StAtins in Frail OldEr Patients with Ischemic Stroke or Transient Ischemic Attack - the Randomized Controlled Trial

Phase 4

Not yet recruiting

• Conditions: Ischemic Stroke; Transient Ischemic Attack
• Interventions: Drug: Statin (atorvastatin, fluvastatin, pravastatin, rosuvastatin or simvastatin)

• Registration Number: NCT06785727
• Lead Sponsor: Prof. dr. Nathalie van der Velde

Brief Summary

Two Dutch guidelines (Stroke and Cardiovascular Risk Management) provide conflicting advice on optimal statin treatment in older patients. In the SAFEST - RCT, the investigators will assess the impact of starting versus not starting a statin in frail individuals aged 70 and above with a recent ischemic stroke or transient ischemic attack (TIA) on their health-related quality of life and Major Adverse Cardiovascular Events (MACE) free survival during a two-year follow-up period.

Detailed Description

Objective: To assess the impact of starting versus not starting a statin in frail individuals aged 70 and above with a recent ischemic stroke or transient ischemic attack (TIA) on their health-related quality of life and MACE free survival during a two-year follow-up period.

Study population: The patient population consists of frail older (\>=70 yrs) patients with a recent acute ischemic stroke or TIA who are admitted to the hospital or visit the outpatient clinic or emergency department for diagnostic evaluation, and who were not receiving statin treatment at the time of the acute event. Frailty is defined by a pre-event Clinical Frailty Scale (CFS) score of 4-7 and/or a post-event score of 6-7.

Description of intervention(s): Participants in the intervention group will start with a statin with target values following the Dutch stroke guideline. The control group will not start with a statin, aligning with the Dutch Cardiovascular Risk Management (CVRM) guideline recommendations.

Outcome measures:

This study has two co-primary endpoints: (1) Health-Related Quality of Life (HrQoL), using the Patient-Reported Outcomes Measurement Information System - Global-10 (PROMIS-10) and (2) Major Adverse Cardiovascular Events (MACE) free survival, after 2 years. We will evaluate these two co-primary outcomes at multiple time points, specifically at 3, 6, 12, 18, and 24 months. For patients enrolled in the beginning of recruitment, an extended follow-up of three years will be conducted to provide additional insights into the two primary endpoints.

Study Timeline

• Study First Submitted: 2023-01-16
• Status Verified: 2025-01
• Study First Submitted QC: 2025-01-19
• Last Update Submitted: 2025-01-19
• Study First Posted: 2025-01-21
• Last Update Posted: 2025-01-21
• Study Start: 2025-02-01
• Primary Completion: 2028-12-01
• Study Completion: 2029-07-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 612

Inclusion Criteria

• age = 70 years or older at the time of ischemic stroke or TIA;
• inclusion within 6 weeks after diagnosis of ischemic stroke or TIA;
• not using statin therapy at the time of the index event;
• frailty as defined by a pre-event score of 4-7 and/or post-event score of 6-7 on the validated Clinical Frailty Scfale.[49]

Exclusion Criteria

• Patients with a stroke or TIA of non-atherosclerotic etiology.
• Previous serious adverse drug reactions (defined as an adverse reaction that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or is a birth defect40) to statins or other contraindications to statin use.
• Very severe frailty or very limited life expectancy (< 6 months) as defined by a score >= 8 points on the validated Clinical Frailty Scale.
• Inability to communicate in Dutch.
• Inability to respond to questions, either independently or with the assistance of a proxy (a proxy is allowed to assist by writing on behalf of the participant in cases of physical incapacity or by discussing questions with the participant, but the proxy cannot make decisions for the participant).
• Inability or unwillingness to provide written informed consent, either independently or with the assistance of a proxy (a proxy is allowed to assist by writing on behalf of the participant in cases of physical incapacity or by discussing the consent form with the participant, but the proxy cannot make decisions or provide consent on behalf of the participant).
• Extremely high-risk patients, i.e. patients who have had two or more cardiovascular events within a period of one year.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prescribing a statin	Statin (atorvastatin, fluvastatin, pravastatin, rosuvastatin or simvastatin)	Newly prescribing a statin

Primary Outcome Measures

Name	Time	Method
Health-Related Quality of Life (HrQoL)	3, 6, 12, 18, 24 (and 36) months.	This will be measured using the PROMIS-10 scale scores (ranging from 0 to 100, with higher scores indicating better health), including global mental health and global physical health subscales. Measurements at 3, 6, 12, 18, 24 (and 36) months.
Major Adverse Cardiovascular Events (MACE) free survival	3, 6, 12, 18, 24 (and 36) months.	Classical 3-point MACE (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and non-cardiovascular death. Measurements at3, 6, 12, 18, 24 (and 36) months.

Secondary Outcome Measures

Name	Time	Method
Functional Outcome	1 and 2 years	This will be assessed using the modified Rankin Scale (mRS) 49, with scores ranging from 0 to 6 (lower scores indicating better function).
Cognition MoCA	1 and 2 years	will be measured using the Montreal Cognitive Assessment (MoCA)51 or the Telephone version of the MoCA (T-MOCA)
Number of falls	1 and 2 years	Falls, measured using the falls calender. Participant returns the fall calender every 3 months.
Time to first fall	2 years	Falls, measured using the falls calender. Participant returns the fall calender every 3 months.
General quality of life EuroQol Questionnaire (EQ-5D-5L)	1 and 2 years	General QoL measure by EuroQol Questionnaire (EQ-5D-5L). This will be used to calculate the cost-effectiveness analysis (CAE). Possible scores range from 0-100, the higher, the better.
Societal costs	1 and 2 years	Societal costs measured by The Older Persons and Informal Caregivers Survey - Minimum Data Set (TOPICS-MDS) (questions 23 - 37)
Cardiovascular Risk Status	1 and 2 years	method of assessing is to be decided.