statin

Statins Raise Your Blood Sugar. Is It a Problem?

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A massive percentage of people with diabetes, both type 1 and type 2, are advised to take statins. These cholesterol-lowering drugs are associated with very significant health benefits, particularly a lower risk of early death from cardiovascular disease.

But did you know that statins — the widely-prescribed cholesterol drugs — can cause blood sugar spikes? For some people, they may even trigger the development of type 2 diabetes, a condition sometimes called statin-induced diabetes.

This article will discuss the risk of statin-induced hyperglycemia and diabetes — and why health authorities believe that the benefits of statins still outweigh the risks. 

The Benefits of Statins

If you have diabetes, you’re probably supposed to be taking a statin, too. Diabetes authorities recommend that a very high percentage of people with diabetes, whether type 1 or type 2, should be on statin therapy, including everyone over the age of 40. (An online risk calculator can show you your own recommendations.)

Statins are primarily intended to lower LDL cholesterol, the so-called “bad cholesterol” that is believed to clog our arteries and lead to heart attack and stroke. But many large and rigorous trials have found that statins have additional benefits that can’t be explained by improvements in LDL levels, and that the drugs even confer major benefits to people who do not have elevated LDL to start with.

The CARDS trial, for example, was terminated two years ahead of time because the statin intervention was found to be so effective. Adults with type 2 diabetes using a statin were 27 percent less likely to die during the course of the trial, and 37 percent less likely to experience a major cardiovascular event. The JUPITER trial evaluated statins in patients with inflammation but normal LDL cholesterol. This trial was also stopped early because it was so effective: Participants taking a statin were 20 percent less likely to die, and 44 percent less likely to have any vascular event.

Though medical authorities almost universally endorse the use of statins, there is good evidence that these drugs can have an unexpected negative metabolic effect: they provoke insulin resistance and higher blood sugar. And it pushes some people over the edge from prediabetes to full-blown type 2 diabetes.

 Statins, Insulin Resistance, and High Blood Sugar

Despite the impressive evidence in favor of statin use, there’s one big red flag for people with diabetes: Statins are known to increase insulin resistance, leading to higher blood sugar levels.

For over a decade, the Food and Drug Administration has required a warning on statin labels stating that the drugs “may raise levels of blood sugar.” Multiple other studies in the years since have found similar effects:

  • A 2016 study of patients with type 1 diabetes found that statin use “deteriorates insulin sensitivity.”
  • A 2021 investigation found that “statin users had a higher likelihood of insulin treatment initiation, developing significant hyperglycemia, experiencing acute glycemic complications, and being prescribed an increased number of glucose-lowering medication classes.”

 If you already have diabetes of any type, statins can make your glucose management more challenging. Many studies, such as a 2018 meta-analysis, have pointed to increased A1C and fasting blood glucose levels, and the Diabetes Daily forums have many reports of people experiencing this side effect. A 2021 review which considered multiple meta-analyses concluded that “there is a small aggregate effect of statins in increasing hemoglobin A1C. This effect may be greatest with high-dose atorvastatin and least with pitavastatin.”

One thing is clear: Despite some skepticism within the diabetes community, medical authorities are unanimous that the positive health effects of statins outweigh the risks for people with diabetes.

That doesn’t mean that you need to accept statin-induced hyperglycemia as a necessary evil. A clinical guideline from the Southern Medical Journal suggests that people with diabetes who are just starting moderate- or high-intensity statin therapy should pay close attention to their blood sugar levels and be prepared to make other changes to their lifestyle or medication to prevent hyperglycemia from worsening. 

Statin-Induced Diabetes

When statins raise blood sugar levels, they will invariably help push some people with prediabetes over the line into overt type 2 diabetes: 

  • An analysis of the JUPITER trial, mentioned above as one of the strongest experiments showing the benefits of statins, also found that trial participants were much more likely to be diagnosed with type 2 diabetes.
  • A diabetes prevention study that evaluated adults at a “high risk” of diabetes found that those who developed type 2 diabetes within a decade were 36 percent more likely to have been prescribed a statin — an association that was not “confounded” by factors like high cholesterol levels.

It’s a surprising relationship, given that statins are otherwise good for your metabolism. A recent review in the Cleveland Clinic Journal of Medicine summarizes some extra details:

  • The risk of statin-induced diabetes is greater with high-intensity statin therapy and larger statin doses.
  • Traditional diabetes risk factors, such as obesity, genetic history, and sedentary lifestyle, also help make statin-induced diabetes more likely.
  • The risk is especially high with the concurrent use of glucocorticoid steroids, which also increase insulin resistance.
  • Atorvastatin (Lipitor) may have a stronger glucose-raising affect than other statins.
  • Pitavastatin (Livalo, Zypitamag) may have a lower risk of increased insulin resistance, though it is also less strongly associated with positive cardiovascular effects.

Very few people are told that they have a specific condition called “statin-induced diabetes” — the condition is treated as if it were identical to other common cases of type 2 diabetes.

