The effect of statins on muscle symptoms in primary care: the StatinWISE series of 200 N-of-1 RCTs

Uncertainty persists about whether or not statins cause symptomatic muscle adverse effects (e.g. pain, stiffness and weakness) in the absence of severe myositis. To establish the effect of statins on all muscle symptoms, and the effect of statins on muscle symptoms that are perceived to be statin re...

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Vydáno v:Health technology assessment (Winchester, England) Ročník 25; číslo 16; s. 1 - 62
Hlavní autoři: Herrett, Emily, Williamson, Elizabeth, Brack, Kieran, Perkins, Alexander, Thayne, Andrew, Shakur-Still, Haleema, Roberts, Ian, Prowse, Danielle, Beaumont, Danielle, Jamal, Zahra, Goldacre, Ben, van Staa, Tjeerd, MacDonald, Thomas M, Armitage, Jane, Moore, Michael, Hoffman, Maurice, Smeeth, Liam
Médium: Journal Article
Jazyk:angličtina
Vydáno: England NIHR Journals Library 01.03.2021
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ISSN:1366-5278, 2046-4924, 2046-4924
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Abstract Uncertainty persists about whether or not statins cause symptomatic muscle adverse effects (e.g. pain, stiffness and weakness) in the absence of severe myositis. To establish the effect of statins on all muscle symptoms, and the effect of statins on muscle symptoms that are perceived to be statin related. A series of 200 double-blinded N-of-1 trials. Participants were recruited from 50 general practices in England and Wales. Patients who were considering discontinuing statin use and those who had discontinued statin use in the last 3 years because of perceived muscle symptoms. Participants were randomised to a sequence of six 2-month treatment periods during which they received 20 mg of atorvastatin daily or a matched placebo. The primary outcome was self-reported muscle symptoms rated using a visual analogue scale on the last week of each treatment period. Secondary outcomes included the participant's belief about the cause of their muscle symptoms, the site of muscle symptoms, how the muscle symptoms affected the participant, any other symptoms they experienced, adherence to medication, the participant's decision about statin treatment following the trial, and whether or not they found their own trial result helpful. A total of 151 out of 200 (75.5%) randomised participants provided one or more visual analogue scale measurements in a placebo period and one or more measurements in a statin period, and were included in the primary analysis. There was no evidence of a difference in muscle symptom scores between statin and placebo periods (mean difference statin minus placebo -0.11, 95% confidence interval -0.36 to 0.14;  = 0.398). Withdrawals, adherence and missing data were similar during the statin periods and the placebo periods. Among people who previously reported severe muscle symptoms while taking statins, this series of randomised N-of-1 trials found no overall effect of statins on muscle symptoms compared with the placebo. The slight difference in withdrawals due to muscle symptoms suggests that statins may contribute to symptoms in a small number of patients. The results are generalisable to patients who are considering discontinuing or have already discontinued statins because of muscle symptoms, and who are willing to re-challenge or participate in their own N-of-1 trial. We recommend that additional statins and doses are explored using N-of-1 trials. More broadly, N-of-1 trials present a useful tool for exploring transient symptoms with other medications. This study used 20-mg doses of atorvastatin only. Furthermore, a dropout rate of 43% was observed, but this was accounted for in the power calculations. Current Controlled Trials ISRCTN30952488 and EudraCT 2016-000141-31. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 16. See the NIHR Journals Library website for further project information.
