What You Need to Know About Statins
At-a-Glance:
- Statins are the workhorse of cardiovascular medicine.
- Healthcare providers write more than 800 million statin prescriptions each year, costing consumers and the U.S. healthcare system more than $10 billion.
- Statins are effective, but they are not equally helpful for all patients.
By Dr. John Neustadt
Statins are the workhorse of cardiovascular medicine. The FDA approved statins for lowering cholesterol and triglycerides and for treating atherosclerosis. Their benefits and risks have been extensively studied, and the evidence supports their use for many patients.
However, understanding these benefits and risks is essential when deciding whether this medication is a good fit for you. Statins clearly prevent heart attacks, strokes, and all-cause mortality; however, they are not equally helpful for all patients, and the decision must be individualized based on someone’s medical history and risk level.
Statins history
Statins were discovered in 1976 when Japanese microbiologist Akira Endo isolated the first statin, mevastatin, from the fungus Penicillium citrinum. This discovery was pivotal as it identified a potent inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Blocking HMG-CoA decreases the body’s ability to create cholesterol.1-3
In 1987, the FDA approved the first statin, lovastatin (Mevacor), derived from another fungus, Aspergillus terreus.4 Since then, many medications in this class have been approved, including atorvastatin (Lipitor), fluvastatin (Lescol XL), pravastatin (Prevachol), rosuvastatin (Crestor), and simvastatin (Zocor, Vytorin).
The American Heart Association (AHA) clinical guidelines for managing cardiovascular disease risk include statins as the “cornerstone” of this approach.
Healthcare providers write more than 800 million statin prescriptions each year, costing consumers and the U.S. healthcare system more than $10 billion. Despite that, the medical literature is full of claims that statins are being “underutilized,” with guidelines that seek to increase the number of people taking these medications.5
Large effect on cholesterol
The goal of statin therapy is to reduce someone’s risk for heart attacks and strokes by lowering elevated low-density lipoprotein (LDL) cholesterol, a risk factor for heart disease.
The higher the medication dose, the greater the effect. Data from large populations and randomized controlled trials show how much these medications lower LDL at different doses.6
High dose
For example, taking 20-40 mg of rosuvastatin or 40-80 mg of atorvastatin daily is a high dose. This typically reduces LDL by 50% or more.
Moderate dose
Taking 5-10 mg of rosuvastatin, 10-20 mg of atorvastatin, or 20-40 mg of simvastatin is moderate dose. This typically reduced LDL to 30-49%.
Low dose
Taking 10 mg of simvastatin, 10-20 mg of pravastatin, or 20 mg of lovastatin typically lowers LDL by less than 30%.
Overall benefits
While this category of drugs is effective at reducing cholesterol, it’s less effective at reducing all-cause mortality, heart attacks, and strokes. For example, while statins reduce LDL cholesterol by 30% to more than 50%, they do not improve one’s risk for a cardiovascular event like a heart attack or stroke by the same amount.
The best measurement to understand if a patient will benefit from a medication is called absolute risk reduction (ARR). According to the National Institutes of Health National Center for Biotechnology Information, ARR “is the most useful way of presenting research results to help your decision-making.”7
The potential benefits of taking a statin depend on whether it is used for primary or secondary prevention and your cardiovascular disease risk level. Primary prevention means someone doesn’t yet have heart disease but has risk factors, and doctors are trying to prevent it from developing. Secondary prevention means someone has already had a heart attack or stroke, and doctors are trying to prevent it from happening again.
Benefits in controlled clinical trials
A systematic review and meta-analysis of twenty-one clinical trials that followed patients for up to six years concluded that the benefits are “modest.” The researchers found for primary prevention, statins reduce the absolute risk of all-cause mortality by 0.6%, heart attacks by 0.7%, and strokes by 0.3%. This means that 167 people would have to take a statin for six years to prevent one death, 143 people to prevent one heart attack, and 333 people to prevent one stroke.8
The higher the risk, the greater the benefits
The benefits of statin therapy also vary depending on a person’s cardiovascular disease (CVD) risk. Multiple risk calculators exist; however, they all seem to consider standard variables such as age, sex, race, blood pressure, total, LDL, and HDL cholesterol levels, whether the person has diabetes, smokes, is on medication for high blood pressure, or is taking a statin.
If a person has already had a cardiovascular event (e.g., heart attack or stroke), they are automatically in the highest risk category. To understand which category you fall into, you can ask your doctor to calculate it or use one of the free online calculators like the one from the American College of Cardiology.
