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Physician associates (PAs) manage heart disease, high blood pressure, and everything in between. One of the most common medications they prescribe are statins. Statins are a medication that lowers cholesterol and reduces the risk of heart attack and stroke. Statins are not without side effects and they are quite misunderstood, even maligned. What is the truth about statins in 2023?
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Domo arigato, Dr. Endo.
Dr. Akira Endo, along with many others, recognized the growing problem of high blood cholesterol and heart disease. But available medications in the 1950s and 60s were not very effective and not well tolerated–the Framingham Heart Study (among others) had only recently cemented the link between the two.
This was also the era of antibiotics. Alexander Fleming discovered penicillin a few decades prior and pharmaceutical companies were actively searching for new antibiotics. Dr. Endo hypothesized that if enzymes in mold could be harnessed to interfere with processes in bacteria, they might also be able to interfere with the process of cholesterol synthesis in humans.
Lovastatin is born.
Building upon the research of Japanese chemist Akira Endo, the first commercial statin, lovastatin, was derived from the fungus Aspergillus terreus and released in 1987 as Mevacor. A study of over 6,000 men and women in Texas who had elevated cholesterol but no history of heart disease found that coronary events were reduced by almost 40%. Coronary events were defined as a heart attack, severe chest pain (angina), or sudden cardiac death.
The benefits of lovastatin were consistent across smokers and non-smokers, older patients and younger patients, and those with high blood pressure and normal blood pressure. Merck, the manufacturer of the first commercialized statin, recommended that lovastatin, or Mevacor, only be used as an adjunct to a healthful diet and when the response to diet alone was inadequate to reduce risk.
The 77-year-old Dr. Endo noted in 2010 that by that time almost 100,000 people had been involved in statin-related studies. Results were consistent across all major studies: statins reduced LDL cholesterol (often called bad cholesterol) by up to 35%. More importantly, was the fact that the medication reduced heart attacks by up to 30%. Today, the total number of individuals involved in statin research is closer to 200,000.
Statin Side Effects
This new miracle treatment was not without side effects, however. The following statements could be found in the Mevacor package insert: Lovastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness, or weakness. The 1991 EXCEL study found one case of myopathy among almost 5,000 patients taking up to 40 mg of lovastatin over 3 years. In another trial of over 1,600 patients, there were 4 cases among those taking 80 mg of lovastatin.
Muscle soreness is, in fact, the most common side effect seen in clinical practice but only 1 out of every 10 patients actually stop taking a statin because of the side effects.
How to Reduce Statin Side Effects
There are several “tricks” to improve statin tolerability, though evidence indicates that they may not work for everyone.
- Vitamin D
- Many people are low in Vitamin D. Some clinicians recommend taking 2,000 IU daily whether they have trouble tolerating statin drugs or not.
- CoQ10 (Coenzyme Q10)
- CoQ10 is an antioxidant that gets depleted by statins. Supplementing CoQ10 seems to help improve medication adherence for some.
- Statin selection
- Hydrophilic statins such as rosuvastatin, fluvastatin, and pravastatin are often the best tolerated.
- Alternate dosing regimens
- Multiple studies, including this one from the Canadian Journal of Cardiology, shows that every-other-day dosing is still effective in reducing bad LDL cholesterol. Improvements in the good HDL cholesterol and triglycerides were actually unchanged compared to daily dosing.
- Take a break and try again
- At least one study showed that over half of the people who had to stop taking a statin due to side effects were about to successfully tolerate the same or another statin.
Do statins cause diabetes?
Another potential side effect of statin drugs includes blood sugar elevation.
Some people experience a slight increase in blood sugar, which for healthy individuals is often irrelevant. If a person was already overweight and pre-diabetic, the increase can be more concerning and might hasten their conversion to type 2 diabetes.
An interesting truth about statins, however, is that they are highly recommended to reduce heart attack, stroke, and death in patients with diabetes–regardless of cholesterol!
Do statins cause dementia?
There are some reports of a mild, transient decrease in cognition when starting a statin. A negative effect on cognition and dementia has not been proven. When these changes are reported, they are often self-limiting and described as feeling “fuzzy”. On the other hand, the ability of statins to prevent hardening and narrowing of the arteries can actually help prevent dementia given that vascular disease is a leading cause of the same.
Natural Alternatives to Statins
Some patients prefer to take a more natural approach and choose to treat their high cholesterol with red yeast rice. The reason this supplement can work is that the active ingredient is a statin–lovastatin! Lovastatin is also naturally found in oyster mushrooms.
Of note, the US Food and Drug Administration (FDA) actually doesn’t allow lovastatin-containing red yeast rice products on the US market. Patients should exercise caution when purchasing supplements online as they could contain variable amounts of lovastatin. Such products are not regulated by the FDA and so they are not bound by the same manufacturing and safety standards.
And without FDA oversight, there’s also no policing of potential contaminates. Some red yeast rice products have been found to have a chemical called citrinin which can cause kidney failure.
