European Heart Journal: September, 2022

Cardiovascular (CV) disease (CVD) is the leading cause of morbidity and mortality worldwide, despite continuous improvement of medical treatment, diagnosis, and risk factor control. It has been clearly demonstrated that statin therapy confers significant mortality and morbidity benefits in both the primary and secondary prevention of CVD. 

Statin intolerance and the discontinuation of statin therapy is an ongoing clinical problem worldwide. Statin intolerance is associated with suboptimal lipid-lowering therapy and a high risk of first and recurrent CVD events. 

Statin Intolerance (SI) refers to an inability to tolerate ≥2 statins at any dose or an inability to tolerate increasing doses. The symptoms must not be attributable to drug–drug interactions or conditions known to increase SI. 

Symptomatic criteria include intolerable muscle symptoms [pain, weakness, or cramps with or without creatine kinase (CK) changes] or severe myopathy, and they must appear in the first 12 weeks after initiating treatment or following an increase in dose.

Numerous studies, systematic reviews, and meta-analyses have demonstrated an association between statin non-adherence and discontinuation and the risk of CVD and mortality.

The present meta-analysis aimed to estimate the overall prevalence of SI, its prevalence according to various diagnostic criteria, in different disease settings, and to identify possible risk factors for SI.

TAKE-HOME MESSAGE

The most common cause of discontinuation of statin therapy is statin-associated muscle symptoms (SAMS). Other possible statin-related adverse effects include neurocognitive disorders, hepatotoxicity, haemorrhagic stroke, and renal toxicity.

This meta-analysis estimated overall statin intolerance (SI) prevalence and identified factors that might increase the risk of SI. Combining data from 176 studies with >4 million patients, the prevalence of SI was 9.1%.

Additionally, SI prevalence was lower in randomized controlled trials than in cohort studies. Age, female gender, high statin dose, Asian and Black race, obesity, diabetes mellitus, alcohol use, hypothyroidism, and chronic liver and renal failure were identified as risk factors for SI, as were increased statin doses and the concomitant administration of antiarrhythmic agents.

Statins are the main treatment to reduce LDL-C levels and to reduce ASCVD risk. Identifying true SI is important in order to avoid unnecessary statin discontinuation, especially in high ASCVD–risk patients.

Although the prevalence of SI is relatively low, identification of risk factors and their management in high ASCVD–risk patients is important to encourage statin adherence and therefore to reduce cardiovascular risk.

Conclusion

Based on the data from >4 million patients, authors demonstrated that the overall prevalence of Statin intolerance (SI) is relatively low.

These results support the concept that the prevalence of complete SI is often overestimated and highlights the need for a very careful assessment of patients with SI, 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.

It is also necessary to advise patients on what to do if they have muscle complaints, including temporary discontinuation, statin re-challenge, down-titration of dose or switching to  another statin, or evaluating other therapeutic alternatives with proven effectiveness in reducing CV risk, like ezetimibe or PCSK9 inhibitors.

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