Authors' objectives: Background: Statins are drugs that lower cholesterol and reduce the risk of heart attacks and strokes. They are the most commonly prescribed treatment in the UK. Recently, updated NICE recommendations increased the number of people eligible to receive statins by over 2 million. Statins are known to cause very rare but serious side effects such as rhabdomyolysis (breakdown of muscle tissue) and its milder form called myopathy. Many patients stop taking statins due to less severe symptoms, such as muscle pain or fatigue. When investigating these less severe symptoms, trials have not found any differences in the numbers of people reporting them between those taking statins and those taking placebo. However, perhaps because people are warned about risk of the rare muscle breakdown, many patients believe that statins cause their muscle symptoms. Given the known effectiveness of statins in reducing heart disease and strokes, accurate data on the cause of symptoms experienced during statin use are needed to inform patients and doctors treatment choices. The proposed study will address this important uncertainty about statin therapy for patients and the population. Aim: To determine whether symptoms occurring during statin use are caused by statins. Methods: We propose a trial investigating side effects of statins compared to a matching placebo. We will include 200 participants who have recently stopped or wish to stop taking statins due to unwanted symptoms. Each participant will be in the study for one year, split into six two-month treatment periods. In each period, the participant will be randomly allocated to take statins or matching placebo. This is called an N-of-1 trial. Two months is sufficient for short-term side effects to emerge, and the trial s one year duration is brief enough to minimise any adverse impact on cardiovascular outcomes from under-treatment. Participants will be asked to submit outcome data for one week at the end of each treatment period using a specially-designed mobile application or pen and paper diaries. Outcomes will be self-reported symptoms using a visual sliding 0-100 scale for muscle pain, weakness, tenderness, stiffness or cramps linked to statins. A questionnaire will explore symptoms in more detail. Non-responders will be prompted by email, text, post or phone. GPs will report serious adverse events to the study team. Participants will be recruited through general practices. At the end of their 12 month follow-up, participants will be shown summaries of their individual results by their General Practitioner (GP) or trial nurse, which will help them to decide whether to continue taking statins. We will also combine the results from each participant to perform an analysis and formally assess the extent to which statins cause muscle symptoms at the population level. Patient and public involvement: a panel of patients and the public will be convened to advise on preparation of study documentation and ensure that patient needs are met during the main study phase. Dissemination: The results of this study will be published in scientific journals and will be presented to patient and GP groups at formal meetings and in written reports. We will use social media and will target medical correspondents of newspapers and magazines, in this country and overseas, to draw attention to our results.

Project Status: Completed

URL for project: http://www.nets.nihr.ac.uk/projects/hta/1449159

Year Published: 2021

URL for published report: https://www.journalslibrary.nihr.ac.uk/programmes/hta/1449159#/

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England, United Kingdom

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk

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