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Meta-Analysis
. 2025 Jan 6;21(1):82-92.
doi: 10.4244/EIJ-D-24-00527.

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

Yaser Jenab  1 , Parham Sadeghipour  2   3 , Reza Mohseni-Badalabadi  1 , Raheleh Kaviani  4 , Kaveh Hosseini  1 , Yeganeh Pasebani  2 , Hamid Khederlou  1 , Ali Rafati  2   5 , Zohre Mohammadi  1 , Sepehr Jamalkhani  2 , Azita Haj Hossein Talasaz  6   7   8 , Ata Firouzi  5 , Hamid Ariannejad  1 , Mohammad Javad Alemzadeh-Ansari  5 , Sajjad Ahmadi-Renani  1 , Mohsen Maadani  5 , Melody Farrashi  2   4 , Hooman Bakhshandeh  2   3 , Gregory Piazza  9   10 , Harlan M Krumholz  11   12 , Roxana Mehran  13 , Gregory Y H Lip  14   15 , Behnood Bikdeli  9   10   12
Affiliations
Meta-Analysis

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

Yaser Jenab et al. EuroIntervention. .

Abstract

Background: The role of direct oral anticoagulants (DOACs) in the treatment of left ventricular thrombus (LVT) after ST-elevation myocardial infarction (STEMI) remains uncertain.

Aims: We aimed to compare the effect of rivaroxaban versus warfarin in patients with STEMI complicated by LVT.

Methods: Adult patients with STEMI and two-dimensional transthoracic echocardiography showing LVT were assigned to rivaroxaban (15 mg once daily) or warfarin (international normalised ratio goal of 2.0-2.5) in an open-label, randomised clinical trial (RCT). A prospective pooled analysis was planned comparing DOAC- versus warfarin-based anticoagulation for the same indication. The main outcome of the RCT was complete LVT resolution at 3 months, determined by a blinded imaging core laboratory. Complete LVT resolution and bleeding were investigated in the pooled analysis.

Results: A total of 50 patients (median age: 55 years, 18% females) were enrolled from June 2020 to November 2022. Three-month complete LVT resolution occurred in 19/25 (76.0%) patients assigned to rivaroxaban and 13/24 (54.2%) assigned to warfarin (relative risk [RR] 1.40, 95% confidence interval [CI]: 0.91-2.15; p=0.12) with no thrombotic or major bleeding events. Pooled analysis showed numerically better complete LVT resolution with DOACs (rivaroxaban and apixaban; 93/115 [80.8%] vs 79/112 [70.5%], RR 1.14, 95% CI: 0.98-1.32; p=0.08) and less major bleeding (2/116 [1.7%] and 9/112 [8.0%], risk difference -0.06, 95% CI: -0.12 to 0.00; p=0.05) than with warfarin.

Conclusions: Although the findings are limited by a small sample size, the results suggest that DOACs are safe with at least similar outcomes concerning LVT resolution and major bleeding compared with warfarin. (ClinicalTrials.gov: NCT05705089).

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Conflict of interest statement

G. Piazza has received research grants (paid to his institution) from BMS/Pfizer, Janssen, Alexion, Bayer, Amgen, Boston Scientific, Esperion, and the NIH (1R01HL164717-01); and has received consulting fees for advisory roles from Boston Scientific, Amgen, PERC, NAMSA, BMS, Janssen, Penumbra, and Thrombolex. H.M. Krumholz received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, and F-Prime; he is a co-founder of Refactor Health and Hugo Health; and has contracts through Yale New Haven Hospital from the Centers for Medicare & Medicaid Services and through Yale University from Johnson & Johnson. G.Y.H. Lip is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Anthos, although no fees are received personally; and he is a National Institute for Health and Care Research (NIHR) senior investigator and co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 899871, outside the submitted work. B. Bikdeli is supported by a Career Development Award from the American Heart Association and VIVA Physicians (#938814); was supported by the Scott Schoen and Nancy Adams IGNITE Award; is supported by the Mary Ann Tynan Research Scientist award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, and the Heart and Vascular Center Junior Faculty Award from Brigham and Women’s Hospital; reports that he was a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of IVC filters but was not involved in the litigation in 2022-2024 nor did he receive any compensation in 2022-2024; he reports that he is a member of the Medical Advisory Board for the North American Thrombosis Forum; and serves on the Data Safety and Monitory Board of the NAIL-IT trial funded by the National Heart, Lung, and Blood Institute, and Translational Sciences. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Trial flow diagram.
2D: two-dimensional; APS: antiphospholipid syndrome; eGFR: estimated glomerular filtration rate; INR: international normalised ratio; LVT: left ventricular thrombus; STEMI: ST-elevation myocardial infarction; TTE: transthoracic echocardiography
Figure 2
Figure 2. Summary of the baseline characteristics and reported outcomes in randomised clinical trials included in the pooled analysis.
Note: In all studies, apixaban 5 mg was administered (except for Abdelnabi et al and REWARF-STEMI administering rivaroxaban 20 mg and 15 mg, respectively), and warfarin was adjusted to achieve an INR of 2-3. *MACE: a composite of death from cardiovascular causes, MI, or stroke. †Three trials (Alcalai et al, Abdelnabi et al, and REWARF-STEMI) and one trial (Youssef et al14) defined bleeding based on ISTH and BARC definitions, respectively, and one trial (Isa et al17) did not use a specific definition. ‡In the RCT by Alcalai et al, at 3 months, 17 and 15 patients were followed up in the DOAC and warfarin groups, respectively; in REWARF-STEMI, at 3 months, 25 and 24 patients were followed up in the DOAC and warfarin groups, respectively. 2D: two-dimensional; BARC: Bleeding Academic Research Consortium; CRNMB: clinically relevant non-major bleeding; D: direct; F/U: follow-up; INR: international normalised ratio; ISTH: International Society on Thrombosis and Haemostasis; LV: left ventricular; LVT: left ventricular thrombus; MACE: major adverse cardiac events; MI: myocardial infarction; NA: not available; OAC: oral anticoagulant; TTE: transthoracic echocardiography; W: warfarin
Figure 3
Figure 3. Pooled analysis of complete left ventricular thrombus resolution and major bleeding.
A) Complete LVT resolution in DOAC versus warfarin treatment groups. B) Major bleeding in DOAC and warfarin treatment groups. Note: The study by Isa et al was conducted on patients with LVT, out of whom only patients with post-AMI LVT were included in the meta-analysis, as confirmed by the corresponding author. Similarly, the study by Abdelnabi et al did not differentiate between post-AMI LVT and LVT due to other causes. However, they did not respond to our multiple inquiries. AMI: acute myocardial infarction; CI: confidence interval; DOAC: direct oral anticoagulant; ISTH: International Society on Thrombosis and Haemostasis; LVT: left ventricular thrombus; RD: risk difference; RR: relative risk
Central illustration
Central illustration. Summary of REWARF-STEMI trial results and published RCTs on the role of DOAC versus warfarin in patients with echocardiographically diagnosed LVT after STEMI.
No ISTH major bleeding event was registered in REWARF-STEMI. CI: confidence interval; DOAC: direct oral anticoagulant; ISTH: International Society on Thrombosis and Haemostasis; LVT: left ventricular thrombus; RCT: randomised clinical trial; RD: risk difference; REWARF-STEMI: Rivaroxaban vErsus Warfarin for Antithrombotic TheRapy in Patients with LeFt Ventricular Thrombus After Acute ST-Elevation Myocardial Infarction; RR: relative risk; SRMA: systematic review and meta-analysis; STEMI: ST-elevation myocardial infarction
See this image and copyright information in PMC

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