Worldwide prevalence of statin intolerance
Prevalence of statin intolerance: a meta-analysis
Introduction and methods
Statin-associated muscle symptoms (SAMS) are the most common cause of discontinuation of statin therapy [1,2]. The estimated prevalence of statin intolerance (SI) ranges from 5-7% in RCTs to 30% in cohort studies [3,4]. However, this prevalence is debated as symptoms may be attributable to a nocebo/drucebo effect .
In this meta-analysis, the overall prevalence of SI, the prevalence according to various diagnostic criteria, and in different disease setting are estimated, and possible risk factors for SI are identified.
PubMed-Medline, EMBASE, Scope, Google Scholar, the Cochrane Central Registry of Controlled Trials and ClinicalTrial.gov were searched. Articles were eligible if they reported the prevalence of SI either in primary or secondary prevention and met the following criteria: trials or cohorts reporting SI; ≥100 participants; and available criteria for SI diagnosis. 176 Studies with 4,143,517 patients and mean follow-up of 19 ± 7.3 months were included; 112 were RCTs and 64 were cohort studies.
Primary endpoint was the overall prevalence and the prevalence based on each of the international diagnostic criteria: NLA , EAS  and ILEP . Secondary endpoint was the prevalence of SI in groups of patients with different diseases and the analysis of the association between possible risk factors/conditions and risk of SI.
Prevalence of statin intolerance
- Pooled prevalence of SI was 9.1% (95%CI: 8.0-10.0%).
- Prevalence based on NLA criteria was similar compared with that based on ILEP or EAS criteria (7.0%, 6.7%, and 5.9%. respectively).
- Prevalence of SI in RCTs was lower compared with that in cohort studies (4.9% [4.0-6.0%] vs. 17% [14-19%], P<0.001).
- SI was more common in pooled analysis of studies including both primary and secondary prevention patients (18% [14-21%]), than in either pooled analyses of studies including only primary or secondary prevention patients (8.2% [6.0-10%], 9.1% [6.0-11%], respectively).
- In primary prevention patients with FH, hypercholesterolemia, dyslipidemia, T2DM, prevalence of SI was 9%, 12%, 13% and 6%, respectively. In secondary prevention patients with stable coronary artery disease, acute coronary syndrome, myocardial infarction, and stroke/transient ischemic attack this was 8%, 13%, 13%, 5%, respectively.
- Prevalence of SI was similar in lipophilic and hydrophilic statins.
Risk factors for statin intolerance
- Age ≥65 years and female sex were associated with higher risk for SI (OR 1.31, 95%CI:1.22-1.45, P=0.04; OR 1.47, 95%CI:1.38-1.53, P=0.007, respectively).
- Prevalence of SI was associated with percentage of participants of Asian and African-American race (P<0.05 for both).
- Positive associations between clinical factors and prevalence of SI were found for obesity (OR 1.30, P=0.02), diabetes (OR 1.26, P=0.02), hypothyroidism (OR 1.37, P=0.01), chronic liver disease (OR 1.24, P=0.03) and chronic renal failure (OR 1.25, P=0.03). A negative association with SI was found for percentage of patients with depression (OR 0.88, P=0.04).
- Percentage of alcohol users was associated with prevalence of SI (OR 1.22, P=0.03). Exercise (OR 1.23, P=0.03), calcium channel blockers (OR 1.31, P=0.03) and antiarrhythmic agents (OR 1.35, P=0.03) were associated with higher risk of SI. Also, increased statin dose was associated with a higher prevalence of SI (OR 1.37, P=0.01).
This meta-analysis of 176 studies with 4,143,517 patients demonstrated that the worldwide prevalence of statin intolerance is 9.1%, and is independent of the criteria that are used. Risk factors of SI include older age, female gender, Asian and African-American races, obesity, T2DM, alcohol use, exercise, hypothyroidism, chronic liver and renal diseases, high statin doses, antiarrhymic agents and calcium channel blockers.
The authors conclude: “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”.