Statin Intolerance 'Overestimated and Overdiagnosed'

Megan Brooks

February 16, 2022

Statin intolerance is far less common than previously reported, according to a new meta-analysis, with data on more than 4 million adults from around the world, looking at reported statin adverse effects.

The study puts the prevalence of statin intolerance at 6% to 10%, meaning that statin intolerance is "overestimated and overdiagnosed" in most cases, Maciej Banach, MD, PhD, from the Medical University of Lodz and the University of Zielona Góra, Poland, said in a news release.

It also means that "around 93% of patients on statin therapy can be treated effectively, with very good tolerability and without any safety issues," Banach added.

The study, conducted on behalf of the Lipid and Blood Pressure Meta-Analysis Collaboration and the International Lipid Expert Panel, was published online February 16 in the European Heart Journal.

Reassuring Data

In a statement from the British nonprofit Science Media Center, Sir Nilesh J. Samani, MBChB, MD, medical director of the British Heart Foundation, said: "Decades of evidence have proven that statins save lives. This latest analysis, showing that the risk of side effects from statins are less than previously thought, should provide reassurance to those who are recommended this medicine to reduce their risk of a heart attack or stroke."

The reported prevalence of statin intolerance varies widely, from 2% to 3% to as high as 50%, chiefly because "there is still a lack of a clear and easy way to apply the definition of statin intolerance," Banach told theheart.org | Medscape Cardiology.

"The ones we use in lipid clinics — by National Lipid Association (NLA), European Atherosclerosis Society (EAS) and International Lipid Expert Panel (ILEP) — are not used or are rarely used in everyday clinical practice by GPs and other specialists," Banach explained.

He also blames "physician inertia; when they listen to a patient complain of muscle pain, or see elevated alanine aminotransferase (ALT), in most of the cases, they will immediately discontinue statins, without any further investigations. One should remember that there are many secondary causes of statin intolerance," Banach said.

To get a better handle on the true prevalence of statin intolerance, the study team did a meta-analysis of 4,143,517 patients worldwide from 176 studies: 112 randomized controlled trials and 64 cohort studies.

The overall prevalence of statin intolerance was 9.1% (95% CI, 8.0% - 10.0%).

The prevalence of statin intolerance was even lower when assessed with diagnostic criteria from the NLA (7.0%; 95% CI, 6.0% - 8.0%), the ILEP (6.7%; 95% CI, 5.0% - 8.0%), and the EAS (5.9%; 95% CI, 4.0% - 7.0%).

The main factors associated with an increased risk for statin intolerance are female gender, hypothyroidism, high statin dose, advanced age, concomitant use of anti-arrhythmic drugs, and obesity. Other factors include race (being Asian or African American), type 2 diabetes, alcohol use, and chronic liver and renal diseases.

"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," Banach said.

He encourages use of the Statin-Associated Muscle Symptom Clinical Index (SAMS-CI) to assess the likelihood that a patient's muscle symptoms are caused or worsened by statin use.

Substantial Analysis, Valid Results

"This is a substantial analysis [and], based on what we know about statin side effects to date, the results are likely to be broadly valid, and indicate that we should not overestimate statin side effects or be too quick to stop statins without due consideration," Riyaz Patel, MBBS, professor of cardiology, University College London, told the Science Media Center.

"Some patients do experience real side effects and we do our best to help them with alternative therapies, as with any other medicine. However, for the vast majority of people experiencing statin side effects, we can usually work with the patient to understand the symptoms, use proven strategies to manage these, and ensure they do not miss out on the well-established benefits of statins," Patel said.

"This is especially important for people who have already had a heart attack or stroke, where statin therapy is really important in preventing further events," Patel added.

Also weighing in on the results, Peter Sever, MB BChir, professor of clinical pharmacology and therapeutics, Imperial College London, said: "The importance for clinicians and patients is to realize that commonly reported symptoms, such as muscle aches and pains and lethargy, are not due to the chemistry of the drug."

"These 'nocebo' symptoms may be psychological in origin but they are no less real than pharmacological symptoms in how they affect quality of life," Sever told the Science Media Center.

"However, it's important to note that as they are not directly caused by the drug, they should not override the decision to prescribe and take statins on account of their proven benefit in reducing death and disability from heart attacks, strokes, and other cardiovascular conditions," he added.

This meta-analysis was conducted independently; no company or institution supported it financially. Banach is on the speakers bureau for Amgen, Herbapol, Kogen, KRKA, Polpharma, Mylan/Viatris, Novartis, Novo Nordisk, Sanofi-Aventis, Teva, and Zentiva; is a consultant to Abbott Vascular, Amgen, Daichii Sankyo, Esperion, FreiaPharmaceuticals, Novartis, Polfarmex, and Sanofi-Aventis; has received grants from Amgen, Mylan/Viatris, Sanofi, and Valeant; and serves as CMO for Nomi Biotech Corporation. Samani has no relevant disclosures. Patel has received past honoraria and consulting fees from drug companies manufacturing new cholesterol-lowering drugs, and currently work with NICE as a topic advisor for CVD prevention. Sever has received research grants and consultancy from Pfizer and Amgen.

Eur Heart J. Published online February 16, 2022. Full text

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