Statins in Frail Older Patients with Ischemic Stroke or Transient Ischemic Attack - the Prospective Cohort Study (SAFEST-coh)

StAtins in Frail OldEr Patients with Ischemic Stroke or Transient Ischemic Attack - the Prospective Cohort Study

Two Dutch guidelines (Stroke and Cardiovascular Risk Management) provide conflicting advice on optimal statin treatment in older patients. In the SAFEST-cohort, the investigators will assess the impact of continuing versus discontinuing 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 Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; TIA
• Intervention / Treatment: Drug: Statin

Detailed Description

The stroke incidence strongly increases with age.Many of the older individuals that suffered a stroke will have to live with stroke sequelae and will need lifelong care, either at home or in a nursing facility.

Hence, secondary prevention strategies are of the highest importance. Statins are used for the prevention of subsequent cardiovascular events in ischemic stroke and TIA patients. The efficacy of statin therapy has been firmly established in middle-aged stroke patients. However, despite the high prevalence of stroke in older people, the evidence for the efficacy of statin therapy in older individuals that suffered an ischemic stroke or TIA is sparse. This primarily arises from the underrepresentation of older patients in statin trials.

In a recent meta-analysis, it was found that in people aged 70 and above, statin use lowered the annual incidence of major vascular events with approximately one percent. However, the trials in this meta-analysis mostly included fit, non-frail older adults.

Frailty is a geriatric condition characterized by an increased vulnerability to external stressors, linked to adverse outcomes, including premature mortality. A considerable proportion of the older population is frail. However, since trials that include older individuals often focus on fit, non-frail older adults, there is currently no evidence for the most effective treatment strategy in the frail older group.

While it might be tempting to extrapolate the benefits of statin therapy from younger patients to frail older patients, it is vital to acknowledge the considerable disparities between these groups. Firstly, frail older stroke survivors may not have a life-expectancy longer than the time to benefit. Secondly, due to the high percentage of polypharmacy in frail older people, this patient group has a higher risk for the occurrence of drug-drug interactions and adverse effects, which have the ability to significantly affect the quality of life.

The limited body of evidence regarding the effectiveness of statins in the older population, combined with their higher susceptibility to side effects and drug interactions, results in uncertainty for patients as well as for doctors and policymakers when deciding how to treat this patient group.This uncertainty is clearly reflected in the two Dutch guidelines ("Herseninfarct en Hersenbloeding" and "Cardiovascular Risk Management (CVRM)" respectively), providing conflicting advice on optimal statin treatment in older patients.

The investigators hypothesize that in frail older patients with a recent ischemic stroke or TIA, discontinuing statins will increase health-related quality of life (HrQoL) without a substantial decrease in Major Adverse Cardiovascular Events (MACE) free survival, which includes cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke.

In this prospective cohort study, no intervention will be implemented. Participants will be followed for two years (and for the patients included in the first years of the inclusion period - three). During this time, data is collected including questionnaires on quality of life, occurrence of MACE or falls, and possible changes in statin treatment.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Susanna R Prins, MSc; Phone Number: 0031 20 566 9111; Email: s.r.prins@amsterdamumc.nl
• Study Contact Backup: Name: Birgit A Damoiseaux-Volman, PhD; Phone Number: 0031 20 566 9111; Email: b.a.damoiseaux@amsterdamumc.nl

Study Locations

• Netherlands
  • Almere, Netherlands
    • Recruiting
    • Flevoziekenhuis
    • Contact: Elizabeth Osei, MD, PHD; Phone Number: 0031368688720; Email: losei@flevoziekenhuis.nl
  • Amsterdam, Netherlands
    • Recruiting
    • Amsterdam UMC, location AMC
    • Contact: Susanna Prins, MD; Phone Number: 0031205669111; Email: s.r.prins@amsterdamumc.nl
  • Eindhoven, Netherlands
    • Recruiting
    • Catharina Ziekenhuis
    • Contact: Rob Gons, MD, PHD; Phone Number: 031402399426; Email: rob.gons@catharinaziekenhuis.nl
  • Zwolle, Netherlands
    • Recruiting
    • Isala Klinieken
    • Contact: Wilmar Jolink, MD, PHD; Phone Number: 0031886242461; Email: w.m.t.jolink@isala.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

frail individuals aged 70 and above with a recent ischemic stroke or transient ischemic attack (TIA)

Description

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;
• already 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 Scale.

Exclusion Criteria:

• Previous serious adverse drug reactions (defined as an adverse reaction that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisa-tion, results in persistent or significant disability or incapacity, or is a birth defect32) 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.
• Inability or unwillingness to provide written informed consent, either independently or with the assistance of a proxy.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Statin continued; Patients in which the statin was continued after the index event	Drug: Statin; Statin use; Other Names: atorvastatin, rosuvastatin, pravastatin, simvastatin, fluvastatin
Statin discontinued; Patients in which the statin was discontinued after the index event

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-Related Quality of Life (HrQoL)	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. months.	3, 6, 12, 18, 24 (and 36) months
Major Adverse Cardiovascular Events (MACE) free survival	Classical 3-point MACE (cardiovascular death, nonfatal MI, or nonfatal stroke) and non-cardiovascular death. Measurements at 3, 6, 12, 18, 24 (and 36) months.	3, 6, 12, 18, 24 (and 36) months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional outcome	This will be assessed using the modified Rankin Scale (mRS), with scores ranging from 0 to 6 (lower scores indicating better function).	3, 6, 12, 18, 24 months
Cognition	This will be measured using the Montreal Cognitive Assessment (MoCA) with scores ranging from 0 (worst) to 30 (best) or the Telephone version of the MoCA (TMoCA) with scores ranging from 0 (worst) to 22 (best)	3, 6, 12, 18, 24 months
Number of falls	Falls, measured using the falls calender. Participant returns the fall calender every 3 months.	3, 6, 12, 18, 24 months
Time to first fall	Falls, measured using the falls calender. Participant returns the fall calender every 3 months.	3, 6, 12, 18, 24 months
General quality of life using the EQ-5D-5L	General QoL, measured by the EuroQol Questionnaire (EQ-5D-5L), with scores ranging from 0-100, the higher, the better.	3, 6, 12, 18, 24 months
Societal costs	Societal costs measured by The Older Persons and Informal Caregivers Survey - Minimum Data Set (TOPICS-MDS) (questions 23 - 37)	3, 6, 12, 18, 24 months
Cardiovascular risk status	This will be assessed by collecting vital signs (height, weight, and blood pressure) and lipid levels. The exact way how to combine these factors into one risk status will be determined.	3, 6, 12, 18, 24 months

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: VU University of Amsterdam
• Investigators: Principal Investigator: Renske van den Berg-Vos, Prof. dr., Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Principal Investigator: Nathalie van der Velde, Prof. dr., Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: July 3, 2024
• First Submitted That Met QC Criteria: January 19, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 19, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Ischemic Stroke; Stroke; Cerebral Infarction; Ischemic Attack, Transient; Ischemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium; Simvastatin; Pravastatin
• Other Study ID Numbers: 2024.0202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The SAFEST database can be requested by other researchers. These requests will be reviewed according the requirements for sharing SAFEST data.
• IPD Sharing Time Frame: After data-collection/analysis.

IPD Sharing Access Criteria

Requirements for sharing SAFEST data include:

• privacy laws of the Netherlands, policy of NFU and AmsterdamUMC must be followed
• data will be anonymously shared
• data can only be used to study the research question for which participants signed the ICF
• data will not be shared for commercial purposes.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No