Are The Benefits Of Statins Greater Than The Risks?
Medical science is not static. An evolving amount of clinical data can help us rethink and re-evaluate our disease prevention, diagnosis and treatment approach. If there are clinical recommendations to change medication, it is seldom because the old data is inaccurate. Instead, new information prompts healthcare providers to rethink their approach.
Studies on the same drug, conducted separately for decades, may produce different results as the health profile of adults has changed over time. Today, obesity, high blood pressure, diabetes, high cholesterol, and inactive lifestyles are more common in patients than 30 years ago. In addition, patients may take medications that didn’t exist 10 or 20 years ago. The changing clinical profile of our population will affect the risk-benefit balance of any drug as a treatment in a clinical trial. This is why clinical recommendations regarding the use of the drug may change, even if the drug has existed for decades.
Statin Medication Overview
Changes in clinical indications for statin use indicate changes in use patterns. In 1987, lovastatin was approved for use by the FDA. Since then, other statin drugs have been approved by the FDA, including pitavastatin, rosuvastatin, atorvastatin, simvastatin, pravastatin and fluvastatin.
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$37.98 Add to cartIn the early years of statins drugs, patients with atherosclerotic cardiovascular disease (ASCVD) who had already suffered a heart attack or stroke, undergone bypass or stent surgery were prescribed statin medications in combination with exercise and following a healthy diet in order to lower LDL (bad or undesirable) cholesterol. Subsequent studies of this patient population (those with ASCVD) showed a significant reduction in additional cardiac events or death.
Over time, further evidence from clinical trials prompted the recommendation that statin drugs be used for the primary prevention of ASCVD. This recommendation is based on data from clinical trials showing a reduction in the incidence of first heart attack or first stroke in patients at high risk of developing these events due to the presence of multiple cardiovascular risk factors, such as diabetes, hypertension, smoking, very high LDL cholesterol and significant coronary artery calcification shown on CT scan.
It isn’t surprising that statin drugs are one of the most commonly prescribed types of drugs in the United States, as ASCVD is the leading cause of death in adults.
In general, newer statin drugs have increased potency, leading to more significant reductions in LDL cholesterol. Previously, statin doses were chosen to achieve a specific LDL target, such as <130 mg/dl or <70 mg/dl. Newer guidelines place more emphasis on statin dosing intensity (medium versus high-intensity dosing) than on post-treatment LDL cholesterol level. The intensity of a single dose of statin medication is a double-edged sword – the stronger the medication, the greater the reduction in LDL, but also the greater the risk of side effects.
Possible Statin Side Effects
Adults, whether taking statins or not, recognize that muscle pain is a possible side effect of taking statins. This has become a common topic in health reports as higher-intensity statins are prescribed more often. Also, it’s important to consider that patients sometimes leave the office with a prescription for a statin drug and a prescription for exercise. As they begin exercising and also taking the statin medication, it can be difficult to distinguish between muscle soreness due to statin medications or muscle soreness due to a new exercise program.
There is a trial and error method to determine if reducing the dose or switching to a different brand of statin will reduce muscle soreness. People are different. Some people can run marathons on high-dose statins, while others have so much muscle soreness on a low-dose statin that it’s difficult to stand up when they’ve been sitting. Due to the robust reduction of LDL by statin drugs, researchers are actively trying to figure out the physiological mechanism of this side effect so they can find a way to prevent it.
Statin Medications and Muscle Soreness Risk
In recent decades, studies conducted to understand the relationship between muscle pain side effects and statin use have sparked much discussion about the “nocebo effect” of statin drugs and introduced many health care providers to the concept of “n-of-1” trials.
A nocebo effect is when a person’s negative expectations about treatment result in more negative side effects than if the patient had neutral or positive expectations. This is the opposite of the “placebo effect” – where we have more positive outcomes when we believe the treatment will make us feel better.
The nocebo effect has been documented in many studies on statin use. In a study of more than 10,000 patients taking statin or placebo in a blind phase (where patients did not know if they received a statin or placebo), the number of symptoms in both groups was similar. However, when patients found that they were taking a statin, muscle-related symptoms were reported in this group.
While health care providers may recommend changing the dose or brand of a statin to relieve muscle symptoms, doing so does not entirely eliminate the nocebo effect. The only way to completely eliminate the nocebo effect is to prevent the patient from knowing what he is taking, which is the basic idea of ”n-of-1″ trials.
The n-of-1 statin studies are simple crossover studies in which the order of administration of statin medication or a placebo is random. In one study, researchers at primary care clinics enrolled 200 participants who discontinued statin treatment due to muscle symptoms. Participants were randomized to a series of six double-blinded treatment phases, each lasting two months in which they received either 20 mg of atorvastatin daily or a placebo. After each two-month period, participants provided symptom scores using a visual analog scale (0-10). As the study was blinded, the participants didn’t know if they were receiving the statin or the placebo during each two-month period. Interestingly, there was no difference in muscle symptom scores between the statin and placebo periods, and the majority of the participants restarted ongoing statin treatment without muscle symptoms.
While muscle symptoms in most patients appear to be caused by the nocebo effect, this does not mean that the patient’s muscle pain is in their head. Their pain is real and can impact their quality of life. The nocebo effect highlights the need for patients and physicians to have candid conversations about concerns associated with statin use so patients can approach statin use with a more optimistic attitude based on the benefits.
Statin Medications and Diabetes Risk
Another potential side effect of statin medication is the effect of statins on the risk of elevated blood sugar (glucose) and the risk of developing diabetes. This is a much more objective side effect that can be detected compared to the symptoms of muscle pain, as this effect is identified by a change in the blood test result (fasting glucose or hemoglobin A1C).
