TY - JOUR
T1 - Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage
T2 - An Individual Participant Data Meta-Analysis
AU - Kuramatsu, Joji B.
AU - Gerner, Stefan T.
AU - Ziai, Wendy
AU - Bardutzky, Jürgen
AU - Sembill, Jochen A.
AU - Sprügel, Maximilian I.
AU - Mrochen, Anne
AU - Kölbl, Kathrin
AU - Ram, Malathi
AU - Avadhani, Radhika
AU - Falcone, Guido J.
AU - Selim, Magdy H.
AU - Lioutas, Vasileios Arsenios
AU - Endres, Matthias
AU - Zweynert, Sarah
AU - Vajkoczy, Peter
AU - Ringleb, Peter A.
AU - Purrucker, Jan C.
AU - Volkmann, Jens
AU - Neugebauer, Hermann
AU - Erbguth, Frank
AU - Schellinger, Peter D.
AU - Knappe, Ulrich J.
AU - Fink, Gereon R.
AU - Dohmen, Christian
AU - Minnerup, Jens
AU - Reichmann, Heinz
AU - Schneider, Hauke
AU - Röther, Joachim
AU - Reimann, Gernot
AU - Schwarz, Michael
AU - Bäzner, Hansjörg
AU - Claßen, Joseph
AU - Michalski, Dominik
AU - Witte, Otto W.
AU - Günther, Albrecht
AU - Hamann, Gerhard F.
AU - Lücking, Hannes
AU - Dörfler, Arnd
AU - Ishfaq, Muhammad Fawad
AU - Chang, Jason J.
AU - Testai, Fernando D.
AU - Woo, Daniel
AU - Alexandrov, Andrei V.
AU - Staykov, Dimitre
AU - Goyal, Nitin
AU - Tsivgoulis, Georgios
AU - Sheth, Kevin N.
AU - Awad, Issam A.
AU - Schwab, Stefan
AU - Hanley, Daniel F.
AU - Huttner, Hagen B.
N1 - Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/9/1
Y1 - 2022/9/1
N2 - 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.
AB - 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.
KW - fibrinolysis
KW - hydrocephalus
KW - intracerebral hemorrhage
KW - mortality
KW - standard of care
UR - http://www.scopus.com/inward/record.url?scp=85136465278&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85136465278&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.121.038455
DO - 10.1161/STROKEAHA.121.038455
M3 - Article
C2 - 35521958
AN - SCOPUS:85136465278
SN - 0039-2499
VL - 53
SP - 2876
EP - 2886
JO - Stroke
JF - Stroke
IS - 9
ER -