Statins for extension of disability-free survival and primary prevention of cardiovascular events among older people: protocol for a randomised controlled trial in primary care (STAREE trial).

INTRODUCTION: The world is undergoing a demographic transition to an older population. Preventive healthcare has reduced the burden of chronic illness at younger ages but there is limited evidence that these advances can improve health at older ages. Statins are one class of drug with the potential to prevent or delay the onset of several causes of incapacity in older age, particularly major cardiovascular disease (CVD). This paper presents the protocol for the STAtins in Reducing Events in the Elderly (STAREE) trial, a randomised double-blind placebo-controlled trial examining the effects of statins in community dwelling older people without CVD, diabetes or dementia. METHODS AND ANALYSIS: We will conduct a double-blind, randomised placebo-controlled trial among people aged 70 years and over, recruited through Australian general practice and with no history of clinical CVD, diabetes or dementia. Participants will be randomly assigned to oral atorvastatin (40 mg daily) or matching placebo (1:1 ratio). The co-primary endpoints are disability-free survival defined as survival-free of dementia and persistent physical disability, and major cardiovascular events (cardiovascular death or non-fatal myocardial infarction or stroke). Secondary endpoints are all-cause death, dementia and other cognitive decline, persistent physical disability, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, heart failure, atrial fibrillation, fatal and non-fatal cancer, all-cause hospitalisation, need for permanent residential care and quality of life. Comparisons between assigned treatment arms will be on an intention-to-treat basis with each of the co-primary endpoints analysed separately in time-to-first-event analyses using Cox proportional hazards regression models. ETHICS AND DISSEMINATION: STAREE will address uncertainties about the preventive effects of statins on a range of clinical outcomes important to older people. Institutional ethics approval has been obtained. All research outputs will be disseminated to general practitioner co-investigators and participants, published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT02099123.

Older participant perspectives on permanent study drug discontinuation in an ongoing primary prevention trial of statins.

PURPOSE: Study drug discontinuation is commonplace in clinical trials of older populations. Little is known about why older participants discontinue the study drug. This qualitative study aimed to understand factors contributing to permanent study drug discontinuation among participants aged ≥ 70 years within an ongoing primary prevention trial of statins by exploring their experiences and perceptions. METHODS: Trial participants who had permanently discontinued the study drug within 2 years of randomisation were purposively sampled by age (< 75 and ≥ 75 years) and sex to participate in semi-structured phone interviews between March 2019 and February 2020. Interviews were audio-recorded, transcribed and analysed thematically. RESULTS: Thirty participants were interviewed (21 females; mean age, 77 years), and three themes were identified from the data. Perceived adverse events (AEs) and their effect on daily living (mobility, functional capacity, quality of life) were identified as the major factors leading to the participants permanently discontinuing their study drug, despite an ambiguity about the cause of the AE. For some, concurrent challenging life circumstances further lowered their tolerance to perceived AEs thus making discontinuation more likely. A few discontinuations were attributed to other factors (e.g. GP advice, unrelated illness). CONCLUSION: Among healthy older participants enrolled in a statin trial, perceived AEs and their related impact were key factors contributing to the permanent study drug discontinuation. Addressing anticipated participant-reported AEs and their concerns about drug-related side effects at trial entry, as well as offering timely medical assistance and support when AEs occur, may be useful to reduce drug discontinuation rates.