The idea that statin drugs can increase blood sugar levels has gained significant clinical attention following the publication of the JUPITER study (2008). This large study included nearly 18,000 apparently healthy men and women with high c-reactive protein (a blood marker that measures inflammation) and LDL levels below 130 mg /dl. Participants were prescribed a daily high-intensity statin (rosuvastatin) for the primary prevention of ASCVD events. While statin use was associated with a reduced risk of ASCVD, it was also associated with an increased hemoglobin A1C (a blood test used to diagnose prediabetes and diabetes) and a physician-reported diagnosis of diabetes.
A follow-up meta-analysis of 13 statin studies in 2010 (conducted from 1994 to 2009, with at least 1,000 patients and a study duration of more than one year) with a combined total of 91,140 patients showed that statin treatment was associated with a 9 percent increased risk of developing diabetes. In addition, in an analysis of five clinical trials with more than 32,000 participants with previous ASCVD events, experts found that the risk of developing diabetes was slightly higher in high-intensity statin users compared to moderate-intensity statin users. However, the researchers also proved high statin use reduced the incidence of ASCVD events.
An FDA warning was added to statin medications in 2012 that advised some patients may experience an increased risk of high blood sugar and may be diagnosed with type 2 diabetes.
Modifiers of Diabetes Risk With Statin Use
However, not all subsequent clinical studies have shown an increased risk of diabetes. In a large initial primary prevention study of more than 12,000 intermediate-risk patients for ASCVD treated with moderate-intensity statin medication (10 mg rosuvastatin) or placebo, there was a significantly lower risk of cardiovascular events in the statin group, with no increased risk of diabetes.
Why were the results different in different studies? These differences are likely due to the study populations being different. People who previously had a high risk for developing diabetes were also more likely to develop diabetes as a side effect of taking statins.
The risk of developing diabetes over time, separate from the use of statins, is more likely to occur in people with high blood sugar to start with (pre-diabetes glucose 100-126 mg/dl), large waist circumference (high belly fat) body mass index higher than 30 (obesity levels) and high blood triglycerides (an indicator of insulin resistance).
The risk of developing diabetes over time, independent of statin use, is more likely to occur in individuals with risk factors:
Diabetes Risk Factors
|
|
|---|---|
| High Fasting Blood Sugar | Glucose levels of 100-125 mg/dL (or being on medication to treat high blood sugar) |
| Large Waist Circumference | 35 inches or more for women or 40 inches or more for men |
| High Body Mass Index | ≥30.0 kg/m |
| High Blood Triglyceride Levels | 150 mg/dL or higher |
| Low HDL (healthy) cholesterol level | Less than 50 mg/dL for women and less than 40 mg/dL for men |
| High Blood Pressure | 130/85 mmHg or higher (or being on medication to treat high blood pressure) |
| High Fasting Glucose | ≥100 mg/dL or are taking glucose-lower medications |
The presence of these factors also increases the risk of developing diabetes when taking statins. In an analysis of 15,000 patients with known ASCVD who were treated with moderate or high-intensity statins for an average of five years, patients with high blood sugar initially were more likely to develop diabetes using statins than those who had normal blood baseline glucose levels (14 percent vs. 3 percent respectively). Notably, though, the use of statin drugs reduced the risk of heart attack or stroke in all statin-treated patients, even if they developed diabetes during the study.
These findings, which make statin use more likely to be associated with diabetes in patients with risk factors for diabetes, underscore the importance of practicing healthy behaviors to maintain healthy blood sugar levels, waist circumference, and weight. Healthy behaviors include:
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- Get aerobic exercise, 30 minutes per day and 150 minutes per week (or more, in bouts as little as 10 minutes per session) of moderate aerobic exercise such as brisk walking
- Strength train, 2 to 3 times a week, to increase strength, balance, and agility
- Eat a healthy diet
- Don’t smoke or ingest tobacco
- If you drink alcohol, be a light to moderate drinker
Recommended Supplements With Statin Medications
Statin medications can lower Coenzyme Q10 levels, and it’s thought lower CoQ10 levels may lead to muscle aches and pains. Nina Radford, MD, Cardiologist, and Director of Clinical Research at Cooper Clinic, often recommends CoQ10 to patients who suffer from statin medication muscle aches and pains. “Given that CoQ10 is generally safe and well-tolerated, many physicians, including myself, will recommend a trial of CoQ10 in an effort to keep our patients on much-needed statin therapy,” says Radford.
“It is absolutely anecdotal, but I have patients who swear by it and I have patients who did not think it was helpful at all. My goal is to avoid statin discontinuation, so if it works, great. There are rare interactions with other medications such as the blood thinner warfarin and CoQ10. These interactions should be avoided during pregnancy or when breastfeeding, so it’s important to discuss using CoQ10 with your health care provider. From a cardiovascular perspective, it is strongly recommended patients treated with statins also have their vitamin D deficiency treated in an effort to avoid muscle soreness and statin intolerance. Of course, that means they have had their vitamin D levels measured.”
Undeniably, side effects and fear of side effects of statins strongly influence a patient’s decision to stop the statin. In general, half of the patients using statins will stop taking the medication, despite advice from their health care provider. Unfortunately, the decision to discontinue statins early can lead to adverse clinical outcomes in some patients and increase the risk of serious ASCVD events, including death.
It is important to talk to your health care provider about your symptoms and concerns about taking statins rather than simply discontinuing the medication.
Resources
Learn about Reducing Statin Side Effects: Can Supplements Help?
Learn about Berberine and Plant Sterol supplements to lower cholesterol the natural way.
Learn more about Cooper Clinic preventive exams and how an annual exam can help you manage and improve your health.
Learn how a registered dietitian nutritionist can help you with your diet.