Treatment restrictions after acute stroke across nine European countries and their association with 90-day mortality: a post hoc analysis of the PRECIOUS randomised controlled trial.
14 affiliations
- 1Department of Neurology and Neurosurgery, Brain Center, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands.
- 2Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands.
- 3Department of Neurology, St. Antonius Ziekenhuis, Soestwetering 1, 3543 AZ, Utrecht, the Netherlands.
- 4Department of Neurology, Spaarne Gasthuis, Boerhaavelaan 22, 2035 RC, Haarlem, the Netherlands.
- 5First Propaedeutic Department of Internal Medicine, AHEPA Hospital, Aristoteles University of Thessaloniki, Greece.
- 6Department of Neurology and Neurosurgery, University of Tartu, L. Puusepa 8, 50406, Tartu, Estonia.
- 7Department of Neurology, Oslo University Hospital, Sognsvannsveien 20, 0372, Oslo, Norway.
- 8Department of Neurology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
- 9Department of Neurology, University of Debrecen, Nagyerdei krt. 98, 4032, Debrecen, Hungary.
- 10Department of Neurology and Stroke Unit, ASST di Mantova, Strada Lago Paiolo 10, 46100, Mantova, Italy.
- 11Department of Neurology and Stroke Unit, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127, Bergamo, Italy.
- 122nd Department of Neurology, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957, Warsaw, Poland.
- 13Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, EH16 4SB, Edinburgh, United Kingdom.
- 14Stroke Trials Unit, Mental Health & Clinical Neuroscience, University of Nottingham, C Floor, South Block, Queen's Medical Centre, Derby Road, NG7 2UH, Nottingham, United Kingdom.
Abstract
Background
In patients with acute stroke, early withholding or withdrawal of life-sustaining therapies is associated with an increased risk of death. We used practice variation across nine European countries to assess whether this relation may be causal.Methods
We performed a post hoc analysis of the PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke (PRECIOUS) trial, a randomised clinical trial of metoclopramide, paracetamol, and/or ceftriaxone started within 24 h of symptom onset in older patients with acute ischaemic stroke or intracerebral haemorrhage (ISRCTN82217627). The frequency of early treatment restrictions, defined as those installed within 24 h after randomisation, was calculated per participating country and their relation with the primary outcome 'death at 90 days' was estimated through: 1) adjustment for confounders with regression analysis with inverse-propensity score reweighting; and 2) comparing patients enrolled in countries with and without early restrictions, adjusted for confounders with regression analysis.Findings
Of 1493 patients enrolled in PRECIOUS between 2016 and 2022, 1451/1493 (97%) were included in this analysis, of whom 276/1451 (19%) had an early treatment restriction. The rate of these restrictions ranged from 0% to 48% across the participating countries. Patients with restrictions were more likely to die within 90 days (inverse propensity-weighted odds ratio (OR) 3.39; 95% CI 2.71-4.25). However, there was no difference in the rate of death at 90 days between countries with and those without restrictions (21.3% vs 23.5%, adjusted OR 1.39; 95% CI 0.8-2.39).Interpretation
The use of treatment restrictions early after stroke varied widely across Europe. Although restrictions were independently associated with an increased rate of death, the comparison of death rates between countries with and those without such restrictions provides no indication that this relation is causal.Funding
European Union's Horizon 2020 research and innovation programme; grant agreement No. 634809.
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BibTeX
@article{sluis2026treatment,
title = {{Treatment restrictions after acute stroke across nine European countries and their association with 90-day mortality: a post hoc analysis of the PRECIOUS randomised controlled trial.}},
author = {Wouter M Sluis and Wouter A C van Amsterdam and Jeroen C de Jonge and Hendrik Reinink and George Ntaios and Janika Kõrv and Anne Hege Aamodt and Götz Thomalla and Laszlo Csiba and Alfonso Ciccone and Iwona Kurkowska-Jastrzebska and Malcolm R Macleod and Philip M Bath and H Bart van der Worp and PRECIOUS investigatorso and PRECIOUS investigators},
journal = {The Lancet regional health. Europe},
year = {2026},
month = oct,
doi = {10.1016/j.lanepe.2026.101894},
url = {https://europepmc.org/article/MED/42926861},
note = {CC BY},
}
RIS
TY - JOUR
TI - Treatment restrictions after acute stroke across nine European countries and their association with 90-day mortality: a post hoc analysis of the PRECIOUS randomised controlled trial.
AU - Wouter M Sluis
AU - Wouter A C van Amsterdam
AU - Jeroen C de Jonge
AU - Hendrik Reinink
AU - George Ntaios
AU - Janika Kõrv
AU - Anne Hege Aamodt
AU - Götz Thomalla
AU - Laszlo Csiba
AU - Alfonso Ciccone
AU - Iwona Kurkowska-Jastrzebska
AU - Malcolm R Macleod
AU - Philip M Bath
AU - H Bart van der Worp
AU - PRECIOUS investigatorso
AU - PRECIOUS investigators
PY - 2026
DA - 2026/10/14
JO - The Lancet regional health. Europe
DO - 10.1016/j.lanepe.2026.101894
UR - https://europepmc.org/article/MED/42926861
AB - Background In patients with acute stroke, early withholding or withdrawal of life-sustaining therapies is associated with an increased risk of death. We used practice variation across nine European countries to assess whether this relation may be causal.Methods We performed a post hoc analysis of the PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke (PRECIOUS) trial, a randomised clinical trial of metoclopramide, paracetamol, and/or ceftriaxone started within 24 h of symptom onset in older patients with acute ischaemic stroke or intracerebral haemorrhage (ISRCTN82217627). The frequency of early treatment restrictions, defined as those installed within 24 h after randomisation, was calculated per participating country and their relation with the primary outcome 'death at 90 days' was estimated through: 1) adjustment for confounders with regression analysis with inverse-propensity score reweighting; and 2) comparing patients enrolled in countries with and without early restrictions, adjusted for confounders with regression analysis.Findings Of 1493 patients enrolled in PRECIOUS between 2016 and 2022, 1451/1493 (97%) were included in this analysis, of whom 276/1451 (19%) had an early treatment restriction. The rate of these restrictions ranged from 0% to 48% across the participating countries. Patients with restrictions were more likely to die within 90 days (inverse propensity-weighted odds ratio (OR) 3.39; 95% CI 2.71-4.25). However, there was no difference in the rate of death at 90 days between countries with and those without restrictions (21.3% vs 23.5%, adjusted OR 1.39; 95% CI 0.8-2.39).Interpretation The use of treatment restrictions early after stroke varied widely across Europe. Although restrictions were independently associated with an increased rate of death, the comparison of death rates between countries with and those without such restrictions provides no indication that this relation is causal.Funding European Union's Horizon 2020 research and innovation programme; grant agreement No. 634809.
SN - 2666-7762
ER -