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

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.