Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis.

Kuramatsu J, Gerner S, Ziai W, Bardutzky J, Sembill J, Sprügel M, Mrochen A, Kölbl K, Ram M, Avadhani R, Falcone GJ, Selim MH, Lioutas VA, Endres M, Zweynert S, Vajkoczy P, Ringleb PA, Purrucker JC, Volkmann J, Neugebauer H, Erbguth F, Schellinger PD, Knappe UJ, Fink GR, Dohmen C, Minnerup J, Reichmann H, Schneider H, Roether J, Reimann G, Schwarz M, Baezner H, Classen J, Michalski D, Witte OW, Guenther A, Hamann GF, Lücking H, Dörfler A, Ishfaq MF, Chang JJ, Testai FD, Woo D, Alexandrov A, Staykov D, Goyal N, Tsivgoulis G, Sheth KN, Awad IA, Schwab S, Hanley DF, Huttner H (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 53

Pages Range: 2876-2886

Journal Issue: 9

DOI: 10.1161/STROKEAHA.121.038455

Abstract

BACKGROUND: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. METHODS: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). RESULTS: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome. CONCLUSIONS: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials.

Authors with CRIS profile

Involved external institutions

Johns Hopkins University (JHU) United States (USA) (US) Albert-Ludwigs-Universität Freiburg Germany (DE) Yale University United States (USA) (US) Harvard University United States (USA) (US) Charité - Universitätsmedizin Berlin Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Julius-Maximilians-Universität Würzburg Germany (DE) Klinikum Nürnberg Germany (DE) Johannes Wesling Klinikum Minden Germany (DE) Universität zu Köln Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) Technische Universität Dresden Germany (DE) Asklepios Klinik Altona Germany (DE) Klinikum Dortmund Germany (DE) Klinikum Stuttgart Germany (DE) Universität Leipzig Germany (DE) Friedrich-Schiller-Universität Jena Germany (DE) Bezirkskrankenhaus Günzburg Germany (DE) University of Tennessee (UTK) United States (USA) (US) MedStar Health United States (USA) (US) University of Illinois at Urbana-Champaign United States (USA) (US) University of Cincinnati United States (USA) (US) University of Chicago United States (USA) (US)

How to cite

APA:

Kuramatsu, J., Gerner, S., Ziai, W., Bardutzky, J., Sembill, J., Sprügel, M.,... Huttner, H. (2022). Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis. Stroke, 53(9), 2876-2886. https://dx.doi.org/10.1161/STROKEAHA.121.038455

MLA:

Kuramatsu, Joji, et al. "Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis." Stroke 53.9 (2022): 2876-2886.

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