People who know they are being given statins appears more likely to report side effects than those who do not know.

A new study found patients reported side effects in muscles, blood and lymphatic system consistent with the ‘nocebo effect’, where patients report negative effects on their health because they have negative expectations of the treatment they are given.

The study looked at data on 26 side effects from a trial of approximately 10,000 patients, and suggested that cases of muscle pain and weakness are unlikely to be directly caused by statins, but may instead be due to the nocebo effect.

Statins are cholesterol-lowering drugs that have been widely prescribed on the basis that for every 10,000 patients (deemed to be increased risk of heart attacks or strokes), lowering cholesterol with a daily dose of atorvastatin 40mg for 5 years could prevent 1,000 cases of heart attacks, strokes or coronary bypasses.

Its side effects include an increase in the risk of diabetes (50-100 new cases per 10,000 people), haemorrhagic strokes (5-10 per 10,000) and myopathy (5 per 10,000).

The rate of muscle pain and weakness however has been contested, with observational studies in general practice finding that up to a fifth of patients report symptoms, but little to no increase identified in randomised trials. This study helps explain the difference.

“This is not a case of people making up symptoms, or that the symptoms are ‘all in their heads’. Patients can experience very real pain as a result of the nocebo effect and the expectation that drugs will cause harm. What our study shows is that it’s precisely the expectation of harm that is likely causing the increase in muscle pain and weakness, rather than the drugs themselves causing them,” said lead author Professor Peter Sever.

“We know that statins can prevent a significant number of heart attacks and strokes. We know there is a small increase in the risk of diabetes, and at high doses there is a very small increase in myopathy, but overall the benefits greatly outweigh the harms.

“Widespread claims of high rates of statin intolerance still prevent too many people from taking an affordable, safe and potentially life-saving medication.” 

Spanish researchers Dr Juan Pedro-Botet and Dr Juan Rubiés-Prat said it was a useful finding.

“Muscle-related adverse event rates are often argued to be low in randomised controlled trials owing to patient selection,” they wrote in a statement. 

They said the strength of the study lies in the fact that “these were the same patients, no run-in period existed to exclude patients intolerant to therapy, and few patients had previously taken any statins”.

“Additionally, the atorvastatin dose typically used in the non-blinded phase was the same as in the blinded phase.… Given that statins are among the best evidence-based lipid-lowering tools available and suitable for many patients, prevention of intolerance is paramount.

“Thus, physicians should alert their patients to possible statin-associated side-effects without raising negative expectations.

“Furthermore, they should encourage patient understanding of the rationale for statin treatment, which could optimise and facilitate shared decision making on statin therapy.”

The study has been published in The Lancet.