So if you do take red yeast rice for cholesterol, you’re essentially taking an unregulated and potentially contaminated statin that wasn’t legal to sell in the first place! Not to mention that any lovastatin in red yeast rice (also known as monacolin K) would produce the exact same side effects as the prescription version.
Other Advantages of Statins
One of the most interesting truths about statin drugs is actually not related to cholesterol at all. Statins are anti-inflammatories. This is called a pleiotropic effect, i.e. a beneficial effect outside of what was expected. They are also believed to stabilize fatty plaques within blood vessels and normalize the function of the cells that line those blood vessels.
One of the largest clinical studies that validated these extra benefits of statins was titled Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin, aka the JUPITER trials.
The JUPITER trial was a randomized double-blind placebo-controlled study that began in 2003. Researchers enrolled 17,800 people without evidence of heart disease but who had high levels of inflammation as measured by a blood test called high sensitivity C-reactive protein (hsCRP).
Ultimately, those taking the statin (rosuvastatin in this case) had lower levels of bad LDL cholesterol and hsCRP as well as fewer heart attacks, strokes, and death during the study’s one-year time period. JUPITER was far from perfect, however, and actually received some negative press given concerns of commercial bias.
Truth never lost ground by inquiry. –William Penn
But JUPITER wasn’t the only study to demonstrate the pleiotropic effects of statins. A British study evaluated 20,000 individuals, this time considered to be high-risk meaning that they had to have at least one of the following criteria:
- Heart disease
- Hypertension or high blood pressure
Not only did taking simvastatin, in this case, lower the number of heart attacks and stroke but it saved lives.
Statin Drugs in 2023
Since Dr. Endo’s discovery of lovastatin over 30 years ago, 6 other statins have become available on the US market:
- Fluvastatin (Lescol®)
- Pravastatin (Pravachol®)
- Atorvastatin (Lipitor®)
- Simvastatin (Zocor®)
- Rosuvastatin (Crestor®)
- Pitavastatin (Livalo®)
The most effective statin drug is rosuvastatin with a 40 mg dose lowering LDL-C (the bad cholesterol) by 55%. It also raised the good HDL cholesterol by 10% and lowered triglycerides by 28%.
Simvastatin and pravastatin hold the distinguished designation of being the most tolerable statins with the fewest side effects. So are statins really worth taking? Yes. They will very likely extend your life.
Frequently Asked Questions about Statins
Can I drink alcohol while taking a statin?
According to a 2014 article in the Journal of Lipidology, both alcohol and statin drugs are metabolized through the liver which increases the risk of an adverse reaction. While no official recommendations are available, however, 2 alcoholic drinks in a 24-hour period (considered a moderate amount for men) “offer less concern for pharmacokinetic and pharmacodynamic effects than larger amounts.” In other words, any more than the maximum recommended amounts could spell trouble.
How do statin drugs work?
Statins primarily work by reducing LDL-C (bad cholesterol) which contributes to the development of plaque in the blood vessels. They are also believed to stabilize existing plaques and reduce inflammation.
Will a statin make me gain weight?
One analysis has shown that people who take statin drugs tend to increase their fat intake in addition to consuming more calories overall. Weight gain ensues and BMI increases. So do statins cause weight gain? No, overeating causes weight gain. This study showed that by taking statins, some patients may have developed a false sense of security thinking the medication could undo the effects of a poor lifestyle.
This 2018 article echoes the previous one and asserts that statin use contributes to weight gain by possibly undermining a patient’s motivation to make healthy choices. Researchers add, however, that the hormone that helps a person feel full, leptin, may be decreased in statin users. This may be another mechanism by which statins contribute to weight gain.
What happens if you stop taking a statin?
Many patients choose to stop taking statins for one reason or another. Any improvement in cholesterol reverts back to baseline when this happens. Any side effects such as muscle aches will also resolve. Ezetimibe is a non-statin cholesterol-reducing medication for those for can’t or won’t take a statin. Ezetimibe (Zetia®) reduces the risk of non-fatal heart attack and stroke but has no life-extending effect like statins.
Do statins cause fatigue?
Possibly. A 2012 study sought to answer this exact question and found that two statins (simvastatin and pravastatin) caused changes in energy, most notably in women. Participants rated their perceived levels of energy on a 5-point scale with 0 being no change, +2 meaning much more energy and -2 meaning much less energy. The analysis showed an average reduction of 0.25 points with simvastatin and 0.17 points with pravastatin. This may be statistically significant but unlikely clinically significant.
Can I refuse to take a statin?
Absolutely, but know your risk first. The American College of Cardiology offers a risk assessment tool that can also be used to determine the impact of various treatments, including statins.
Should I take a statin after age 65?
Possibly. Statin use after age 65 has traditionally been controversial. A 2019 study in the New England Journal of Medicine suggested that aggressive LDL lowering in high-risk elderly patients is beneficial and safe.
This article was medically reviewed by Ben Taylor, PhD, PA-C, DFAAPA
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