Summary

• XARELTO is not indicated for the treatment of ventricular thrombus.¹
• In a randomized, controlled, open-label, non-inferiority study that evaluated the efficacy and safety of XARELTO in the management of left ventricular thrombus (LVT) in patients with acute coronary syndrome (ACS), thrombus resolution occurred in 76.9% of patients in the XARELTO group vs 69.2% of patients in the warfarin group; this difference was not statistically significant (P=0.53). Bleeding events occurred in 3.8% of patients in each group (P=1.000). The mean thrombus size change was significantly higher in the warfarin group (-228.23±168.95) than in the XARELTO group (-133.11±155.62).²
• In the R-DISSOLVE (an exploratory study of effectIveneSs and Safety of rivarOxaban in patients with Left VEntricular thrombus) trial, at week 12, thrombus resolution occurred in 50 (78.1%; 95% confidence interval [CI] 66.0-87.5) patients and major bleeding occurred in 2 (2.7%) patients.³
• In the No-LVT trial, complete LVT resolution occurred in 28 (71.8%), 30 (76.9%), and 34 (87.2%) patients in the XARELTO group, and 19 (47.5%), 27 (67.5%), and 32 (80%) patients in the warfarin group at 1, 3 and 6 months (P=0.03, 0.35, and 0.39 respectively).⁴
  • Major bleeding occurred in 2 patients (5.1%) in the XARELTO group and 6 patients (15%) in the warfarin group (P=0.11).
• Prospective and retrospective cohort studies and several case reports are available in the literature.^5-16
• Additional citations identified during a literature search are included in the REFERENCES section for your review.^17-25

Clinical Data

Mansouri et al (2024)² conducted a randomized, controlled, interventional, open-label, non-inferiority study that evaluated the efficacy and safety of XARELTO in the management of LVT in patients with ACS.

• The primary outcome was thrombus resolution, as assessed by transthoracic echocardiography (TTE) after a 3-month treatment follow-up.
• A total of 52 patients were included in the intention-to-treat analysis and were randomized to receive either XARELTO (n=26; mean age, 57.92 years; 88.5% were male) or warfarin (n=26; mean age, 55.08 years; 80.8% were male).
• The overall rate of LVT resolution was 73.1%. The LVT resolution rate was 76.9% in the XARELTO group vs 69.2% in the warfarin group; this difference was not statistically significant (P=0.53).
• Bleeding events occurred in 3.8% of patients in each group (P=1.000). Rehospitalization occurred in 3.8% of patients in the XARELTO group vs 7.7% of patients in the warfarin group (P=0.552). None of the groups had embolic events, stroke events, or MACEs.
• Both groups showed a significant improvement in thrombus size (P<0.05). The mean thrombus size change was significantly higher in the warfarin group (-228.23±168.95) than in the XARELTO group (-133.11±155.62).

R-DISSOLVE

R-DISSOLVE was a prospective, interventional, single-arm, open-label trial in adult patients (≥18 years old) with LVT confirmed by TTE, computed tomography, or cardiac magnetic resonance within 3 months and prior systemic oral shortterm anticoagulation treatment for less than 1 month. All patients were switched to XARELTO. This study was conducted at Fuwai Hospital (Beijing, China) between October 2020 and June 2022.³

• The median time to resolved thrombus was 45 (range 42-51) days, and the median time to unresolved thrombus was 84 (range 82-87) days. See Table: Efficacy Outcomes at Weeks 12 and 6.

• For safety outcomes, see Table: Safety Outcomes at Week 12.

No-LVT

No-LVT was a prospective, open-label, multi-center, randomized controlled trial in patients with recently diagnosed LVT. Patients were randomly assigned to receive either dose-adjusted warfarin or XARELTO 20 mg once daily. This study was conducted at 5 centers in Egypt and Bulgaria.⁴

• The primary efficacy outcome was complete LVT resolution, as assessed by TTE at 1, 3, and 6 months. Secondary efficacy outcomes included the incidence of stroke, systemic embolism, and a composite of both. The main safety outcome was the occurrence of major bleeding as defined by International Society on Thrombosis and Haemostasis criteria.
• It was estimated that 39 patients per group were needed in order to achieve an 80% power to demonstrate noninferiority. A total of 79 patients were randomized to receive either warfarin (n=40) or XARELTO (n=39). Baseline characteristics were balanced between the two groups.
• Complete LVT resolution occurred in 28 (71.8%), 30 (76.9%), and 34 (87.2%) patients in the XARELTO group, and 19 (47.5%), 27 (67.5%), and 32 (80%) patients in the warfarin group at 1, 3 and 6 months (P=0.03, 0.35, and 0.39 respectively).
• No strokes occurred in the XARELTO group, vs 4 patients (10%) in the warfarin group (P=0.08). No systemic embolisms occurred in the XARELTO group vs 2 events (5%) in the warfarin group (P=0.25). The composite of stroke and systemic embolism did not occur in the XARELTO group and occurred for 6 patients (15%) in the warfarin group (P=0.01).
• Major bleeding occurred in 2 patients (5.1%) in the XARELTO group and 6 patients (15%) in the warfarin group (P=0.11).

