Aims

Statin intolerance (SI) represents a significant public health problem for which precise estimates of prevalence are needed. Statin intolerance remains an important clinical challenge, and it is associated with an increased risk of cardiovascular events. This meta-analysis estimates the overall prevalence of SI, the prevalence according to different diagnostic criteria and in different disease settings, and identifies possible risk factors/conditions that might increase the risk of SI.

Methods and results

We searched several databases up to 31 May 2021, for studies that reported the prevalence of SI. The primary endpoint was overall prevalence and prevalence according to a range of diagnostic criteria [National Lipid Association (NLA), International Lipid Expert Panel (ILEP), and European Atherosclerosis Society (EAS)] and in different disease settings. The secondary endpoint was to identify possible risk factors for SI. A random-effects model was applied to estimate the overall pooled prevalence. A total of 176 studies [112 randomized controlled trials (RCTs); 64 cohort studies] with 4 143 517 patients were ultimately included in the analysis. The overall prevalence of SI was 9.1% (95% confidence interval 8.0-10%). The prevalence was similar when defined using NLA, ILEP, and EAS criteria [7.0% (6.0-8.0%), 6.7% (5.0-8.0%), 5.9% (4.0-7.0%), respectively]. The prevalence of SI in RCTs was significantly lower compared with cohort studies [4.9% (4.0-6.0%) vs. 17% (14-19%)]. The prevalence of SI in studies including both primary and secondary prevention patients was much higher than when primary or secondary prevention patients were analysed separately [18% (14-21%), 8.2% (6.0-10%), 9.1% (6.0-11%), respectively]. Statin lipid solubility did not affect the prevalence of SI [4.0% (2.0-5.0%) vs. 5.0% (4.0-6.0%)]. Age [odds ratio (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) were significantly associated with SI in the meta-regression model. Antiarrhythmic agents, calcium channel blockers, alcohol use, and increased statin dose were also associated with a higher risk of SI.

Conclusion

Based on the present analysis of >4 million patients, the prevalence of SI is low when diagnosed according to international definitions. These results support the concept that the prevalence of complete SI might often be overestimated and highlight the need for the careful assessment of patients with potential symptoms related to SI.

Quercetin, the most abundant dietary flavonol, has antioxidant effects in cardiovascular disease, but the evidence regarding its effects on blood pressure (BP) has not been conclusive. We assessed the impact of quercetin on BP through a systematic review and meta-analysis of available randomized controlled trials. We searched PUBMED, Cochrane Library, Scopus, and EMBASE up to January 31, 2015 to identify placebo-controlled randomized controlled trials investigating the effect of quercetin on BP. Meta-analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Effect size was expressed as weighted mean difference (WMD) and 95% CI. Overall, the impact of quercetin on BP was reported in 7 trials comprising 9 treatment arms (587 patients). The results of the meta-analysis showed significant reductions both in systolic BP (WMD: -3.04 mm Hg, 95% CI: -5.75, -0.33, P=0.028) and diastolic BP (WMD: -2.63 mm Hg, 95% CI: -3.26, -2.01, P<0.001) following supplementation with quercetin. When the studies were categorized according to the quercetin dose, there was a significant systolic BP and diastolic BP-reducing effect in randomized controlled trials with doses ≥500 mg/day (WMD: -4.45 mm Hg, 95% CI: -7.70, -1.21, P=0.007 and -2.98 mm Hg, 95% CI: -3.64, -2.31, P<0.001, respectively), and lack of a significant effect for doses <500 mg/day (WMD: -1.59 mm Hg, 95% CI: -4.44, 1.25, P=0.273 and -0.24 mm Hg, 95% CI: -2.00, 1.52, P=0.788, respectively), but indirect comparison tests failed to significant differences between doses. The results of the meta-analysis showed a statistically significant effect of quercetin supplementation in the reduction of BP, possibly limited to, or greater with dosages of >500 mg/day. Further studies are necessary to investigate the clinical relevance of these results and the possibility of quercetin application as an add-on to antihypertensive therapy.