Safety Profile of Statins: An Umbrella Review of Systematic Reviews and Meta-analyses

Background: Statins are a cornerstone of therapy to reduce LDL cholesterol and cardiovascular diseases. However, their use may cause adverse events. This umbrella review aims to comprehensively review the safety profile of statin therapy. Methods: PubMed and Embase were searched to identify systematic reviews, scoping reviews, meta-analyses and network meta-analyses on statin safety. Extracted data included study type, data source, number of included studies, search date range, participant numbers, interventions, safety outcomes, results and funding. Risk of bias was assessed using the AMSTAR 2 instrument. Data underwent descriptive statistical analysis. Results: Seventy-two reviews were included, mostly based on clinical trials (70.8%) and observational studies (59.7%). Only 21 (29.2%) reported results for individual statins, with atorvastatin being the most frequently evaluated individual statin (95.2%). Nearly 86% of the reviews were rated as Critically Low in overall confidence. Statins were associated with an increased risk of new-onset diabetes, particularly rosuvastatin and atorvastatin, whereas pitavastatin may be protective. Liver injury/dysfunction and elevated transaminases were observed, along with a small risk of muscle-related symptoms, specifically at higher statin intensity. Rare serious events, such as necrotising myopathy, were reported. Pregnancy studies indicated an increased risk of spontaneous abortion. Conclusion: Although overall statin safety is favourable, the risks of diabetes, liver dysfunction, enzyme elevations and muscle symptoms require consideration, especially with high-intensity therapy or specific statins. Pitavastatin may be a safer option for patients at metabolic risk. Therapy should be tailored to individual patient factors. Further research is needed to clarify rare or inconsistent outcomes.