The global prevalence of statin intolerance ranges between 6% and 10%, according to a new study published in the European Heart Journal.  

The Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group and the International Lipid Expert Panel (ILEP) conducted a meta-analysis of 176 studies (112 randomized controlled trials (RCTs) and 64 cohort studies) involving with 4,143,517 patients to find out the prevalence of statin intolerance and also factors that predispose to statin intolerance. Researchers also examined the prevalence as per different diagnostic criteria defined by the National Lipid Association (NLA), International Lipid Expert Panel (ILEP) and European Atherosclerosis Society (EAS)].

Results showed the overall prevalence of statin intolerance of 9.1% over a mean follow-up period of 1.5 years ( ± 7.3 months). Comparison of different diagnostic criteria showed still lesser prevalence, but which remained comparable between the three; 5.9% for EAS, 6.7% for ILEP and 7.0% for NLA criteria. Several factors were found to be associated with increased risk of statin intolerance. Older age had 1.33 times greater association with statin intolerance; the odds ratio for female gender was 1.47, for obesity OR was 1.30, for diabetes 1.26 and hypothyroidism 1.37. Patients with chronic liver and kidney failure were also more at risk of statin intolerance as were people of Asian and Black race. No association was observed for statin intolerance with White, Caucasian and Hispanic races.

Alcohol, higher doses of statins and concurrent use of medications like antiarrhythmic agents and calcium channel blockers also increased the risk of statin intolerance. No association was observed for smoking and anticoagulant drugs.

Prevalence of intolerance was similar between lipophilic (atorvastatin, simvastatin, lovastatin, fluvastatin and pitavastatin) and hydrophilic statins (pravastatin and rosuvastatin); 4.0% vs 5.0%, respectively.

The prevalence of statin intolerance was higher in cohort studies (17%) vis-à-vis randomised controlled trials (~5%). The prevalence was higher in studies including both primary and secondary prevention patients (18%) vs primary prevention patients (8.2%) vs secondary prevention patients (9.1%).

Statins are a very commonly prescribed drug. Statin induced myotoxicity (pain, weakness, or cramps) is the most common reason for patients stopping statin treatment. The prevalence of statin intolerance has been shown to be varying widely from 5% to 50%.

According to the authors, this meta-analysis involving more than 4 million patients has for the first time analysed the global prevalence of statin intolerance and also measured it as per different diagnostic criteria. It found the overall prevalence of statin intolerance to be 9 and even less for the different diagnostic criteria. The study has also identified the main risk factors linked to statin intolerance.

This study has shown that statin intolerance is not as common as thought to be. Prof. Maciej Banach, Medical University of Lodz and the University of Zielona Góra, Poland, and lead authors of the study aptly stated: “These results were not a surprise to me but they were for many other experts. They show that in most cases statin intolerance is over-estimated and over-diagnosed, and they mean that around 93% of patients on statin therapy can be treated effectively, with very good tolerability and without any safety issues.”

Patients on statin therapy should therefore be evaluated carefully if they complain of muscular pain to see if the “symptoms are indeed caused by statins”. A nocebo effect should be ruled out. Delineation of risk factors will help to identify at-risk patients. Anticipation of the problem will facilitate interventions to reduce the risk of statin intolerance such as prescribing statins in lower doses, combination therapy.

Given the very low prevalence of statin intolerance as illustrated in this study, and the beneficial effects of statins, patients on statins should be urged to continue taking them and talk to their physicians for any perceived side effects.

Reference

1. Bytyçi I, et al. Prevalence of statin intolerance: a meta-analysis. Eur Heart J. 2022 Feb 16:ehac015. doi: 10.1093/eurheartj/ehac01.