StAtins in Frail oldEr patients with ischemic Stroke or Transient ischemic attack

The primary objective of the study titled "StAtins in Frail oldEr patients with ischemic Stroke or Transient ischemic attack" (SAFEST) is to evaluate whether **daily functioning** and **health-related quality of life** are improved at two years when statins are discontinued or not initiated, compared to when statins are used, in frail patients aged 70 years or older who have experienced a recent **ischemic stroke** or **transient ischemic attack**. This objective is clinically relevant as it addresses the potential impact of statin therapy on the quality of life and functional outcomes in an elderly, frail population, which is crucial for optimizing treatment strategies in this demographic.

The clinical trial involves participants who have experienced an **ischemic stroke** or transient ischemic attack. The study population consists of both male and female subjects aged 70 years or older. Participants are required to have been diagnosed with ischemic stroke or transient ischemic attack within the past six weeks and must exhibit frailty, as indicated by a pre-event score of 4-7 and/or a post-event score of 6-7 on the validated Clinical Frailty Scale. The trial does not specifically target a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. The selection criteria focus on age, recent medical history, and frailty status, ensuring that the study population is representative of older adults with recent cerebrovascular events.

The clinical trial is designed to evaluate the impact of discontinuing or not initiating **statins** on daily functioning and health-related quality of life in frail patients aged 70 years or older who have experienced a recent **ischemic stroke** or **transient ischemic attack**. This study employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The trial is expected to span over a period of five years, with an estimated recruitment start date of February 15, 2023, and an anticipated end date of August 15, 2028.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, recent diagnosis of ischemic stroke or transient ischemic attack, and frailty as defined by the Clinical Frailty Scale. Following the screening, participants will be randomly assigned to either continue or discontinue statin therapy. Follow-up visits will be conducted at regular intervals to monitor daily functioning and health-related quality of life, with primary endpoints assessed at two years using the Older Persons and Informal Caregivers Survey Short Form (TOPICS-SF) and the PROMIS-10. Secondary endpoints, including physical functioning, cognition, and cardiovascular risk status, will be evaluated at one and two years.

The expected length of participant involvement is up to two years, with conditions for early termination including withdrawal of consent, adverse events, or any significant protocol deviations. The trial is categorized as a low-intervention study, as it evaluates current care strategies without introducing new investigational products. The study aims to provide valuable insights into the management of statin therapy in older, frail patients with a history of ischemic stroke or transient ischemic attack, contributing to evidence-based clinical decision-making.

The clinical trial involves the administration of **Atorvastatin**, marketed under the name "Atorvastatine Accord 10 mg filmomhulde tabletten." This experimental medication is presented in the form of a **film-coated tablet**. Each tablet contains 10 mg of the active substance **atorvastatin**, which is a chemical compound. The route of administration for this medication is **oral**, and it is to be taken once daily. The maximum daily dose is 10 mg, and the treatment period is limited to one month. The medication is manufactured by Accord Healthcare B.V. and is authorized for use in the Netherlands under the marketing authorization number RVG 118716.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of atorvastatin to assess its impact on daily functioning and health-related quality of life in frail patients aged 70 years or older who have experienced a recent ischemic stroke or transient ischemic attack. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

Efficacy in the clinical trial titled "StAtins in Frail oldEr patients with ischemic Stroke or Transient ischemic attack" will be assessed through both primary and secondary endpoints. The primary endpoints include the evaluation of daily functioning and health-related quality of life (hrQoL) at two years. Daily functioning will be measured using The Older Persons and Informal Caregivers Survey Short Form (TOPICS-SF), while hrQoL will be assessed with the PROMIS-10, which provides global mental health and global physical health summary scores.

Secondary endpoints will be evaluated at one and two years and include daily functioning and hrQoL, as well as additional measures such as physical functioning, functional outcome, cognition, emotional problems, falls, adverse drug events, cardiovascular risk status (based on clinical tests and laboratory results), general quality of life, societal costs, incidence of cardiovascular event recurrences, and mortality. These assessments will provide a comprehensive evaluation of the impact of discontinuing or not initiating statin therapy compared to its continued use in frail patients aged 70 years or older who have experienced a recent ischemic stroke or transient ischemic attack.