AbstractList Statins are one of the most commonly prescribed drugs in the UK. There is strong evidence that they are effective in safely reducing heart disease; however, there is some doubt about whether or not statins cause muscle pain, stiffness or weakness. This research has been carried out to understand the effect of statins on muscle symptoms. To answer our question, we asked 200 volunteers from across England and Wales to participate in the study. Patients who joined the study either had recently stopped taking statins because of muscle symptoms or were considering stopping because of muscle symptoms. Patients who participated were randomly assigned to a sequence of six 2-month treatment periods during which they received either statins or a placebo. Neither patients nor their general practitioner knew which tablet they were receiving. This helped to reduce bias in the data. At the end of each treatment period, patients were asked to report any muscle symptoms, or any other symptoms, that they experienced. The key result of this work is that patients reported no difference, on average, in their muscle symptoms between periods of taking a statin and periods of taking a placebo. We also assessed the impact on the patient’s quality of life by looking at how statins affected the following areas: general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life. As with muscle symptoms, there was no evidence of a difference between statin and placebo periods. The majority of patients who finished the trial decided to continue using statins after the trial. Future research should be carried out to assess different statin doses, as higher doses are often used following a heart attack. In addition, further work is needed to see how the approach we used could be adopted into everyday clinical care.
Uncertainty persists about whether or not statins cause symptomatic muscle adverse effects (e.g. pain, stiffness and weakness) in the absence of severe myositis.BACKGROUNDUncertainty persists about whether or not statins cause symptomatic muscle adverse effects (e.g. pain, stiffness and weakness) in the absence of severe myositis.To establish the effect of statins on all muscle symptoms, and the effect of statins on muscle symptoms that are perceived to be statin related.OBJECTIVESTo establish the effect of statins on all muscle symptoms, and the effect of statins on muscle symptoms that are perceived to be statin related.A series of 200 double-blinded N-of-1 trials.DESIGNA series of 200 double-blinded N-of-1 trials.Participants were recruited from 50 general practices in England and Wales.SETTINGParticipants were recruited from 50 general practices in England and Wales.Patients who were considering discontinuing statin use and those who had discontinued statin use in the last 3 years because of perceived muscle symptoms.PARTICIPANTSPatients who were considering discontinuing statin use and those who had discontinued statin use in the last 3 years because of perceived muscle symptoms.Participants were randomised to a sequence of six 2-month treatment periods during which they received 20 mg of atorvastatin daily or a matched placebo.INTERVENTIONSParticipants were randomised to a sequence of six 2-month treatment periods during which they received 20 mg of atorvastatin daily or a matched placebo.The primary outcome was self-reported muscle symptoms rated using a visual analogue scale on the last week of each treatment period. Secondary outcomes included the participant's belief about the cause of their muscle symptoms, the site of muscle symptoms, how the muscle symptoms affected the participant, any other symptoms they experienced, adherence to medication, the participant's decision about statin treatment following the trial, and whether or not they found their own trial result helpful.MAIN OUTCOME MEASURESThe primary outcome was self-reported muscle symptoms rated using a visual analogue scale on the last week of each treatment period. Secondary outcomes included the participant's belief about the cause of their muscle symptoms, the site of muscle symptoms, how the muscle symptoms affected the participant, any other symptoms they experienced, adherence to medication, the participant's decision about statin treatment following the trial, and whether or not they found their own trial result helpful.A total of 151 out of 200 (75.5%) randomised participants provided one or more visual analogue scale measurements in a placebo period and one or more measurements in a statin period, and were included in the primary analysis. There was no evidence of a difference in muscle symptom scores between statin and placebo periods (mean difference statin minus placebo -0.11, 95% confidence interval -0.36 to 0.14; p = 0.398). Withdrawals, adherence and missing data were similar during the statin periods and the placebo periods.RESULTSA total of 151 out of 200 (75.5%) randomised participants provided one or more visual analogue scale measurements in a placebo period and one or more measurements in a statin period, and were included in the primary analysis. There was no evidence of a difference in muscle symptom scores between statin and placebo periods (mean difference statin minus placebo -0.11, 