A study found that side effects of statins, drugs for hyperlipidemia, have been greatly exaggerated compared with what has been known. Statins, which lower cholesterol levels, are inexpensive drugs that significantly reduce the risk of cardiovascular disease such as heart attacks and strokes, but many people have avoided taking them because of warnings about side effects. Cardiovascular disease claims 20 million lives worldwide every year.
An international team led by Christina Reith of the University of Oxford said in The Lancet on the 4th that only four of the 66 side effects listed in statin package inserts are evidence-based, and even those carry very low risk. The paper reanalyzed studies that had released statin side effects to date without conducting separate clinical trials in patients.
◇ analysis of 23 clinical trials with more than 150,000 participants
Statins are drugs that lower levels of LDL (low-density lipoprotein) cholesterol, which is harmful to the body, and are blockbusters generating sales of 23 trillion won worldwide. In Korea, they are also the reimbursable medicines for which health insurance most often subsidizes drug costs. That means they are prescribed frequently.
The researchers collected data from 23 studies analyzing the effects of the five most commonly prescribed statin-class drugs. Nineteen randomized trials comparing placebo and statins followed 123,940 people for an average of 4.5 years, and four trials compared different statin doses in 30,724 participants.
The team found that, for almost all side effects listed in package inserts, the number of reported adverse events was similar between the statin group and the placebo group. For example, reports of cognitive impairment or memory decline were 0.2% per year in the statin group—identical to the placebo group. A small number of statin users may experience such side effects, but there is no solid evidence that statins are the direct cause.
The analysis found that, among the 66 side effects listed in package inserts, only four—changes in liver function tests, mild liver function abnormalities, urinary changes, and tissue/ankle edema—were associated with statin use. Even so, these appeared in only a very small subset of patients and carried low risk.
In blood tests, the risk of liver function abnormalities increased by 0.1% in the statin group, but the incidence of liver diseases such as hepatitis or liver failure did not increase. This suggests that changes in liver function values generally did not lead to more serious liver problems.
The researchers had also reported in 2022 in The Lancet that most muscle-related side effects, such as myalgia or muscle weakness, do not originate from statins. Only 1% of patients experienced muscle-related side effects in the first year of treatment, with no further increase thereafter.
Reith said, "Statins have been used by hundreds of millions of people over the past 30 years, but concerns about safety have led heart attack and stroke patients to avoid them," adding, "This study reassures us that, for the vast majority of patients, the benefits of statins far outweigh the risks of side effects."
◇ package insert side effect listings should be changed
The study was conducted by the Cholesterol Treatment Trialists' Collaboration (CTT), jointly led by the University of Oxford and the University of Sydney. It was supported by the British Heart Foundation, the U.K. Research and Innovation (UKRI) Medical Research Council, and the National Health and Medical Research Council (NHMRC) of Australia.
Bryan Williams, chief scientific and medical officer at the British Heart Foundation, said, "These findings provide firm reassurance to patients based on authoritative evidence."
Experts argued that package inserts should be revised so patients can take statins with confidence based on these results. Sir Rory Collins, an emeritus professor at the University of Oxford and a corresponding co-author of the paper, said, "We now know that statins do not cause most of the side effects listed in package inserts," adding, "Information on statins should be updated promptly so that patients and clinicians can make better health decisions."
Karol Watson, director of the UCLA Women's Cardiovascular Center, also said, "It is now time for drug regulators to update statin package inserts," adding, "For example, the inserts could clearly indicate which side effects are truly caused by statins and which occur at similar rates among people taking placebo."
Experts in Korea took the same position. Kim Hwiseung, a professor of endocrinology at Chung-Ang University Gwangmyeong Hospital, said, "Excessive fear of statin side effects and the nocebo effect (a reverse placebo in which negative expectations blunt drug efficacy) are emerging as real issues in clinical practice," adding, "Regulatory authorities and public health information must be updated in line with the latest evidence." Kim noted, "This suggests the need for institutional oversight and sanctions for health content that lacks evidence or has not been verified."
◇ the "penicillin of cholesterol" discovered by a Japanese scholar
The findings also prompted a renewed look at the discoverer of statins. Statins were first found in mold by Japanese biochemist Endo Akira and were commercialized in 1973 by the Japanese drugmaker Daiichi Sankyo under the name mevastatin. However, in the early 1980s, animal tests administering high doses to dogs raised concerns about intestinal tumors, leading Sankyo to halt development.
Statins came into full use for treating hyperlipidemia in 1987 when Merck (MSD) in the United States won Food and Drug Administration (FDA) approval to market lovastatin. As a result, lovastatin has been known as the first statin medicine approved in the world.
Endo Akira's contributions were reappraised thanks to the Nobel Prize. Michael Brown and Joseph Goldstein of the University of Texas, who won the 1985 Nobel Prize in physiology or medicine for research related to statins, said in their acceptance remarks, "We dedicate the honor to Endo Akira, who developed the 'penicillin of cholesterol.'"
Alexander Fleming, a British bacteriologist, discovered penicillin, the first antibiotic for humans, in 1928 from blue-green mold. Likewise, Endo was credited with finding the first cholesterol treatment drug in mold.
References
The Lancet (2026), DOI: https://doi.org/10.1016/S0140-6736(25)01578-8
The Lancet (2022), DOI: https://doi.org/10.1016/S0140-6736(22)01545-8