Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis.
fibrinolysis
hydrocephalus
intracerebral hemorrhage
mortality
standard of care
Journal
Stroke
ISSN: 1524-4628
Titre abrégé: Stroke
Pays: United States
ID NLM: 0235266
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
pubmed:
7
5
2022
medline:
25
8
2022
entrez:
6
5
2022
Statut:
ppublish
Résumé
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. 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). 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 35521958
doi: 10.1161/STROKEAHA.121.038455
pmc: PMC9398945
mid: NIHMS1807062
doi:
Substances chimiques
Fibrinolytic Agents
0
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2876-2886Subventions
Organisme : NINDS NIH HHS
ID : U01 NS062851
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Investigateurs
Lauren Sansing
(L)
Charles C Matouk
(CC)
Audrey Leasure
(A)
Jan Sobesky
(J)
Miriam Bauer
(M)
Johannes Schurig
(J)
Timolaos Rizos
(T)
Karl Georg Haeusler
(KG)
Wolfgang Müllges
(W)
Peter Kraft
(P)
Anna-Lena Schubert
(AL)
Sebastian Stösser
(S)
Albert Christian Ludolph
(AC)
Martin Nueckel
(M)
Jörg Glahn
(J)
Henning Stetefeld
(H)
Jan Rahmig
(J)
Anna Lena Fisse
(AL)
Peter Michels
(P)
Henning Schwert
(H)
Georg Hagemann
(G)
Florian Rakers
(F)
Johannes C Wöhrle
(JC)
Fahid Alshammari
(F)
Markus Horn
(M)
Dirk Bahner
(D)
Christian Urbanek
(C)
Frederick Palm
(F)
Armin Grau
(A)
Références
Lancet. 2017 Feb 11;389(10069):603-611
pubmed: 28081952
JAMA. 2016 Sep 27;316(12):1279-88
pubmed: 27673305
JAMA. 2019 Feb 12;321(6):602-603
pubmed: 30676631
BMJ. 2016 Oct 12;355:i4919
pubmed: 27733354
Crit Care Med. 2019 Aug;47(8):1125-1134
pubmed: 31162192
JAMA. 2015 Apr 28;313(16):1657-65
pubmed: 25919529
JAMA. 2020 Feb 18;323(7):666
pubmed: 32068814
JAMA. 2015 Feb 24;313(8):824-36
pubmed: 25710659
JAMA Cardiol. 2018 Oct 1;3(10):905-906
pubmed: 30073250
Stroke. 2021 Mar;52(3):975-984
pubmed: 33517701
Stroke. 2011 Nov;42(11):3009-16
pubmed: 21868730
Crit Care Med. 2019 Feb;47(2):176-185
pubmed: 30543566
Stroke. 2013 Oct;44(10):e120-5
pubmed: 24021679
Lancet. 2005 Jan 1-7;365(9453):82-93
pubmed: 15639683
Stat Med. 2019 Feb 10;38(3):326-338
pubmed: 30284314
Intensive Care Med. 2015 Feb;41(2):348-50
pubmed: 25578679
Stroke. 2019 Jul;50(7):1688-1695
pubmed: 31177984
JAMA. 2019 Oct 8;322(14):1392-1403
pubmed: 31593272
Acta Neurol Scand. 2011 Nov;124(5):343-8
pubmed: 21303348
Neurocrit Care. 2013 Jun;18(3):354-61
pubmed: 23463422
Stroke. 2015 Jul;46(7):2032-60
pubmed: 26022637
Ann Neurol. 2021 Mar;89(3):474-484
pubmed: 33222266
Int J Stroke. 2018 Jan;13(1):11-23
pubmed: 28920538
Intensive Care Med. 2002 Oct;28 Suppl 2:S235-40
pubmed: 12404092
Science. 2020 Oct 2;370(6512):50-56
pubmed: 33004510
Stroke. 2013 Feb;44(2):362-6
pubmed: 23306318
Lancet. 2018 Oct 6;392(10154):1257-1268
pubmed: 30319113
Am J Hypertens. 2017 Jul 1;30(7):719-727
pubmed: 28430838
Int J Epidemiol. 2017 Feb 1;46(1):103-105
pubmed: 27272186
Cerebrovasc Dis Extra. 2019;9(2):77-89
pubmed: 31408859
PLoS Med. 2015 Jul 21;12(7):e1001855
pubmed: 26196287
Semin Respir Crit Care Med. 2017 Dec;38(6):745-759
pubmed: 29262432
Stroke. 2014 Sep;45(9):2662-9
pubmed: 25052321
Int J Stroke. 2014 Oct;9(7):840-55
pubmed: 25156220
J Neurol. 2018 Dec;265(12):2803-2814
pubmed: 30242743
JAMA. 2000 Apr 19;283(15):2008-12
pubmed: 10789670
Neurosurgery. 2010 Apr;66(4):648-55
pubmed: 20305489
JAMA Neurol. 2019 Dec 1;76(12):1426-1427
pubmed: 31424478
Intensive Care Med. 2010 Feb;36(2):264-71
pubmed: 19838669
Eur J Neurol. 2008 Apr;15(4):342-9
pubmed: 18312407
Ann Neurol. 2018 Jan;83(1):186-196
pubmed: 29314216