No difference in muscle symptoms with statin compared to placebo in n-of-1 trials
Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials
Introduction and methods
Although safety of statins has been confirmed in systematic reviews and meta-analyses of RCTs, there is doubt on less severe muscle symptoms of statin therapy. Unblinded observational studies and media reports may lead to people believing that statins cause muscle pain and discontinuation of treatment [1-7].
Blinded n-of-1 trials with individual patients may help in reliably determining whether muscle symptoms are caused by statins . N-of-1 trials are randomized trials in individual patients and the overall effect can be examined by combining a number of n-of-1 trials in an analysis.
This study (StatinWISE, Statin Web-based Investigation of Side Effects) examined the effect of statins on all muscle symptoms and on muscle symptoms perceived to be related to statins by comparing treatment periods of statins and placebo in people who had previously reported muscle symptoms on statins.
StatinWISE was a series of randomized, double blind, placebo controlled n-of-1 trials. Length of the trial was one year for each individual and consisted of six two month treatment periods (three of placebo and three of atorvastatin) in a random order. Recruited patients were considering stopping statin therapy or had stopped statin in the last three years because of muscle symptoms. Primary outcome was self-reported muscle symptoms, measured each day with a validated visual analogue scale for the last 7 days of each treatment period. A secondary outcome was (intention to) restart of treatment with statins, assessed three months after the end of the final treatment period. 151 Participants were included in the primary analysis.
- There was no difference in mean muscle symptoms score between the statin and placebo periods (mean difference statin minus placebo -0.11, 95%CI: -0.36 to 0.14, P=0.40).
- There was no effect of statins on the occurrence of muscle symptoms overall (OR 1.11, 95%CI: 0.62-1.99) or for muscle symptoms that could not be attributed to another cause (OR 1.22, 95%CI: 0.77 to 1.94).
- During an end of trial discussion, participants received their results and 88% said the trial had been helpful and 66% reported that they had already or intended to resume taking statins.
- There was no evidence of a difference in probability of withdrawals during a statin period compared with a placebo period, overall (RR 0.87, 95%CI: 0.55-1.38, P=0.56) or because of intolerable muscle symptoms (RR 1.38, 95%CI: 0.66-2.83, P=0.56).
This analysis of n-of-1 trials with 151 participants, who had previously reported severe muscle symptoms when taking statins, demonstrated that there was no difference in muscle symptoms when participants were on a statin compared to when they were taking placebo. After completing the trial, 66% of participants responded that they started or intended to start treatment with statins. The authors state: “The availability of n-of-1 trial packs in clinical care would allow patients and clinician to replicate this study in individuals, for any statin and at any dose to suit clinical needs, in primary care or in lipid clinics.“