The American College of Cardiology and the American Heart Association guidelines conclude that patients at the highest risk experience the greatest benefits.9
A meta-analysis published in The Lancet supports this. It found that statins reduce the absolute risk of heart attacks and strokes by 1.1% to 3.1%, depending on one’s risk level. This means that if 100 low-risk patients took statins, the medication would prevent one heart attack or stroke. For the highest-risk patients, for every 100 people taking a statin, about three heart attacks or strokes would be prevented.10
Statin Side Effects
As I discuss in my book on osteoporosis, Fracture-Proof Your Bones, any conversation about medications is incomplete if it does not include the potential risks. The risks of being on statins for five years or longer include several well-documented problems.
Similar to other medications that cause bone loss and osteoporosis, the higher the statin dose, the greater the risks. According to a population-based cohort study, the absolute risks for specific side effects over five years are:11
Muscle symptoms: One patient with muscle symptoms would be expected for every 259 women or 91 men taking a statin.
Liver dysfunction: For every 136 women taking a statin for more than five years, we expect one will experience this. The risk in men is one new case for every 155 patients.
Renal insufficiency (acute kidney failure): For every 434 women and 447 men taking a statin, we expect one to experience kidney problems.
Cataracts: For every 33 women and 66 men taking a statin, we expect one to develop cataracts.
Holistic approaches
While medication might be a good choice depending on your risk profile, applying evidence-based holistic approaches is also essential.
Diet
According to a systematic review and meta-analysis, the Mediterranean diet, emphasizing increasing consumption of fish (high in omega-3 fatty acids), fruit, vegetables, and monounsaturated fats (e.g., olive oil), reduced the absolute risk of death by 1.7% over five years for people at intermediate cardiovascular disease risk. This is better than the absolute risk reduction of 0.9% for low-fat dietary programs and statins. The Mediterranean diet also reduces the risk of stroke and non-fatal heart attacks.12
Combining statins with a Mediterranean dietary pattern has even greater benefits than taking statins by themselves, even in high-risk patients who already have cardiovascular disease.13 This is why dietary modification is always recommended, even when people are taking a statin.
Exercise
Even in advanced cases, exercise helps. According to a meta-analysis of 85 randomized controlled clinical trials, exercise-based cardiac rehabilitation (CR) for people recovering from a heart attack, with angina, or following coronary artery bypass graft (CABG) surgery reduced the risk of dying from cardiovascular disease by 2.7%. The study concluded that one year of exercise can prevent one death for every 37 people. One heart attack can also be prevented for every 100 patients exercising for one year.14
While exercise is an essential part of a heart-healthy program, it is crucial to do it safely. If you have risk factors for heart disease or have been diagnosed with it, speak to your healthcare provider before starting an exercise program.
Mental health
More research is now recognizing stress and depression as modifiable risk factors for heart disease. While the American Heart Association (AHA) guidelines don’t yet recognize anxiety and depression as modifiable risks for heart disease, European guidelines do.15 In addition to exercise, clinical trials indicate that yoga and meditation improve mental health and decrease cardiovascular events, even in high-risk individuals.16,17
Sleep
Getting enough sleep is essential for cardiovascular health. The research is clear, with potential underlying mechanisms including hypothalamic-pituitary axis dysregulation, increased sympathetic nervous system activity, and increased inflammation.18 For suggestions on improving sleep, see the Checklist for Better Sleep.
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References
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6 Grundy SM, Stone NJ, Bailey AL, et al. 2018 2019;139(25):e1082-e1143.
7 Irwig L, Irwig J, Trevena L, Sweet M. Hammersmith Press; 2008.
8 Byrne P, Demasi M, Jones M, et al. 2022;182(5):474-481.
9 Gulati M, Levy PD, Mukherjee D, et al. 2021;144(22):e368-e454.
10 Mihaylova B, Emberson J, Blackwell L, et al. 2012;380(9841):581-90.
11 Hippisley-Cox J, Coupland C. 2010;340:c2197.
12 Karam G, Agarwal A, Sadeghirad B, et al. 2023;380:e072003.
13 Bonaccio M, Di Castelnuovo A, Costanzo S, et al. 2019;276:248-254.
14 Dibben GO, Faulkner J, Oldridge N, et al. 2023;44(6):452-469.
15 Piepoli MF, Hoes AW, Agewall S, et al. 2016;37(29):2315-2381.
16 Chu P, Pandya A, Salomon JA, et al. 2016;5(3):e002737.
17 Schneider RH, Grim CE, Rainforth MV, et al. 2012;5(6):750-8.
18 Javaheri S, Redline S. 2017;152(2):435-444.
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