95% confidence interval -0.36 to 0.14; p = 0.398). Withdrawals, adherence and missing data were similar during the statin periods and the placebo periods.Among people who previously reported severe muscle symptoms while taking statins, this series of randomised N-of-1 trials found no overall effect of statins on muscle symptoms compared with the placebo. The slight difference in withdrawals due to muscle symptoms suggests that statins may contribute to symptoms in a small number of patients. The results are generalisable to patients who are considering discontinuing or have already discontinued statins because of muscle symptoms, and who are willing to re-challenge or participate in their own N-of-1 trial.CONCLUSIONSAmong people who previously reported severe muscle symptoms while taking statins, this series of randomised N-of-1 trials found no overall effect of statins on muscle symptoms compared with the placebo. The slight difference in withdrawals due to muscle symptoms suggests that statins may contribute to symptoms in a small number of patients. The results are generalisable to patients who are considering discontinuing or have already discontinued statins because of muscle symptoms, and who are willing to re-challenge or participate in their own N-of-1 trial.We recommend that additional statins and doses are explored using N-of-1 trials. More broadly, N-of-1 trials present a useful tool for exploring transient symptoms with other medications.FUTURE WORKWe recommend that additional statins and doses are explored using N-of-1 trials. More broadly, N-of-1 trials present a useful tool for exploring transient symptoms with other medications.This study used 20-mg doses of atorvastatin only. Furthermore, a dropout rate of 43% was observed, but this was accounted for in the power calculations.LIMITATIONSThis study used 20-mg doses of atorvastatin only. Furthermore, a dropout rate of 43% was observed, but this was accounted for in the power calculations.Current Controlled Trials ISRCTN30952488 and EudraCT 2016-000141-31.TRIAL REGISTRATIONCurrent Controlled Trials ISRCTN30952488 and EudraCT 2016-000141-31.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 16. See the NIHR Journals Library website for further project information.FUNDINGThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 16. See the NIHR Journals Library website for further project information.
Uncertainty persists about whether or not statins cause symptomatic muscle adverse effects (e.g. pain, stiffness and weakness) in the absence of severe myositis. To establish the effect of statins on all muscle symptoms, and the effect of statins on muscle symptoms that are perceived to be statin related. A series of 200 double-blinded N-of-1 trials. Participants were recruited from 50 general practices in England and Wales. Patients who were considering discontinuing statin use and those who had discontinued statin use in the last 3 years because of perceived muscle symptoms. Participants were randomised to a sequence of six 2-month treatment periods during which they received 20 mg of atorvastatin daily or a matched placebo. The primary outcome was self-reported muscle symptoms rated using a visual analogue scale on the last week of each treatment period. Secondary outcomes included the participant's belief about the cause of their muscle symptoms, the site of muscle symptoms, how the muscle symptoms affected the participant, any other symptoms they experienced, adherence to medication, the participant's decision about statin treatment following the trial, and whether or not they found their own trial result helpful. A total of 151 out of 200 (75.5%) randomised participants provided one or more visual analogue scale measurements in a placebo period and one or more measurements in a statin period, and were included in the primary analysis. There was no evidence of a difference in muscle symptom scores between statin and placebo periods (mean difference statin minus placebo -0.11, 95% confidence interval -0.36 to 0.14;  = 0.398). Withdrawals, adherence and missing data were similar during the statin periods and the placebo periods. Among people who previously reported severe muscle symptoms while taking statins, this series of randomised N-of-1 trials found no overall effect of statins on muscle symptoms compared with the placebo. The slight difference in withdrawals due to muscle symptoms suggests that statins may contribute to symptoms in a small number of patients. The results are generalisable to patients who are considering discontinuing or have already discontinued statins because of muscle symptoms, and who are willing to re-challenge or participate in their own N-of-1 trial. We recommend that additional statins and doses are explored using N-of-1 trials. More broadly, N-of-1 trials present a useful tool for exploring transient symptoms with other medications. This study used 20-mg doses of atorvastatin only. Furthermore, a dropout rate of 43% was observed, but this was accounted for in the power calculations. Current Controlled Trials ISRCTN30952488 and EudraCT 2016-000141-31. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 16. See the NIHR Journals Library website for further project information.
