Prevalence of statin intolerance: a meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized trials and cohort studies
PubMed 35169843 · doi:10.1093/eurheartj/ehac015
What was done
A systematic review and random-effects meta-analysis was conducted across databases up to May 31, 2021, to estimate the prevalence of statin intolerance (SI) and identify associated risk factors. A total of 176 studies (112 randomized controlled trials and 64 cohort studies) comprising 4,143,517 patients were included. Primary endpoints were overall prevalence, prevalence according to established criteria (National Lipid Association [NLA], International Lipid Expert Panel [ILEP], European Atherosclerosis Society [EAS]), and prevalence across clinical settings.
What was found
Overall pooled SI prevalence was 9.1% (95% CI 8.0-10%). By diagnostic criteria, prevalence was 7.0% (95% CI 6.0-8.0%) for NLA, 6.7% (95% CI 5.0-8.0%) for ILEP, and 5.9% (95% CI 4.0-7.0%) for EAS. Prevalence was significantly lower in RCTs than in cohort studies (4.9% [95% CI 4.0-6.0%] vs 17% [95% CI 14-19%]). Combined primary and secondary prevention settings reported higher prevalence (18% [95% CI 14-21%]) than separate primary (8.2% [95% CI 6.0-10%]) or secondary prevention (9.1% [95% CI 6.0-11%]). Lipid solubility did not significantly alter prevalence (4.0% vs 5.0%). Meta-regression identified age (OR 1.33, P = 0.04), female gender (OR 1.47, P = 0.007), Asian and Black race (P < 0.05 for both), obesity (OR 1.30, P = 0.02), diabetes mellitus (OR 1.26, P = 0.02), hypothyroidism (OR 1.37, P = 0.01), chronic liver and renal failure (P < 0.05 for both), antiarrhythmic agents, calcium channel blockers, alcohol use, and increased statin dose as significant risk factors.
Why it matters
True statin intolerance is relatively low (under 10% across standardized criteria and under 5% in randomized trials), suggesting that symptoms attributed to statins in routine clinical practice are frequently overestimated.
Limits
The meta-analysis is limited by marked heterogeneity between study designs, with cohort studies reporting over three times the intolerance rate of randomized trials. The abstract does not report whether symptom verification or re-challenge protocols were uniformly applied across included studies.
Cited by
- partial Approximately 20% of statin users experience muscle damage, muscle symptoms, or an increased risk of diabetes.