A Closer Look at Statin Safety. An article by 3rd year medical student Michelle Mazur
A Closer Look at Statin Safety
Statins are among the most widely studied medications in medicine and have been shown to significantly reduce the risk of heart attacks, strokes, and cardiovascular death by lowering LDL (“bad”) cholesterol (1). Despite this, myths about their safety continue to circulate.
Why Statins Matter
We know that statins lower cholesterol, but why does that matter? Cholesterol can act like a sticky buildup inside blood vessels, and as that buildup increases, blood has a harder time flowing properly. Oxygen, which is carried through the blood, also has a harder time reaching organs. For example, when this occurs in the blood vessels of the heart, individuals may begin to experience chest pain or shortness of breath with lower levels of activity.
Image from: https://www.news-medical.net/health/Statin-History.aspx
Another concern is that a cholesterol plaque can rupture and suddenly block blood flow. When this occurs in the heart or brain, it can cause a heart attack or stroke. Statins are effective at lowering cholesterol, and randomized controlled trials have consistently demonstrated that lowering LDL cholesterol with statins reduces cardiovascular disease (2).
Statins in Prevention
Statins are used for both primary prevention and secondary prevention of cardiovascular disease.
Primary prevention means preventing a first heart attack or stroke in patients who are at high risk.
Secondary prevention refers to preventing another cardiovascular event in patients who have already experienced a heart attack, stroke, or established cardiovascular disease.
Research has consistently shown that statins reduce the risk of major cardiovascular events in both groups, with particularly strong benefits in secondary prevention (3)
Muscle Pain Does Not Always Mean Muscle Damage
One of the most common concerns about statins is muscle pain. However, research shows that muscle symptoms without elevated creatine kinase (CK) levels are often caused by another condition or by the “nocebo effect,” where expectations of side effects can contribute to symptoms (4).
In a Cochrane Foundation analysis of more than 35,000 patients receiving statins across nine clinical trials, the rate of muscle pain was similar between patients taking statins and those receiving a placebo, a “fake” medication used for comparison in clinical research (5).
Despite this, muscle pain can feel very real and is a common reason why patients stop taking their statin medication. If this sounds familiar, it is important to speak with a healthcare provider before discontinuing treatment. In many cases, switching to a different statin or adjusting the dose can significantly improve symptoms. Muscle pain itself is typically not life-threatening, but the consequences of a heart attack or stroke can be devastating.
Severe Muscle Injury Is Extremely Rare
A more serious condition called rhabdomyolysis, or severe muscle breakdown, can occur. However, it is exceedingly rare. A study that analyzed all the reports of rhabdomyolysis through VigiBase, the largest pharmacovigilance database in the word, noted that in over 33 million reports of rhabdomyolysis documented from 1968 until 2022, only 10,657 were associated with statins (6). This corresponds to an approximate risk of just 0.03%! Therefore, while this risk exists, the danger of untreated high cholesterol is far greater.
Rare Side Effects to Watch For
Although statins are generally very safe, patients should still be aware of uncommon warning signs, including:
unusual fatigue
loss of appetite
upper abdominal discomfort
dark-colored urine
yellowing of the skin or eyes
These symptoms should be discussed with a healthcare provider.
The Bottom Line
No medication is completely without risk, but statins are often portrayed as far more dangerous than the evidence supports. For most patients, the benefits of reducing cardiovascular disease greatly outweigh the small risk of rare, serious side effects. Evidence-based medicine, not fear or misinformation, should guide treatment decisions.
Image from: https://www.nytimes.com/2018/04/16/well/weighing-the-pros-and-cons-of-statins.html
Some websites to check out:
https://my.clevelandclinic.org/health/treatments/22282-statins
https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/statins/art-20045772
https://www.ottawaheart.ca/the-beat/news/the-benefits-and-risks-statins
References available online.
Gupta S. (2015). LDL cholesterol, statins and PCSK 9 inhibitors. Indian heart journal, 67(5), 419–424. https://doi.org/10.1016/j.ihj.2015.05.020
Montastruc J. L. (2023). Rhabdomyolysis and statins: A pharmacovigilance comparative study between statins. British journal of clinical pharmacology, 89(8), 2636–2638. https://doi.org/10.1111/bcp.15757
Kadoglou, N. P. E., & Stasinopoulou, M. (2023). How to Use Statins in Secondary Prevention of Atherosclerotic Diseases: from the Beneficial Early Initiation to the Potentially Unfavorable Discontinuation. Cardiovascular drugs and therapy, 37(2), 353–362. https://doi.org/10.1007/s10557-021-07233-8
Moon, J., Cohen Sedgh, R., & Jackevicius, C. A. (2021). Examining the Nocebo Effect of Statins Through Statin Adverse Events Reported in the Food and Drug Administration Adverse Event Reporting System. Circulation. Cardiovascular quality and outcomes, 14(1), e007480. https://doi.org/10.1161/CIRCOUTCOMES.120.007480
Montastruc J. L. (2023). Rhabdomyolysis and statins: A pharmacovigilance comparative study between statins. British journal of clinical pharmacology, 89(8), 2636–2638. https://doi.org/10.1111/bcp.15757
Connie B. Newman. Safety of Statins and Nonstatins for Treatment of Dyslipidemia. Endocrinology and Metabolism Clinics of North America, 51 (3). 655-679. https://doi.org/10.1016/j.ecl.2022.01.004.
