Statin myopathy: A common dilemma not reflected in clinical trials

Abstract

Although statins are remarkably effective, they are still underprescribed because of concerns about muscle toxicity. We review the aspects of statin myopathy that are important to the primary care physician and provide a guide for evaluating patients on statins who present with muscle complaints. We outline the differential diagnosis, the risks and benefits of statin therapy in patients with possible toxicity, and the subsequent treatment options.

Interpretation of the evidence for the efficacy and safety of statin therapy

“…20,21 Robustness for detecting real treatment effects It has been suggested that ascertainment of adverse events in randomized trials may not be sufficiently specific or sensitive to detect adverse effects of treatment reliably. 11,12,[22][23][24] However, comparisons within randomized trials with unbiased ascertainment of outcomes between the treatment groups are robust against both over-and under-ascertainment. 25 For example, if the study treatment produced a 20% proportional decrease (or increase) in the rate of an outcome that occurred in 10% of control patients, then (as shown in Table 1) the ability to detect such an effect in a randomized trial of 20,000 patients would not be much altered by the random addition of reported events that were not actually the outcome of interest (i.e.…”

“…It has been suggested that, because of the exclusion criteria in randomized trials, results from observational studies based on use of a treatment in routine practice (sometimes referred to, misleadingly, as "real world" evidence 10,22,24,59 ) are more widely generalizable about its effects. 11,22,24,60,61 However, meta-analyses of randomized trials with different eligibility criteria that have included large numbers of different types of patient (e.g.…”

“…11,22,24,60,61 However, meta-analyses of randomized trials with different eligibility criteria that have included large numbers of different types of patient (e.g. although some statin trials excluded people who were older or who had particular conditions, other statin trials did not) may be able to address this putative limitation by yielding unbiased information based on sufficient numbers of individuals with different characteristics that can then be widely generalized (for example, with the statin trials, [31][32][33]62 older and younger people, women and men, individuals with and without pre-existing vascular disease or other conditions).…”

“…so-called "statin-intolerant" patients). 11,12,[22][23][24]61,[70][71][72][73] However, for treatments that are not yet on the market or that have not yet been widely adopted into routine practice (as was the case during the recruitment phase of many of the large clinical outcome trials of statins 62,74 ), few patients will have previously been exposed to the treatment and excluded because of having had problems with it.…”

“…11,12,[22][23][24]72,245 However, as is discussed above, few patients would have been exposed to statin therapy prior to recruitment into many of the large clinical outcome trials and use of a pre-randomization placebo "run-in" phase in about half of the trials (see webtable) would tend to increase the sensitivity of the subsequent randomized comparisons to detect any effects. 75 The inclusion of large numbers of different types of patient in different randomized trials with different eligibility criteria also makes the evidence about any side-effects of statin therapy far more widely generalizable 63 to routine practice than is often asserted.…”