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DOAC LVAD

Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices

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Year of Publication: 2025

Authors: Aditya Mehta, Pramita Bagchi, Mary Looby, ..., Palak Shah

Journal: The Journal of Heart and Lung Transplantation

Citation: J Heart Lung Transplant 2025;44:1987–1991

Link: https://doi.org/10.1016/j.healun.2025.08.012

PDF: https://www.jhltonline.org/action/showPd...%2825%2902210-7

Clinical Question

Is long-term anticoagulation with apixaban feasible and safe compared to warfarin in patients with HeartMate 3 left ventricular assist devices?

Bottom Line

At 2 years, apixaban anticoagulation in LVAD patients was feasible with numerically fewer hemocompatibility-related adverse events compared to warfarin, though the small sample size limited statistical power. Significantly fewer blood transfusions were required with apixaban.

        Major Points
        Prospective phase 2 open-label randomized trial of 30 LVAD patients
Primary composite outcome (death or HRAE) occurred in 12.5% of apixaban vs 43% of warfarin patients (p=0.087)
HRAEs occurred in 6.3% apixaban (1 major bleed) vs 35.7% warfarin (1 hemorrhagic stroke, 3 major bleeds, 1 RV thrombus) (p=0.07)
All bleeding events were gastrointestinal in nature
Significantly lower RBC transfusion rates with apixaban (0.69 vs 4.82 EPPY, p<0.01)
Win ratio analysis using hierarchical composite favored apixaban (WR 2.30, 95% CI 0.95-5.60, p=0.066)
No dose adjustment of apixaban was used given 30% had comorbid VTE and 70% had atrial fibrillation

      

Design

Study Type: Prospective, phase 2, open-label, randomized trial

Randomization: 1

Blinding: Open-label (no blinding)

Enrollment Period: Started 2022

Follow-up Duration: 2 years

Centers: 1

Countries: USA

Sample Size: 30

Analysis: Kaplan-Meier curves with log-rank tests for survival analysis; win ratio for hierarchical composite endpoint; R version 4.2

Inclusion Criteria

Age ≥18 years
HeartMate 3 LVAD recipient
No history of post-LVAD stroke
No history of gastrointestinal bleeding post-LVAD
No history of device thrombosis

Exclusion Criteria

Not specified in detail in this publication (referenced to prior design paper)

Baseline Characteristics

Characteristic	Control	Active
N	14	16
Age - Median (Q1-Q3)	60 years (52-71) [overall cohort]	60 years (52-71) [overall cohort]
Nonischemic cardiomyopathy	70% [overall cohort]	70% [overall cohort]
Atrial fibrillation history	73% [overall cohort]	73% [overall cohort]
Venous thromboembolism history	30% [overall cohort]	30% [overall cohort]
Median time from LVAD to enrollment	115 days [overall cohort]	115 days [overall cohort]

Arms

Field	Apixaban	Control
Intervention	Apixaban 5 mg twice daily without dose adjustment, plus aspirin 81 mg daily initially (later discontinued after ARIES-HM3 and DOT-HM3 results)	Warfarin titrated to INR goal of 2.0-2.5, plus aspirin 81 mg daily initially (later discontinued after ARIES-HM3 and DOT-HM3 results)
Duration	2 years	2 years

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Survival free of hemocompatibility-related adverse events (HRAEs) including death, stroke, device thrombosis, major bleeding, aortic root thrombus, and/or arterial non-CNS thromboembolism at 2 years	Primary	6 patients (43%)	2 patients (12.5%)		0.087
HRAEs alone (excluding death)	Secondary	5 (35.7%)	1 (6.3%)		0.07
Death	Secondary	2 (14.3%)	1 (6.3%)	0.55 (0.05-6.13)	0.48
Hierarchical composite win ratio (death, HRAE, hospitalization, transfusion)	Secondary	28.1% wins	64.8% wins	Win ratio 2.30 (0.95-5.60)	0.066
All-cause hospitalization rate (EPPY)	Secondary	5.49	5.96	1.08 (0.69-1.72)	0.72
RBC transfusion rate (EPPY)	Secondary	4.82	0.69	0.05 (0.14-0.35)	<0.01
Stroke	Adverse	1 (0.16 EPPY)	0	0 (0-15.84)	0.99
Device thrombosis	Adverse	0	0
Major GI bleeding	Adverse	5 (0.83 EPPY)	1 (0.14 EPPY)	0.01 (0.19-1.20)	0.10
Aortic root thrombus	Adverse	0	0
Arterial non-CNS thromboembolism	Adverse	1 (0.16 EPPY)	0	0 (0-15.84)	1.00

Subgroup Analysis

Not formally reported. Five patients transitioned from apixaban to warfarin at higher priority transplant listing (median 400 days from randomization). Two patients bridged to transplant in warfarin arm. One patient in apixaban group underwent LVAD explantation for recovery at 141 days.

