Clinical Impact of the Use of IMPROVE for Selection of Patients for Carotid Revascularisation: a Randomized Controlled Multicentre Non-inferiority Trial in Symptomatic Patients With 30-99% Carotid Stenosis
Clinical Impact of the Use of IMPROVE for Selection of Patients for Carotid Revascularisation: a Randomized Controlled Multicentre Non-inferiority Trial in Symptomatic Patients With 30-99% Carotid Stenosis
Narrowing of the carotid artery due to atherosclerosis with an unstable plaque can cause a stroke. Patients with carotid artery disease who have had a TIA or minor stroke and are at high risk of another stroke are often treated with surgery or stenting to remove the plaque. For lower-risk patients, medication alone is the better option, as surgery also carries risks. A new decision method, based on MRI detection of unstable plaques (IMPROVE), can better assess stroke risk and help determine which patients do or do not need surgery. We are investigating whether this method is at least as effective as the standard approach, which mainly considers the degree of narrowing. We expect that this new method will help reduce strokes and lower healthcare costs.
Patients will be followed for several years to compare which method is better for health and costs.
SUMMARY:
Stroke is the 2nd leading global cause of death and disability. Rupture of a vulnerable carotid plaque causes ~20% of ischemic strokes. Symptomatic patients with carotid stenosis may benefit from surgical removal of the plaque or stenting (revascularisation) to prevent recurrent stroke, but this carries risks. Current patient selection for revascularisation is suboptimal, largely based on stenosis degree without considering plaque vulnerability. Improving risk prediction is therefore crucial and has been formally recognized as a key priority in the Dutch Society for Vascular Surgery's Knowledge Agenda (2022): "How can we better identify patients with carotid stenosis who would or would not benefit from revascularisation?" Presence of intraplaque haemorrhage (IPH) on MRI is one of the most powerful imaging biomarkers of plaque vulnerability and a superior predictor of stroke compared to traditional clinical factors, including degree of stenosis. The recently developed "Individualized MRI- Based Stroke Prediction Score Using Plaque Vulnerability for Symptomatic Carotid Artery Disease Patients" (IMPROVE) clinical prediction model integrates both IPH on MRI and clinical risk factors to calculate ipsilateral ischemic stroke risk. This model has demonstrated significantly improved predictive performance over existing scores. A recent decision-analytic study investigated the impact of the use of IMPROVE to select patients with high stroke risk for revascularisation plus OMT (medication and lifestyle advice) and low-risk patients for OMT (optimized medical therapy)-only. This decision-analytic study showed that implementation of the IMPROVE decision rule for revascularisation selection can lead to 35% less ipsilateral strokes and perioperative strokes and deaths and a lifetime cost reduction of €6101 per patient, equating to an annual reduction in societal healthcare costs of €18 million in the Netherlands alone.
Rationale: Patient selection for carotid revascularisation to prevent recurrent strokes could be optimised by providing clinicians and patients the IMPROVE score for shared decision-making. Objective: The primary objective is to investigate the clinical impact and the cost-effectiveness of the individualised MRI-based IMPROVE decision rule compared to care as usual (CAU) in the selection of TIA and non-disabling stroke patients with 30-99% carotid stenosis for revascularisation.
Study design: Multicentre, randomized controlled non-inferiority trial. Study population: Patients with a recent TIA or minor ischemic stroke and ipsilateral 30-99% carotid stenosis according to NASCET criteria.
Intervention: For patients that are randomised to the IMPROVE arm, the IMPROVE risk score will be provided as additional information for clinical decision-making on patient stratification for carotid revascularisation plus OMT versus OMT-only. A revascularization procedure in combination with OMT will be advised for patients at high ipsilateral stroke risk (≥10% within 3 years) according to the IMPROVE score, while OMT- only (medication and lifestyle advice) is advised to patients with lower risk scores.
Comparator: Patients randomised for the control arm (care-as-usual (CAU)) will be selected for revascularisation based on the guidelines for carotid interventions from the European Society for Vascular Surgery. It advises to consider revascularisation for TIA and stroke patients with ≥50% carotid stenosis. Patients with 30-49% stenosis are treated by OMT-only (medication and lifestyle advice). Plaque vulnerability is not taken into account for patient selection in current clinical care in the Netherlands.
Main study parameters/endpoints: Primary: Composite of any stroke or death within 44 days after randomisation or ipsilateral ischemic stroke at any time during subsequent 3-5 years follow up. Secondary: a.o. QALYs, number of revascularization procedures, costs.
Inclusion Criteria:
Exclusion Criteria:
improve.trial@mumc.nl+31 43 387 4911
robin.pleumeekers@mumc.nl+31 43 387 7622
Arnhem, Gelderland 6800 TA, Netherlands
SVermeer@rijnstate.nl
MCMSimons@Rijnstate.nl
floris.schreuder@radboudumc.nl
t.schreuder@zuyderland.nl
s.liedekerken@zuyderland.nl
robin.pleumeekers@mumc.nl+31 43 387 7622
juul.bierens@maastrichtuniversity.nl
p.j.nederkoorn@amsterdamumc.nl
c.j.b.a.kersten@isala.nl
H.Kerkhoff@asz.nl
d.bos@erasmusmc.nl
h.nolen@erasmusmc.nl
k.jellema@haaglandenmc.nl
g.j.deborst-2@umcutrecht.nl