Safety and efficacy of active blood-pressure reduction to the recommended thresholds for intravenous thrombolysis in patients with acute ischaemic stroke in the Netherlands (TRUTH): a prospective, observational, cluster-based, parallel-group study. (2024)

Afiliação

• Zonneveld TP; Department of Neurology, Amsterdam University Medical Centers, location AMC, Amsterdam, Netherlands.
• Vermeer SE; Department of Neurology, Rijnstate Hospital, Arnhem, Netherlands.
• van Zwet EW; Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands.
• Groot AED; Department of Neurology, Amsterdam University Medical Centers, location AMC, Amsterdam, Netherlands.
• Algra A; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands; Julius Center, University Medical Center Utrecht, Netherlands; Department of Neurology and Neurosurgery, Brain Center, University Medical Center Utrecht, Netherlands.
• Aerden LAM; Department of Neurology, Reinier de Graaf Gasthuis, Delft, Netherlands.
• Alblas KCL; Department of Neurology, Franciscus Gasthuis and Vlietland, Rotterdam, Netherlands.
• de Beer F; Department of Neurology, Spaarne Gasthuis, Haarlem, Netherlands.
• Brouwers PJAM; Department of Neurology, Medisch Spectrum Twente, Enschede, Netherlands.
• de Gans K; Department of Neurology, Groene Hart Hospital, Gouda, Netherlands.
• van Gemert HMA; Department of Neurology, Meander MC, Amersfoort, Netherlands.
• van Ginneken BCAM; Department of Neurology, Maxima MC, Veldhoven, Netherlands.
• Grooters GS; Department of Neurology, Elkerliek, Helmond, Netherlands.
• Halkes PHA; Department of Neurology, Noordwest Ziekenhuisgroep, Alkmaar, Netherlands.
• van der Heijden-Montfroy TAMHG; Department of Neurology, VieCuri, Venlo, Netherlands.
• Jellema K; Department of Neurology, Haaglanden Medisch Centrum, The Hague, Netherlands; University Neurovascular Center Leiden-the Hague, Leiden, Netherlands; University Neurovascular Center Leiden-the Hague, the Hague, Netherlands.
• de Jong SW; Department of Neurology, St Jansdal Hospital, Harderwijk, Netherlands.
• Lövenich-Ciccarello H; Department of Neurology, St Jans Gasthuis, Weert, Netherlands.
• van der Meulen WDM; Department of Neurology, Red Cross Hospital, Beverwijk, Netherlands.
• Peters EW; Department of Neurology, Admiraal de Ruyter Hospital, Vlissingen, Netherlands.
• van der Ree TC; Department of Neurology, Dijklander Hospital, Hoorn, Netherlands.
• Remmers MJM; Department of Neurology, Amphia Hospital, Breda, Netherlands.
• Richard E; Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands.
• Rovers JMP; Department of Neurology, Gelderse Vallei Hospital, Ede, Netherlands.
• Saxena R; Department of Neurology, Maasstad Hospital, Rotterdam, Netherlands.
• van Schaik SM; Department of Neurology, OLVG, Amsterdam, Netherlands.
• Schonewille WJ; Department of Neurology, St Antonius Hospital, Nieuwegein, Netherlands.
• Schreuder TAHCML; Department of Neurology, Zuyderland MC, Heerlen, Netherlands.
• de Schryver ELLM; Department of Neurology, Alrijne Hospital, Leiderdorp, Netherlands.
• Schuiling WJ; Department of Neurology, MC Leeuwarden, Leeuwarden, Netherlands.
• Spaander FH; Department of Neurology, Zaans MC, Zaandam, Netherlands.
• van Tuijl JH; Department of Neurology, Elisabeth-Tweesteden Hospital, Tilburg, Netherlands.
• Visser MC; Department of Neurology, Amsterdam University Medical Centers, location AMC, Amsterdam, Netherlands.
• Zinkstok SM; Department of Neurology, Tergooi MC, Hilversum, Netherlands.
• Zock E; Department of Neurology, Albert Schweitzer Hospital, Dordrecht, Netherlands.
• Dippel DWJ; Department of Neurology, Erasmus MC, Rotterdam, Netherlands.
• Kappelle LJ; Department of Neurology and Neurosurgery, Brain Center, University Medical Center Utrecht, Netherlands.
• van Oostenbrugge RJ; Department of Neurology, Maastricht UMC+, Maastricht, Netherlands; Cardiovascular Research Institute Maastricht, Maastricht UMC+, Maastricht, Netherlands.
• Roos YBWEM; Department of Neurology, Amsterdam University Medical Centers, location AMC, Amsterdam, Netherlands.
• Vermeij FH; Department of Neurology, Franciscus Gasthuis and Vlietland, Rotterdam, Netherlands.
• Wermer MJH; Department of Neurology, UMC Groningen, Groningen, Netherlands.
• van der Worp HB; Department of Neurology and Neurosurgery, Brain Center, University Medical Center Utrecht, Netherlands.
• Nederkoorn PJ; Department of Neurology, Amsterdam University Medical Centers, location AMC, Amsterdam, Netherlands.
• Kruyt ND; Department of Neurology, Leiden University Medical Center, Leiden, Netherlands; University Neurovascular Center Leiden-the Hague, Leiden, Netherlands; University Neurovascular Center Leiden-the Hague, the Hague, Netherlands. Electronic address: n.d.kruyt@lumc.nl.