Criticisms

Small single-center trial (n=30) limiting generalizability and statistical power
Patients enrolled at median 115 days post-LVAD implantation, excluding high-risk early postoperative period
All patients initially received aspirin which was later discontinued, creating heterogeneity
Five patients transitioned from apixaban to warfarin for urgent transplant listing, potentially biasing results in favor of apixaban
Open-label design with potential for bias
Results are exploratory and require confirmation in larger trials

Funding

Not explicitly stated; protocol received input from the Food and Drug Administration and independent data safety monitoring board

Based on: DOAC LVAD (The Journal of Heart and Lung Transplantation, 2025)

Authors: Aditya Mehta, Pramita Bagchi, Mary Looby, ..., Palak Shah

Citation: J Heart Lung Transplant 2025;44:1987–1991

Content summarized and formatted by NeuroTrials.ai.

DOAC LVAD

(2025)

Objective

To evaluate the long-term feasibility and safety of apixaban anticoagulation compared to warfarin in patients with HeartMate 3 left ventricular assist devices

Study Summary

• Apixaban demonstrated numerically fewer HRAEs (stroke, bleeding or thrombosis) than warfarin (12.5% vs 43%, p=0.087)
• Significantly lower transfusion requirements with apixaban (0.69 vs 4.82 EPPY, p<0.01)
• Win ratio analysis favored apixaban (2.30, 95% CI 0.95-5.60)

Intervention

Apixaban 5 mg twice daily without dose adjustment vs warfarin (INR goal 2.0-2.5), both with initial aspirin 81 mg daily (later discontinued)

Inclusion Criteria

Age ≥18 years, HeartMate 3 LVAD recipients, no history of post-LVAD stroke, gastrointestinal bleeding, or device thrombosis

Study Design

Arms: Apixaban 5 mg BID vs Warfarin (INR 2.0-2.5)

Patients per Arm: Apixaban: 16, Warfarin: 14

Outcome

• Primary composite (death or HRAE): 12.5% apixaban vs 43% warfarin (p=0.087)
• HRAEs alone: 6.3% apixaban vs 35.7% warfarin (p=0.07)
• Death: 6.3% apixaban vs 14.3% warfarin (p=0.48)

Bottom Line

Major Points

Prospective phase 2 open-label randomized trial of 30 LVAD patients
Primary composite outcome (death or HRAE) occurred in 12.5% of apixaban vs 43% of warfarin patients (p=0.087)
HRAEs occurred in 6.3% apixaban (1 major bleed) vs 35.7% warfarin (1 hemorrhagic stroke, 3 major bleeds, 1 RV thrombus) (p=0.07)
All bleeding events were gastrointestinal in nature
Significantly lower RBC transfusion rates with apixaban (0.69 vs 4.82 EPPY, p<0.01)
Win ratio analysis using hierarchical composite favored apixaban (WR 2.30, 95% CI 0.95-5.60, p=0.066)
No dose adjustment of apixaban was used given 30% had comorbid VTE and 70% had atrial fibrillation

Study Design

Study Type: Prospective, phase 2, open-label, randomized trial
Randomization: Yes
Blinding: Open-label (no blinding)
Sample Size: 30
Follow-up: 2 years
Centers: 1
Countries: USA

Primary Outcome

Definition: Survival free of hemocompatibility-related adverse events (HRAEs) including death, stroke, device thrombosis, major bleeding, aortic root thrombus, and/or arterial non-CNS thromboembolism at 2 years

Control	Intervention	HR/OR	P-value
6 patients (43%)	2 patients (12.5%)	-	0.087

Limitations & Criticisms

Small single-center trial (n=30) limiting generalizability and statistical power
Patients enrolled at median 115 days post-LVAD implantation, excluding high-risk early postoperative period
All patients initially received aspirin which was later discontinued, creating heterogeneity
Five patients transitioned from apixaban to warfarin for urgent transplant listing, potentially biasing results in favor of apixaban
Open-label design with potential for bias
Results are exploratory and require confirmation in larger trials

Citation

J Heart Lung Transplant 2025;44:1987–1991

View Original Publication →

DOAC LVAD

Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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