Prospective and Retrospective Cohort Studies

Saeed et al (2023)¹⁶ conducted a prospective cohort study to compare the outcomes and safety of XARELTO vs warfarin in patients with newly diagnosed LVT between July 1, 2022, and December 1, 2022. A total of 196 patients (40-80 years old) were included. In patients receiving XARELTO 20 mg daily (n=98) vs warfarin (n=98), the complete thrombus resolution occurred in 73 (74.49%) vs 76 (77.5%) patients (P=0.310); the partially thrombus resolution occurred in 19 (19.39%) vs 12 (12.24%) patients (P=0.085); and the thrombus unresolved occurred in 6 (6.12%) vs 10 (10.20%) patients (P=0.1484). In patients receiving XARELTO vs warfarin, the major bleeding (Bleeding Academic Research Consortium [BARC] type 4) occurred in 4 (4.08%) vs 5 (5.10%) patients (P=0.366); and the minor bleeding (BARC type 1-2) occurred in 14 (14.29%) vs 18 (18.37%) patients (P=0.2198).

Jones et al (2021)⁵ conducted a prospective, observational single center cohort study to assess the safety and efficacy of non-vitamin K antagonist oral anticoagulants (NOACs; apixaban, edoxaban, XARELTO) compared to a vitamin K antagonist (VKA; warfarin) as treatment for LVT in patients presenting with acute myocardial infarction undergoing primary percutaneous coronary intervention between May 2015 to December 2018. A total of 101 patients diagnosed with LVT were included in this study. Sixty patients (59.4%) were started on warfarin and 41 patients (40.6%) were treated with NOAC therapy (XARELTO: 58.5%, apixaban: 36.5%, edoxaban: 5%). Median time to first imaging was 175 days (interquartile range 98-340) and 151 (63-352) for the VKA group and NOAC group respectively (P=0.414). A total of 29 patients (48.3%) in the VKA group and 29 patients (70.7%) in the NOAC group had thrombus resolution on their first follow-up imaging (P=0.04). Over the follow-up period (median 2.2 years) there was greater and earlier LVT resolution in the NOAC group (82%) compared to patients who took warfarin (64.4%) at 1 year (P=0.0018), which persisted after adjusting for baseline variables (odds ratio [OR] 1.8, 95% CI 1.2-2.9). Thrombus resolution rates were 88% for XARELTO, 93% for apixaban, and 100% for edoxaban. There was no difference in the rate of systemic thromboembolism seen between the two treatment groups (NOAC 2.4% vs VKA 5%, P=0.388) over the follow-up period. The incidence of major bleeding events in the VKA group was 6.7% compared to 0% in the NOAC group (P=0.03).

Iqbal et al (2021)⁶ conducted a retrospective, observational cohort study to assess the characteristics and outcomes of patients with LVT treated with either VKA or direct oral anticoagulants (DOACs) between December 2012 and June 2018. During the study period, 84 patients were diagnosed with and managed for LVT. A total of 62 patients (74%) received warfarin at variable dosage and 22 (26%) received a DOAC (13 were prescribed XARELTO 20 mg once daily, 8 prescribed apixaban 5 mg twice daily, and 1 dabigatran 150 mg twice daily). During an average follow-up of 3.0±1.4 years, there were no statistically significant differences between VKA and DOAC in rates of stroke (2% vs 0%, P=0.55), other thromboemboli (2% vs 0%, P=0.55), or clinically significant bleeding (10% vs 0%, P=0.13). The mean duration between diagnosis and repeat imaging was 233±251 days with no difference between groups (P=0.83). There was no difference in the rate of resolution of thrombus in 55 (73%) patients who underwent repeat imaging, 42 of whom receiving VKA and 13 received DOAC (rate 76% vs 65%, P=0.33). Rehospitalization (50% vs 45%: P=0.53) and all-cause mortality (10% vs 14%; P=0.61) were also similar.

Bahmaid et al (2019)⁷ conducted a retrospective cohort study to assess the efficacy of DOAC, dabigatran or XARELTO, on the resolution of LVT. During the study period, December 2011 to December 2016, 299 on dabigatran and 448 on XARELTO were identified. After an echocardiogram, 11 patients were diagnosed with LVT. Seven of the patients were started on DOACs from the start and 4 were started on warfarin and then switched to a DOAC. Dosages given were 20 mg/day and 15 mg/day XARELTO in 3 patients each and dabigatran 100 mg twice daily in 1 patient. Comorbidities included ACS, atrial fibrillation, and heart failure. All patients were male, mean ages 49±18.3 years, and duration of therapy ranged from 2 months to 28 months. All 7 patients on a DOAC start showed LVT resolution.

