Clinical trial NCT06785740: Statins in Frail Older Patients with Ischemic Stroke or Transient Ischemic Attack - the Prospective Cohort Study
Official title: StAtins in Frail OldEr Patients with Ischemic Stroke or Transient Ischemic Attack - the Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ischemic Stroke
TIA
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: VU University of Amsterdam
First posted: 2025-01-21
Enrollment: 300
Sex: ALL
Minimum age (years): 70
Maximum age (years): 120
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: frail individuals aged 70 and above with a recent ischemic stroke or transient ischemic attack (TIA)

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Health-Related Quality of Life (HrQoL)
timeFrame: 3, 6, 12, 18, 24 (and 36) months
measure: Major Adverse Cardiovascular Events (MACE) free survival
timeFrame: 3, 6, 12, 18, 24 (and 36) months
Secondary outcomes:
measure: Functional outcome
timeFrame: 3, 6, 12, 18, 24 months
measure: Cognition
timeFrame: 3, 6, 12, 18, 24 months
measure: Number of falls
timeFrame: 3, 6, 12, 18, 24 months
measure: Time to first fall
timeFrame: 3, 6, 12, 18, 24 months
measure: General quality of life using the EQ-5D-5L
timeFrame: 3, 6, 12, 18, 24 months
measure: Societal costs
timeFrame: 3, 6, 12, 18, 24 months
measure: Cardiovascular risk status
timeFrame: 3, 6, 12, 18, 24 months
Other outcomes:
Locations:
city: Almere
country: Netherlands
facility: Flevoziekenhuis
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location AMC
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Zwolle
country: Netherlands
facility: Isala Klinieken
Study officials:
affiliation: Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
name: Renske van den Berg-Vos, Prof. dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
name: Nathalie van der Velde, Prof. dr.
role: PRINCIPAL_INVESTIGATOR
References: