022;146(15):e205-e223. doi:10.1161/CIR.0000000000001092
  2. Habash F, Vallurupalli S. Challenges in management of left ventricular thrombus. Ther Adv Cardiovasc Dis. 2017;11(8):203-213. doi:10.1177/1753944717711139
  3. Stokman PJ, Nandra CS, Asinger RW. Left ventricular thrombus. Curr Treat Options Cardiovasc Med. 2001;3(6):515-521. doi:10.1007/s11936-001-0025-6
  4. Lattuca B, Bouziri N, Kerneis M, et al. Antithrombotic therapy for patients with left ventricular mural thrombus. J Am Coll Cardiol. 2020;75(14):1676-1685. doi:10.1016/j.jacc.2020.01.057
  5. Rao SV, O’Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the management of patients with acute coronary syndromes: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. Published online February 27, 2025. doi:10.1161/CIR.0000000000001309
  6. Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: A guideline from the American Heart Association/American Stroke Association. Stroke. 2021;52(7):e364-e467. doi:10.1161/STR.0000000000000375
  7. Eliquis [Package insert]. Princeton, NJ: Bristol-Myers Squibb; 2021.
  8. Heyne S, Macherey-Meyer S, Meertens MM, et al. Oral anticoagulation in patients with left ventricular thrombus: a systematic review and network meta-analysis with reconstructed time-to-event data. Clin Res Cardiol. Published online September 16, 2024. doi:10.1007/s00392-024-02547-7
  9. Vorla M, Kalra DK. Meta-Analysis of the safety and efficacy of direct oral anticoagulants for the treatment of left ventricular thrombus. Pharmaceuticals (Basel). 2024;17(6):708. Published 2024 May 30. doi:10.3390/ph17060708
  10. Haller PM, Kazem N, Agewall S, et al. Oral anticoagulation in patients with left ventricular thrombus: a systematic review and meta-analysis. Eur Heart J Cardiovasc Pharmacother. 2024;10(5):444-453. doi:10.1093/ehjcvp/pvae042
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  12. Hu T, Chen C, Maduray K, et al. Comparative effectiveness and safety of DOACs vs. VKAs in treatment of left ventricular thrombus- a meta-analysis update. Thromb J. 2024;22(1):23. Published 2024 Mar 1. doi:10.1186/s12959-024005859
  13. Shrestha DB, Dawadi S, Dhakal B, et al. Direct oral anticoagulants (DOAC) versus vitamin K antagonist in left ventricular thrombus: An updated meta-analysis. Health Sci Rep. 2023;6(11):e1736. Published 2023 Nov 24. doi:10.1002/hsr2.1736
  14. Kwok CS, Bennett S, Borovac JA, et al An evidence-based evaluation of left ventricular thrombus treatment, outcomes, and resolution: a systematic review, pooled analysis and meta-analysis. Coron Artery Dis. 2023;34(4):260-273. doi:10.1097/MCA.0000000000001230
  15. Jenab Y, Sadeghipour P, Mohseni-Badalabadi R, et al. Direct oral anticoagulants or warfarin in patients with left ventricular thrombus after ST-elevation myocardial infarction: a pilot trial and a prespecified meta-analysis of randomised trials. EuroIntervention. 2025;21(1):82-92. doi:10.4244/EIJ-D-24-00527
  16. Alcalai R, Butnaru A, Moravsky G, et al. Apixaban vs. warfarin in patients with left ventricular thrombus: a prospective multicentre randomized clinical trial. Eur Heart J Cardiovasc Pharmacother. 2022;8(7):660-667. doi:10.1093/ehjcvp/pvab057
  17. Youssef AA, Alrefae MA, Khalil HH, et al. Apixaban in Patients with post-myocardial infarction left ventricular thrombus: A randomized clinical trial. CJC Open. 2022;5(3):191-199. Published 2022 Dec 10. doi:10.1016/j.cjco.2022.12.003
  18. Isa WYHW, Hwong N, Mohamed Yusof AK, et al. Apixaban versus warfarin in patients with left ventricular thrombus: A pilot prospective randomized outcome blinded study investigating size reduction or resolution of left ventricular thrombus. Journal of Clinical and Preventive Cardiology. 2020;9:150-4. doi:10.4103/JCPC.JCPC_41_20
  19. Abdelnabi M, Saleh Y, Fareed A, et al. Comparative study of oral anticoagulation in left ventricular thrombi (No-LVT Trial). J Am Coll Cardiol. 2021;77(12):1590-1592. doi:10.1016/j.jacc.2021.01.049

Prepared by:
Dianne Verroya
PharmD Candidate Class of 2025
University of Illinois at Chicago Retzky College of Pharmacy

Reviewed and Edited by:
Christie Denton, PharmD, BCPS
Clinical Assistant Professor
University of Illinois at Chicago Retzky College of Pharmacy

May 2025

The information presented is current as of February 25, 2025. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.