ABSTRACT

BACKGROUND:

Intravenous thrombolysis is contraindicated in patients with ischaemic stroke with blood pressure higher than 185/110 mm Hg. Prevailing guidelines recommend to actively lower blood pressure with intravenous antihypertensive agents to allow for thrombolysis; however, there is no robust evidence for this strategy. Because rapid declines in blood pressure can also adversely affect clinical outcomes, several Dutch stroke centres use a conservative strategy that does not involve the reduction of blood pressure. We aimed to compare the clinical outcomes of both strategies.

METHODS:

Thrombolysis and Uncontrolled Hypertension (TRUTH) was a prospective, observational, cluster-based, parallel-group study conducted across 37 stroke centres in the Netherlands. Participating centres had to strictly adhere to an active blood-pressure-lowering strategy or to a non-lowering strategy. Eligible participants were adults (≥18 years) with ischaemic stroke who had blood pressure higher than 185/110 mm Hg but were otherwise eligible for intravenous thrombolysis. The primary outcome was functional status at 90 days, measured using the modified Rankin Scale and assessed through telephone interviews by trained research nurses. Secondary outcomes were symptomatic intracranial haemorrhage, the proportion of patients treated with intravenous thrombolysis, and door-to-needle time. All ordinal logistic regression analyses were adjusted for age, sex, stroke severity, endovascular thrombectomy, and baseline imbalances as fixed-effect variables and centre as a random-effect variable to account for the clustered design. Analyses were done according to the intention-to-treat principle, whereby all patients were analysed according to the treatment strategy of the participating centre at which they were treated.

FINDINGS:

Recruitment began on Jan 1, 2015, and was prematurely halted because of a declining inclusion rate and insufficient funding on Jan 5, 2022. Between these dates, we recruited 853 patients from 27 centres that followed an active blood-pressure-lowering strategy and 199 patients from ten centres that followed a non-lowering strategy. Baseline characteristics of participants from the two groups were similar. The 90-day mRS score was missing for 15 patients. The adjusted odds ratio (aOR) for a shift towards a worse 90-day functional outcome was 1·27 (95% CI 0·96-1·68) for active blood-pressure reduction compared with no active blood-pressure reduction. 798 (94%) of 853 patients in the active blood-pressure-lowering group were treated with intravenous thrombolysis, with a median door-to-needle time of 35 min (IQR 25-52), compared with 104 (52%) of 199 patients treated in the non-lowering group with a median time of 47 min (29-78). 42 (5%) of 852 patients in the active blood-pressure-lowering group had a symptomatic intracranial haemorrhage compared with six (3%) of 199 of those in the non-lowering group (aOR 1·28 [95% CI 0·62-2·62]).

INTERPRETATION:

Insufficient evidence was available to establish a difference between an active blood-pressure-lowering strategy-in which antihypertensive agents were administered to reduce blood pressure below 185/110 mm Hg-and a non-lowering strategy for the functional outcomes of patients with ischaemic stroke, despite higher intravenous thrombolysis rates and shorter door-to-needle times among those in the active blood-pressure-lowering group. Randomised controlled trials are needed to inform the use of an active blood-pressure-lowering strategy.

FUNDING:

Fonds NutsOhra.