Early pharmacologic venous thromboembolism prophylaxis and in-hospital mortality in ICU patients with intracerebral hemorrhage: a landmark, propensity-weighted cohort study.

Overview

1. Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
2. Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
3. Department of Neurosurgery, Liaocheng People’s Hospital, Liaocheng, Shandong, China

Abstract

Background and purpose: The optimal timing of pharmacologic venous thromboembolism (VTE) prophylaxis in intracerebral hemorrhage (ICH) is uncertain. Using a landmark design that classifies exposure only by information available at a fixed time point, we evaluated whether initiation of pharmacologic VTE prophylaxis within 48 h of ICU admission is associated with in-hospital mortality.

Methods: Retrospective cohort study in the Medical Information Mart for Intensive Care IV (MIMIC-IV v3.1). Adults with non-traumatic ICH admitted to the ICU (2008–2019) who were alive and in hospital at a 48-h landmark were included. Exposure was fixed at the landmark: early prophylaxis = pharmacologic prophylaxis started ≤48 h; no early prophylaxis = not started by 48 h (comprising later [delayed] initiators and never-treated patients). Time zero and eligibility were ICU admission + 48 h. Inverse probability of treatment weighting (IPTW) adjusted for 17 baseline covariates including the baseline Glasgow Coma Scale (GCS). The primary outcome was in-hospital mortality (a binary outcome, with discharge alive as the competing event); the secondary outcome was coded VTE (binary). Missing GCS was handled by multiple imputation.

Results: Of 2,754 ICH ICU patients, 2,407 reached the 48-h landmark and 2,380 formed the analytic cohort (early prophylaxis, n = 655; no early prophylaxis, n = 1,725) after excluding 27 receiving therapeutic anticoagulation within 48 h. In-hospital death occurred in 371 patients (early prophylaxis 10.8%, no early prophylaxis 17.4%). After IPTW (17/17 covariates standardized mean difference <0.1), early prophylaxis was associated with lower in-hospital mortality (adjusted odds ratio [OR] 0.72, 95% confidence interval [CI] 0.55–0.94; weighted risk difference −4.0%; cause-specific hazard ratio 0.65, 95% CI 0.50–0.86, p = 0.003). There was no statistically significant difference in coded VTE (adjusted OR 1.20, 95% CI 0.85–1.69; p = 0.31). The association was directionally consistent across most sensitivity analyses—including a model that treated prophylaxis initiation as a time-varying exposure to reduce immortal-time bias (HR 0.61, 95% CI 0.49–0.76) and a competing-risk cumulative-incidence analysis—although the 24-h landmark estimate was not statistically significant.

Conclusion: In this landmark cohort, initiation of pharmacologic VTE prophylaxis within 48 h was associated with lower in-hospital mortality without a statistically significant difference in coded VTE. Because key neuroimaging severity measures (hematoma volume, location, intraventricular extension, and expansion) were unavailable, residual confounding by indication cannot be excluded and a causal interpretation is not warranted. Randomized trials are needed.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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Data availability statement

Publicly available datasets were analyzed in this study. The data are available from the Medical Information Mart for Intensive Care IV (MIMIC-IV v3.1) database at https://physionet.org/content/mimiciv/3.1/. Access to MIMIC-IV requires completion of a data use agreement and human subjects research training (CITI Program). The analysis code is available from the corresponding authors upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Recorded: type, language, journal, volume, pages, dates, 5 authors, 6 keywords, 14 MeSH terms, 27 references.

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This paper

Chen, H., Ji, J., Zhang, H., Nie, E., & Lan, Q. (2026). Early pharmacologic venous thromboembolism prophylaxis and in-hospital mortality in ICU patients with intracerebral hemorrhage: a landmark, propensity-weighted cohort study. Frontiers in neurology, 17, 1849021. https://doi.org/10.3389/fneur.2026.1849021

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