Rationale and aim

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. In the Netherlands, carotid endarterectomy accounts for 95% of revascularisation procedures performed in symptomatic patients. Current patient selection for revascularisation is suboptimal, largely based on stenosis degree without considering plaque vulnerability. 

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-only. This decision-analytic study showed that implementation of the IMPROVE decision rule for revascularisation selection can lead to 35% less strokes 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.
 

Patient selection for carotid revascularisation to prevent recurrent strokes could be optimised by providing clinicians and patients the IMPROVE score for shared decision-making. This randomized controlled multicentre non-inferiority trial will investigate two carotid revascularization selection strategies in symptomatic patients with 30-99% carotid stenosis:

● Risk stratification as in standard care

● Risk stratification using the IMPROVE risk score

The primary objective is to evaluate the clinical impact and the cost-effectiveness of the individualised MRI-based IMPROVE decision rule compared to CAU in the selection of TIA and non-disabling stroke patients with ipsilateral 30-99% atheromatous carotid artery stenosis for revascularisation.

Our hypothesis is that the IMPROVE decision rule is non-inferior to CAU in terms of the primary outcome (composite of any stroke or death within 44 days after randomisation or ipsilateral ischemic stroke at any time during subsequent follow-up) while significantly reducing associated costs.

Secondary objectives:

● To compare QALYs and costs associated with IMPROVE-based care and CAU.

● To investigate and evaluate the willingness of clinicians and patients to use the IMPROVE decision rule to estimate the patient’s risk of stroke recurrence.