Side effects

Adverse effects of statins are uncommon but include liver enzyme elevations and myositis or rhabdomyolysis. These are more common in older patients, those with multiple diseases, and those on multiple drugs.

The incidence of statin myopathy is dose-dependent and may present as diffuse myalgias or otherwise unexplainable muscle tenderness or weakness with reversal upon medication discontinuation.

The most commonly reported adverse effect of statins is myalgia. This is characterised by muscle and tendon pain, stiffness, muscle weakness and cramping and in observational trials appears to affects 10-15% of patients taking statins. However, this observation is compounded by the fact that muscle aches and pains are common in the general population, especially with increasing age, and recent research suggests that, in many cases, these may not be directly. When this is studies in randomised controlled trials, in which patients are blind to whether they are taking statin or placebo, there seems to be little or no increase in muscle symptoms between statin and placebo groups. (1)

The StatinWISE trial investigated the effect of statins on muscle symptoms in people who had stopped, or were considering stopping, statins due to reported muscle symptoms. Participants were given atorvastatin, then placebo, in sequence and were blind to which they were taking. The trial conclusion was that there was no difference in self-reported muscle symptoms when taking atorvastatin, compared to placebo. (2)

There is some evidence that statin therapy is also associated with an increased risk of developing new-onset diabetes mellitus (3) although one large trial of rosuvastatin showed that while statin therapy increased the risk of diabetes mellitus, this hazard was exceeded by the cardiovascular benefits of statins, with 134 vascular events or deaths avoided for every 54 new cases of diabetes diagnosed. (4)

Reference

1. Collaboration for authored content; Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. Lancet. 2022 Sep
2. Herrett E, Williamson E, Brack K, et al; Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials. BMJ. 2021 Feb 24;372:n135
3. Collins R et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016 Nov 19;388(10059):2532-2561
4. Ridker PM, Pradhan A, MacFadyen JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012 Aug 11;380(9841):565-71.