Safety of lipid-lowering therapies: it is time for a "DOCebo" effect.

Abstract

The expanding range of lipid-lowering therapies offers clinicians unprecedented opportunities to tailor treatment according to efficacy, safety, patient characteristics and preferences. In this context, the systematic review and network meta-analysis by Xie and colleagues provides a timely comparison of the safety profiles of lipid-lowering drugs, drawing on 153 randomized trials involving more than 303,000 participants. The analysis suggests that PCSK9 monoclonal antibodies have the most favourable profile for creatine kinase elevation, new-onset diabetes and liver dysfunction, whereas bempedoic acid ranks best for myalgia risk. No clear increase in cognitive disorders was identified across treatment classes. These findings are clinically relevant because concerns regarding muscle symptoms, diabetes and cognitive impairment frequently contribute to treatment refusal, poor adherence and discontinuation, particularly with statins. The results support a personalized approach aimed at achieving the required LDL-C reduction while maximizing long-term persistence. Effective communication is equally important as misinformation and the nocebo effect may undermine adherence. Clinicians should therefore promote an evidence-based "DOCebo" effect through trust, shared decision-making and clear counselling. Ultimately, safety should guide treatment personalization without displacing absolute cardiovascular benefit as the primary determinant of therapy.