Many patients suffer from myalgias during statin therapy and therefore discontinue the treatment. The now published StatinWISE study shows that these complaints are not usually caused by the statin itself, but possibly by a nocebo effect.
Statins are considered to be one of the most effective and safest drugs for fighting cardiovascular diseases. They inhibit cholesterol production and indirectly increase low-density lipoprotein (LDL) receptors on hepatocytes, thereby lowering LDL cholesterol.
However, they have a bad image among many patients. This is because they are suspected of causing muscle pain. While it has been proven that statins can indeed lead to severe myopathies and rhabdomyolysis, only a tiny percentage of patients are actually affected (about 1 in 10,000). In the vast majority of patients with statin-associated muscle symptoms (SAMS), on the other hand, many researchers assume a so-called nocebo effect. This means that the mere expectation that myalgia will occur during statin therapy leads to myalgia. So far, studies have painted a mixed picture: In some observational studies, statins were associated with more SAMS, but many randomised control trials (RCTs) found no such effect. Now a new, well-designed RCT has been published in the British Medical Journal that confirms previous RCTs.
The "StatinWISE" study included a total of 200 patients from England and Wales who were either thinking about stopping their statin therapy because of muscle symptoms (1/4 of the patients) or who had already stopped (3/4 of the patients). The mean age of the subjects was 69 years, 58% were male, 17% had diabetes and 70% had a history of cardiovascular disease. The mean baseline cholesterol level was 5.3 mmol/l or 205 mg/dl.
All patients were willing to take a statin again for the duration of the study. Exclusion criteria were a history of elevated creatine kinase (min. 5-fold increase) or elevated transaminases (min. 3-fold increase), "persistent, generalised, unexplained muscle pain" or a contraindication to atorvastatin 20 mg.
The study duration was one year and was divided into six 2-month periods. In each arm, patients received either a placebo or atorvastatin 20 mg. The sequences of statin and placebo phases were randomly determined for each patient from 8 pre-generated sequences, e.g. statin - placebo - placebo - statin - placebo - statin. In total, statin and placebo were taken by each patient for 6 months. In the last 7 days of each section, the patients then documented their muscle discomfort daily on a visual analogue scale (0 = no discomfort, 10 = maximum discomfort). The following items were included: pain, weakness, tenderness, stiffness, spasm. An average muscle symptom score was then calculated for each patient.
Of the 200 patients included, 151 (76%) completed at least one visual analogue scale in each of the placebo and statin sections and were included in the analysis. Surprisingly, the muscle symptom score was slightly lower on statin therapy than on placebo (1.68 versus 2.57). But this difference was not statistically significant (p = 0.40). The administration of atorvastatin 20 mg showed no effect on the likelihood of developing muscle symptoms (odds ratio 1.11; 99% confidence interval: 0.62 - 1.99). The researchers came to the same conclusion when they analysed only those muscle symptoms for which no other cause (such as vitamin D deficiency) could be found.
A total of 80 volunteers dropped out of the study for various reasons. Of these, 43% dropped out during a statin phase and 49% during a placebo phase. 9% discontinued the study right at the beginning. When filtering for "muscle symptoms" as a reason for discontinuation, there was no difference between the discontinuation times (9% during a statin phase, 7% during a placebo phase).
The results of the StatinWISE study show that myalgias during statin therapy are usually not caused by the statin. Instead, a nocebo effect might be behind it. Previous studies such as GAUSS-3, ODYSSEY ALTERNATIVE and SAMSON are again confirmed by StatinWISE. It is encouraging that about two-thirds of the subjects who completed the study decided to return to statin therapy. It remains questionable whether this is possible for every patient. This is because the study only included patients who were willing to try a statin again.
However, many patients no longer want to take statins after an episode of unpleasant muscle pain. A detailed doctor-patient discussion with a comprehensible therapy algorithm could possibly also convince these patients. This includes educating them about misleading media reports, looking for other causes of muscle pain, trying therapy with at least 3 statins, and determining creatine kinase and liver values before and after each new statin therapy to rule out rare but dangerous statin-associated myopathies.
Reference:
Herrett E et al. Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials. BMJ 2021; 372 (Published 24 February 2021)