CASE REPORTS

Al-Maqbali et al (2021)⁸ reported a 43-year-old man with human immunodeficiency virus (HIV) infection, HIV-associated dilated cardiomyopathy (left ventricular ejection fraction [LVEF] <20%), atrial flutter, and chronic limb ischemia. He was treated with XARELTO 20 mg once daily for 9 consecutive months with no interruption of therapy. He presented to the emergency department with symptoms of decompensated heart failure. A follow-up two-dimensional TTE demonstrated an increase in the size of LVT from 10x35 mm to 27x60 mm in diameter in the apical three 26x33 mm in the apical four-chamber view. Due to the progression of LVT, XARELTO was switched back to warfarin. There was an adequate clinical response with warfarin, evidenced by reducing LVT size on the first follow-up TTE 4 months after initiating warfarin.

DeCampos et al (2020)⁹ reported a 61 year-old male who presented to the emergency department with a history of dyslipidemia, hypertension, and intense chest pain 8 hours prior. On the left ventricular (LV) wall an apical thrombus was seen on a transthoracic echocardiograph and the patient was started on XARELTO 20 mg a day (after meals) in addition to aspirin 100 mg/day and clopidogrel 75 mg/day. Patient was discharged on dual-antithrombotic therapy (clopidogrel 75 mg/day and XARELTO 20 mg) and guideline directed management of coronary artery disease and heart failure. A follow up visit 1 month later showed no visible thrombus with no improvement in LVEF and wall motion abnormalities. Between initial and follow-up visits, no evidence of clinical thromboembolic events was noted.

Abdelnaby et al (2019)¹⁰ described 8 case reports utilizing XARELTO instead of warfarin for LVT. A dose of 15 mg/day (5 cases) and 20 mg/day (3 cases) were given along with aspirin 100 mg/day and clopidogrel 75 mg/day (dual antiplatelet therapy [DAPT]). Follow-up at 3 months showed the presence of thrombus in 1 patient (15 mg/day dose) and no bleeding of any type, stroke, or distal embolization in all patients.

Sun et al (2018)¹¹ reported a 43-year-old Asian male who presented with dizziness at rest and was diagnosed with a LVT and LV non-compaction cardiomyopathy. The ejection fraction was reduced to 43. He was started on XARELTO 10 mg once daily. The thrombus resolved after 3 months treatment with XARELTO. After thrombus resolution, follow-up exams confirmed LV non-compaction cardiomyopathy and non-sustained ventricular tachycardia. Thus, he continued XARELTO 10 mg daily to prevent future thrombosis.

Abubakar et al (2018)¹² described a case of a 28-year-old female with phocomelia and nonischemic cardiomyopathy who developed shortness of breath and was diagnosed with acute decompensated heart failure (ejection fraction 15%) along with a LV postero-apical thrombus. Due to congenital limb abnormality and limited peripheral venous access, warfarin was deemed an unsuitable anticoagulant. The patient was discharged on apixaban 5 mg twice daily and transthoracic echocardiograms 6 and 11 months later found the LVT still present but reduced in size. The patient admitted noncompliance with the twice daily apixaban regimen, so she was switched to XARELTO once daily and a few months later the LVT resolved. There were no bleeding complications during the follow-up period.

Huang et al (2018)¹³ reported a case of a 65-year-old male with dyspnea and bilateral lower extremity edema upon visit to the outpatient department. Akinesia of the anterior wall and apex with a thrombus over the LV apex was revealed by echocardiogram. Patient was prescribed warfarin for 3 months and maintained at an optimal therapeutic range (international normalized ratio [INR] between 2.0 and 3.0). XARELTO 15 mg/day replaced warfarin after a transthoracic echocardiogram showed no significant reduction in LVT. An echocardiogram, 1 month later, showed the thrombus had dissolved completely. At an outpatient follow up, 6 months later, the patient was symptom free with no other complications (ie, gastrointestinal bleeding).

Bhatnagar et al (2018)¹⁴ described a case of a 64-year-old male who presented with respiratory distress and hypotension in the emergency department. An LVT was confirmed by echocardiogram. Treatment was started, intravenous heparin infusion and cardiogenic shock followed by stenting with a drug eluting sent. Warfarin was initiated for LVT and bilateral pulmonary embolism, also on DAPT (aspirin/clopidogrel) post coronary intervention. About 1 month post ST-segment elevation myocardial infarction (STEMI), echocardiogram was repeated, and patient continued to show a large LVT. Warfarin was changed to XARELTO due to sub-therapeutic INR since initial discharge. Patient showed no signs of LVT 7 months after the sentinel event.

Lypovetska et al (2018)¹⁵ reported a case of a 53-year-old male who presented with an anterior STEMI. The patient had recurrence of new chest pain on day 9 of stay and coronary intervention was refused. Apical dyskinesis with thrombus was identified and patient received aspirin 100 mg and clopidogrel 75 mg (DAPT) and enoxaparin for 7 days before being switched to XARELTO 15 mg/day. Complete dissolution of the apical thrombus was revealed in 6 weeks and to prevent a major bleeding event patient continued DAPT without XARELTO.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 30 October 2024.