Withdrawal of aspirin in patients with left ventricular assist device treated with vitamin K antagonists: impact of anticoagulation quality in the randomized ARIES-HM3 trial
Recommended Citation
Connors JM, Gustafsson F, Uriel N, Pagani FD, Jorde UP, Katz JN, Netuka I, Zimpfer D, Nemeh H, Ransom JM, Agarwal R, Byku M, Givertz MM, Hall S, Kanwar MK, Cogswell R, Sheikh FH, Phancao A, Ravichandran A, Conway J, Adler E, Chung ES, Grinstein J, Dirckx N, Chakouri N, and Mehra MR. Withdrawal of aspirin in patients with left ventricular assist device treated with vitamin K antagonists: impact of anticoagulation quality in the randomized ARIES-HM3 trial. Eur Heart J 2025;47(8):942-952.
Document Type
Article
Publication Date
2-23-2026
Publication Title
European heart journal
Keywords
Humans, Heart-Assist Devices, Aspirin, Male, Female, Double-Blind Method, Middle Aged, Anticoagulants, Vitamin K, Hemorrhage, Aged, Heart Failure, Thrombosis, Withholding Treatment
Abstract
BACKGROUND AND AIMS: Left ventricular assist devices (LVADs), including the HeartMate 3 (HM3), have improved outcomes in patients with advanced heart failure. Use of vitamin K antagonists (VKA) is mandated to reduce the risk of thrombotic events, but there is heterogeneity in management. Time in therapeutic range (TTR) is a crucial metric for assessing the quality of VKA management. The ARIES-HM3 trial demonstrated that aspirin can be safely omitted from the antithrombotic regimen, resulting in reduced bleeding without increased thrombosis. This pre-specified trial analysis explores the relationship of quality of VKA management assessed by TTR with haemocompatibility-related outcomes.
METHODS: ARIES-HM3 was an international, randomized, double-blind, placebo-controlled study of aspirin (100 mg/day) or placebo (1:1) with VKA therapy in patients with de-novo HM3 placement. Participants were stratified into low TTR or high TTR groups based on median levels (n = 554). Primary endpoint success and secondary endpoint rates were stratified based on TTR groups. Bleeding rates at 12 months were estimated using an Andersen-Gill model with TTR as a single continuous variable, and multivariable regression analysis was performed.
RESULTS: The percentage of patients with a TTR above or below the median of 56 was similar between the aspirin and placebo groups. More participants achieved primary endpoint success with TTR ≥56% (77% vs 66.9%, P = .01). Higher TTR was associated with lower bleeding rates at 12 months (26.4 vs 49.2 events per 100 participant-years; rate ratio 1.84, 95% confidence interval [CI] 1.37-2.53) without stroke increase (3.2 vs 2.8 events per 100 participant-years; rate ratio 0.88 [95% CI: 0.30-2.53]). No interaction was observed between the assigned treatment group and TTR. Modelling demonstrated a constant decrease in bleeding as a function of increasing TTR. Female sex and Black race were independent predictors of low TTR (odds ratio: 1.70 [95% CI: 1.12-2.57]; 1.62 [95% CI: 1.11-2.35], respectively), with more frequent INRs below the therapeutic range. Multivariable modelling identified age ≥65 years, aspirin use, TTR < 56%, and blood urea nitrogen ≥30 mg/dL as predictors of non-surgical bleeding.
CONCLUSIONS: The quality of VKA management as measured by TTR correlates with the occurrence of non-surgical bleeding in patients with the HM3 LVAD, with a lower TTR associated with an increased bleeding risk. These data provide new clinical direction to define a benchmark TTR to achieve further mitigation of residual risk of bleeding and enhance haemocompatibility with the HM3 LVAD.
Medical Subject Headings
Humans; Heart-Assist Devices; Aspirin; Male; Female; Double-Blind Method; Middle Aged; Anticoagulants; Vitamin K; Hemorrhage; Aged; Heart Failure; Thrombosis; Withholding Treatment
PubMed ID
41206679
ePublication
ePub ahead of print
Volume
47
Issue
8
First Page
942
Last Page
952
