Lodz, Poland—Statin intolerance (SI) is dramatically overestimated and over diagnosed worldwide, potentially leading to an increased risk of cardiovascular events, according to a new study.

A meta-analysis published in the European Heart Journal estimates the overall prevalence of SI at 9.1% or even lower using a range of global definitions.

Yet, the international authors point out that as many as half of patients prescribed statins discontinue them, reduce the dose, or follow their drug regimen irregularly because they believe the cholesterol-lowering drugs are causing muscle pain and other side effects.

Based on their review of studies involving more than 4 million patients, the authors point out, “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.”

The overall prevalence of SI, based on different criteria, is estimated at:

• 7.0%, National Lipid Association
• 6.7%, International Lipid Expert Panel
• 5.9%, European Atherosclerosis Society

Researchers advise that female gender, hypothyroidism, high statin dose, advanced age, antiarrhythmics, and obesity can all increase the risk of SI.

“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,” explained lead investigator Maciej Banach, MD, PhD, of the Medical University of Lodz and the University of Zielona Góra, Poland, “Our findings mean that we should evaluate patients’ symptoms very carefully, firstly to see whether symptoms are indeed caused by statins, and secondly, to evaluate whether it might be patients’ perceptions that statins are harmful—so-called nocebo or drucebo effect—which could be responsible for more than 50% of all symptoms, rather than the drug itself.”

Dr. Banach led the research on behalf of the Lipid and Blood Pressure Meta-Analysis Collaboration and the International Lipid Expert Panel (ILEP). The team performed a meta-analysis of 176 studies including 4.1 million patients worldwide in an effort to identify the overall prevalence of SI and the prevalence according to different diagnostic criteria.

The study found that 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 analyzed separately (18% [14–21%], 8.2% [6.0–10%], 9.1% [6.0–11%], respectively).

While statin lipid solubility did not affect the prevalence of SI (4.0% [2.0–5.0%] vs. 5.0% [4.0–6.0%]), several other factors did, including age (odds ratio [OR] 1.33, P = .04), female gender (OR 1.47, P = .007), Asian and Black race (P <.05 for both), obesity (OR 1.30, P = .02), diabetes mellitus (OR 1.26, P = .02), hypothyroidism (OR 1.37, P = .01), and chronic liver and renal failure (P <.05 for both). Also associated with a higher risk of SI were use of antiarrhythmic agents, calcium channel blockers, alcohol use, and increased statin dose, according to the study.

“Based on the present analysis of >4 million patients, the prevalence of SI is low when diagnosed according to international definitions,” the authors conclude. “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.”

They urge clinicians to use their results to encourage adherence to statin therapy in patients.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.