Overall Prevalence of Statin Intolerance: Could It Be Overestimated?

statin therapy treatment, pills
statin therapy treatment, pills
Researchers conducted a meta-analysis to determine real-world prevalence of statin intolerance.

The prevalence of complete statin intolerance might be overestimated worldwide, thus underscoring the need for the careful evaluation of patients with potential symptoms related to statin intolerance. These findings were published in the European Heart Journal.

A meta-analysis was conducted on behalf of the Lipid and Blood Pressure Meta-Analysis Collaboration Group and the International Lipid Expert Panel (ILEP). The investigators sought to estimate the overall prevalence of statin intolerance, to assess the prevalence of statin intolerance based on different diagnostic criteria and in different disease settings, and to identify possible risk factors and conditions that might increase an individual’s risk for statin intolerance.

The primary study endpoint was overall prevalence and prevalence according to a range of diagnostic criteria (from the National Lipid Association [NLA], the ILEP, and European Atherosclerosis Society [EAS]), as well as in different disease settings. The possible risk factors for statin intolerance were considered the secondary endpoint. Databases were searched through May 31, 2021, for studies that have reported on the prevalence of statin intolerance. A random-effects model was utilized to estimate the overall pooled prevalence of statin intolerance.

A total of 176 studies were included in the meta-analysis, 112 of which were randomized controlled trials (RCTs) and 64 of which were cohort studies. Overall, 4,143,517 patients were ultimately included in the meta-analysis.

Results of the study showed that the overall prevalence of statin intolerance was 9.1% (95% CI, 8.0%-10.0%). The prevalence was similar when NLA, ILEP, and EAS criteria were used (overall prevalence, 7.0% [95% CI, 6.0%-8.0%]; overall prevalence, 6.7% [95% CI, 5.0%-8.0%]; and overall prevalence, 5.9% [95% CI, 4.0%-7.0%], respectively).

The prevalence of statin intolerance reported in RCTs was significantly lower than that reported in cohort studies (prevalence, 4.9% [95% CI, 4.0%-6.0%] and prevalence, 17.0% [95% CI, 14.0%-19.0%], respectively).

When studies that compared the prevalence of statin intolerance in patients being treated with statins for both primary and secondary prevention were compared with studies that analyzed statin-treated patients separately (ie, those treated for primary prevention vs those treated for secondary prevention), the prevalence was much higher in those studies that combined primary and secondary prevention than in those that analyzed primary prevention patients separately and those that analyzed secondary prevention patients separately (prevalence, 18.0% [95% CI, 14.0%-21.0%]; prevalence, 8.2% [95% CI, 6.0%-10.0 %]; and prevalence, 9.1% [95% CI, 6.0%-11.0%], respectively).

The prevalence of statin intolerance was not impacted by statin lipid solubility (prevalence, 4.0%; 95% CI, 2.0%-5.0%] vs prevalence, 5.0% [95% CI, 4.0%-6.0%], respectively).

In the meta-regression model, being a woman (odds ratio [OR], 1.47; P =.007), older (OR, 1.33; P =.04), of Asian or Black race (P <.05), and having obesity (OR, 1.30; P =.02), diabetes (OR, 1.26; P =.02), renal failure and chronic liver disease (P <.05 for both), and hypothyroidism (OR, 1.37; P =.01) were all significantly associated with statin intolerance.

The use of calcium channel blockers, antiarrhythmic agents, and alcohol, as well as increased statin dose, were all associated with a higher risk for statin intolerance, as well.

The study authors wrote, “These results support the concept that the prevalence of complete [statin intolerance] is often overestimated and highlights the need for a very careful assessment of patients with [statin intolerance], to decrease the risk of unnecessary statin discontinuation, and suboptimal lipid-lowering therapy. Clinicians should use these results to encourage adherence to statin therapy in their patients.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Bytyçi I, Penson PE, Mikhailidis DP, et al; Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group and the International Lipid Expert Panel (ILEP). Prevalence of statin intolerance: a meta-analysis. Eur Heart J. Published online February 16, 2022. doi:10.1093/eurheartj/ehac015