查看文章

In the field of cardiovascular disease (CVD) prevention, much recent attention has naturally focused on the remarkable opportunities afforded by novel lipid-lowering drugs, including monoclonal antibody inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) 1, and inclisiran2. Equally important, are efforts to optimise the use of existing therapies. Statins are commonly available, cheap, safe and effective drugs, which reduce the risk of CV events by approximately 25% per year, for each mmol/L reduction in LDL-C3. Whilst acknowledging that statins might cause adverse effects (including muscle symptoms, new-onset diabetes, and elevation of liver enzymes) in small numbers of treated individuals, it is increasingly clear that statin therapy is strongly associated with the ‘nocebo effect’, whereby adverse effects result from the expectation that an inert substance will relieve or cause a particular symptom. In the case of statin therapy, the ‘expectation’of harm is fuelled by often hostile and unfounded reports on the internet, social media, and in the lay press4. The extent of adverse effects is overestimated owing to the misattribution of unrelated symptoms (such as musculoskeletal injury) 5. The resultant poor rates of compliance with statin therapy inevitably results in unnecessary cardiovascular events4.

Whilst it has long been recognised that reported rates of adverse effects of statin therapy are greater in open label than randomised trials (a fact strongly suggestive of the nocebo effect), the absolute proportion of adverse effects caused by nocebo has been hard to quantify5. Two recent trials have shed light on the issue (Table 1), and important …