Background: Uncertainty persists about whether or not statins cause symptomatic muscle adverse effects (e.g. pain, stiffness and weakness) in the absence of severe myositis. Objectives: To establish the effect of statins on all muscle symptoms, and the effect of statins on muscle symptoms that are perceived to be statin related. Design: A series of 200 double-blinded N-of-1 trials. Setting: Participants were recruited from 50 general practices in England and Wales. Participants: Patients who were considering discontinuing statin use and those who had discontinued statin use in the last 3 years because of perceived muscle symptoms. Interventions: Participants were randomised to a sequence of six 2-month treatment periods during which they received 20 mg of atorvastatin daily or a matched placebo. Main outcome measures: The primary outcome was self-reported muscle symptoms rated using a visual analogue scale on the last week of each treatment period. Secondary outcomes included the participant’s belief about the cause of their muscle symptoms, the site of muscle symptoms, how the muscle symptoms affected the participant, any other symptoms they experienced, adherence to medication, the participant’s decision about statin treatment following the trial, and whether or not they found their own trial result helpful. Results: A total of 151 out of 200 (75.5%) randomised participants provided one or more visual analogue scale measurements in a placebo period and one or more measurements in a statin period, and were included in the primary analysis. There was no evidence of a difference in muscle symptom scores between statin and placebo periods (mean difference statin minus placebo –0.11, 95% confidence interval –0.36 to 0.14; p = 0.398). Withdrawals, adherence and missing data were similar during the statin periods and the placebo periods. Conclusions: Among people who previously reported severe muscle symptoms while taking statins, this series of randomised N-of-1 trials found no overall effect of statins on muscle symptoms compared with the placebo. The slight difference in withdrawals due to muscle symptoms suggests that statins may contribute to symptoms in a small number of patients. The results are generalisable to patients who are considering discontinuing or have already discontinued statins because of muscle symptoms, and who are willing to re-challenge or participate in their own N-of-1 trial. Future work: We recommend that additional statins and doses are explored using N-of-1 trials. More broadly, N-of-1 trials present a useful tool for exploring transient symptoms with other medications. Limitations: This study used 20-mg doses of atorvastatin only. Furthermore, a dropout rate of 43% was observed, but this was accounted for in the power calculations. Trial registration: Current Controlled Trials ISRCTN30952488 and EudraCT 2016-000141-31. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 16. See the NIHR Journals Library website for further project information.
Author Williamson, Elizabeth
Prowse, Danielle
Armitage, Jane
Beaumont, Danielle
Herrett, Emily
Goldacre, Ben
van Staa, Tjeerd
Moore, Michael
Shakur-Still, Haleema
MacDonald, Thomas M
Perkins, Alexander
Roberts, Ian
Smeeth, Liam
Jamal, Zahra
Hoffman, Maurice
Thayne, Andrew
Brack, Kieran
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Issue 16
Keywords CHOLESTEROL
CARDIOVASCULAR DISEASES
PRIMARY HEALTH CARE
VISUAL ANALOGUE SCALE
GENERAL PRACTITIONERS
MEDICATION ADHERENCE
MUSCLE PAIN
SECONDARY PREVENTION
ATORVASTATIN
Language English
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Snippet Uncertainty persists about whether or not statins cause symptomatic muscle adverse effects (e.g. pain, stiffness and weakness) in the absence of severe...
Statins are one of the most commonly prescribed drugs in the UK. There is strong evidence that they are effective in safely reducing heart disease; however,...
Background: Uncertainty persists about whether or not statins cause symptomatic muscle adverse effects (e.g. pain, stiffness and weakness) in the absence of...
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StartPage 1
SubjectTerms atorvastatin
cardiovascular diseases
cholesterol
Cost-Benefit Analysis
England - epidemiology
general practitioners
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects
medication adherence
muscle pain
Muscles
Primary Health Care
secondary prevention
Technology Assessment, Biomedical
visual analogue scale
Title The effect of statins on muscle symptoms in primary care: the StatinWISE series of 200 N-of-1 RCTs
URI https://www.ncbi.nlm.nih.gov/pubmed/33709907
https://www.proquest.com/docview/2501257392
https://pubmed.ncbi.nlm.nih.gov/PMC8020196
https://doaj.org/article/a926cd9d5534496884c8c3df2c72af96
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