Apixaban Versus Warfarin for Left Ventricular Thrombus (APEX)

Apixaban vs. Warfarin in Left Ventricular Thrombus: A Randomized, Noninferiority Trial

Left ventricular thrombus is a blood clot that forms in the left ventricle and is associated with risk of systemic embolism and ischemic stroke. Warfarin has historically been used for anticoagulation in this condition, but it requires frequent international normalized ratio monitoring and is affected by dietary and drug interactions. Apixaban is a direct oral factor Xa inhibitor with fixed dosing and no routine anticoagulation monitoring requirement, and it is increasingly used in clinical practice for left ventricular thrombus, although definitive randomized evidence remains limited.

This randomized, noninferiority trial will compare apixaban with warfarin for treatment of left ventricular thrombus. Eligible adults with recently confirmed left ventricular thrombus will be randomized 1:1 to apixaban or warfarin. The primary endpoint is complete left ventricular thrombus resolution at 3 months assessed by cardiac magnetic resonance imaging. Participants will be followed through 12 months for thrombus-related, bleeding, cardiovascular, and mortality outcomes.

Study Overview

• Status: Recruiting
• Conditions: Left Ventricular Thrombus
• Intervention / Treatment: Drug: Apixaban; Drug: Warfarin

• Study Type: Interventional
• Enrollment (Estimated): 218
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tushar Acharya, MD, MPH; Phone Number: 520-626-0968; Email: tacharya@arizona.edu

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Recruiting
      • Banner University Medical Center - Tucson
      • Principal Investigator: Tushar Acharya, MD, MPH
      • Principal Investigator: Song Peng Ang, MD
      • Principal Investigator: Alane Blythe C Dy, PhD, MSPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• LV thrombus confirmed within 14 days prior to randomization by CMR or contrast TTE or cardiac CT; baseline CMR required pre-randomization (or ≤7 days post-randomization if clinically unavoidable)
• Candidate for oral anticoagulation for ≥3 months
• Able to provide informed consent.

Exclusion Criteria:

• Absolute indication for VKA (mechanical valve, moderate-severe rheumatic MS and antiphospholipid syndrome) or clear preference or contraindication for one of the study drugs precluding randomization (see below)
• Antiphospholipid syndrome
• Estimated CrCl <15 mL/min or dialysis
• Severe hepatic impairment (ICD-10: K70.40, K70.41, K71.10, K71.11, K72.00, K72.01, K72.10, K72.11, K72.90, K72.91)
• Active clinically significant bleeding
• Platelets <50,000/µL
• Pregnancy or lactation; women of childbearing potential unwilling to use contraception
• Life expectancy <1 year or other conditions compromising follow-up

Additional contraindications to use of warfarin or apixaban. This includes, but is not limited to:

• Active pathological bleeding, major bleeding diathesis, or known blood dyscrasia
• Recent or planned surgery involving the central nervous system or eye, traumatic surgery with large open surfaces, or procedures (spinal/epidural puncture or major regional block anesthesia) where bleeding cannot be safely controlled.
• Conditions associated with high risk of bleeding such as threatened abortion, eclampsia, severe preeclampsia, or malignant/uncontrolled hypertension.
• History of severe hypersensitivity or allergy to warfarin or apixaban.
• Ongoing treatment with a combined P-gp and strong CYP3A4 inhibitor or inducer that cannot be safely discontinued or substituted. Examples include strong combined inhibitors such as ketoconazole, itraconazole, ritonavir or posiconazole, and strong combined inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apixaban; Participants randomized to apixaban will receive oral apixaban for treatment of left ventricular thrombus according to standard clinical dosing and follow-up.	Drug: Apixaban; Apixaban 5 mg orally twice daily
Active Comparator: Warfarin; Participants randomized to warfarin will receive oral dose-adjusted warfarin for treatment of left ventricular thrombus according to standard clinical care.	Drug: Warfarin; Warfarin will be prescribed with dose adjustment to maintain INR 2.0-3.0.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Left Ventricular Thrombus Resolution at 3 Months	Proportion of participants with complete resolution of left ventricular thrombus at 3 months, assessed by cardiac magnetic resonance imaging. The primary noninferiority comparison will use the absolute between-group difference in the proportion of participants with complete thrombus resolution, apixaban minus warfarin.	3 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Bleeding	Proportion of participants with major bleeding defined as BARC type 3 or 5 bleeding.	6 months
Change in LV Thrombus Volume	Change in thrombus volume assessed by CMR	Baseline to 3, 6, or 12 months
Left Ventricular Remodeling	Change in left ventricular ejection fraction and left ventricular volumes on follow-up imaging.	Baseline to 3, 6,12 months
Recurrent LV Thrombus	Proportion of participants with recurrent LV thrombus after documented resolution.	12 months
Ischemic Stroke	Proportion of participants with ischemic stroke.	12 months
Systemic embolism	Proportion of participants with systemic embolism	12 months
Cardiovascular Mortality	Proportion of participants with cardiovascular death.	12 months
All-Cause Mortality	Proportion of participants with death from any cause.	12 months

Collaborators and Investigators

• Sponsor: University of Arizona

Study record dates

Study Major Dates

• Study Start (Estimated): June 22, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: July 9, 2026
• First Submitted That Met QC Criteria: July 9, 2026
• First Posted (Actual): July 17, 2026

Study Record Updates

• Last Update Posted (Actual): July 17, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Stroke; Systemic Embolism; Intracardiac Thrombus; Cardiac Thrombus
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrans; Coumarins; Benzopyrans; 4-Hydroxycoumarins; Warfarin; apixaban
• Other Study ID Numbers: STUDY00007421

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No