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.

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.