In an editorial, Eliot Brinton, MD, considers the clinical implications for people that appear to have cases of statin-induced diabetes. Like other experts, he suggests that “the overall risk-benefit ratio remains strongly in favor of statin therapy,” meaning that hyperglycemia is not alone sufficient reason to stop using statins. But he further argues that we should not simply accept the increased risk of new-onset type 2 diabetes. Instead, clinicians should consider some of the following additional measures to help keep hyperglycemia under control:

  • Diet and lifestyle changes to combat rising blood sugar levels
  • The use of other glucose-lowering medicines
  • A preference for statins that are less likely to trigger insulin resistance, especially pitavastatin
  • Taking a “less is more” approach and not immediately choosing high-intensity or maximally-tolerated statin regimens

The Bottom Line

Statins are almost universally recommended to adults with diabetes because they promise incredible protection from cardiovascular disease. But at the same time, these drugs have a concerning tendency to raise blood sugar levels. In some people, statins can even trigger new cases of type 2 diabetes.

Experts agree that the benefits of statins far outweigh the risks, and that if statins cause a modest increase in your A1C, it’s still worth it for the impressive cardiovascular protection. But that doesn’t mean that you should just accept higher blood sugar levels. If you’re concerned that statins are frustrating your blood sugar management, you can talk to your doctor about switching to a different statin, moderating your dosage, or employing other techniques — including lifestyle changes or extra medication — to help keep your glucose numbers in check.

How statins may fuel your heart’s greatest threat

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Statins, a class of medications primarily prescribed to lower cholesterol levels and promoted as a way to avoid a heart attack, have actually been shown to cause inflammation and other issues in the body, including heart problems – as you’ll soon see.  The most frequently prescribed statins encompass pravastatin (brand name: Pravachol), simvastatin (brand name: Zocor), rosuvastatin (brand name: Crestor), and atorvastatin (brand name: Lipitor).

A recent study published in the Journal of Cardiovascular Pharmacology shows that taking statins might make things worse for people with heart failure by affecting their muscles and gut health, leading to more inflammation.  A previous study featured in Clinical Pharmacology makes an even more concerning point.  The study suggests that statins might have a net negative impact on heart health, challenging the conventional wisdom surrounding their use.

Why statins are no longer worth the risk

Chances are you’ve read or heard about how statins are the most effective means of preventing a heart attack.  Doctors and academicians have lauded statins as the primary line of defense against heart disease, the top cause of death across the globe.  However, the use of statins over a lengthy period appears to accelerate the calcification of the coronary artery instead of safeguarding it.

According to one study, statins are likely to serve as mitochondrial toxins that reduce muscle functionality within the heart and its connecting blood vessels.  The decline in muscle functionality occurs with the reduction of CoQ10, short for coenzyme Q10.  CoQ10 is a natural compound found in the body that is an antioxidant, safeguarding cells from harm and enhancing energy synthesis.

A CoQ10 deficiency hinders the production of ATP (adenosine triphosphate), an essential transporter of cellular energy.  The result is a significant energy reduction that is likely to cause damage to the heart and coronary artery.  The authors of the study linked above believe several years of statin use causes mitochondrial DNA damage over time.

The key takeaway from the study is that statins likely cause the accumulation of arterial calcium by suppressing vitamin K.  Moreover, statins also harm the proteins that transmit selenium, a mineral necessary for optimal heart health.  The study authors also suggest statins might cause calcification through increased inflammation.

The problem lies in the fact that doctors are unwilling to objectively consider the risks posed by statins.  An unbiased examination of the data shows statins play a part in causing heart failure.  The startling truth that every heart patient should be aware of is that between 70% and 90% of cardiologists accept financial compensation for prescribing statins.

Solutions to support heart health naturally

Improving heart health is as simple as exercising for 30 minutes per day.  Take a 30-minute daily walk, play some pickleball, or just dance, and you’ll build momentum toward a healthier heart.  Even a moderate amount of strength training or gardening work can condition your heart muscle.  And, finally, in terms of exercise for those people low in energy (to start) … try some deep breathing exercises – several times per day – to reduce blood pressure and improve heart health.

Increase your intake of organic foods and beverages with antioxidants, and you’ll also minimize the chances of blood clots and reduce excessive cholesterol levels and oxidative stress.

Mind the quantity of food you consume.  Never let your eyes be bigger than your stomach.  Plus, a very important “pro tip:” minimize your exposure to wireless radiation from mobile devices to reduce the risk of irregular or rapid heart beats that can stress the heart muscle.

Betrayed by the pill: How statins may fuel your heart’s greatest threat

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Statins, a class of medications primarily prescribed to lower cholesterol levels and promoted as a way to avoid a heart attack, have actually been shown to cause inflammation and other issues in the body, including heart problems – as you’ll soon see.  The most frequently prescribed statins encompass pravastatin (brand name: Pravachol), simvastatin (brand name: Zocor), rosuvastatin (brand name: Crestor), and atorvastatin (brand name: Lipitor).

A recent study published in the Journal of Cardiovascular Pharmacology shows that taking statins might make things worse for people with heart failure by affecting their muscles and gut health, leading to more inflammation.  A previous study featured in Clinical Pharmacology makes an even more concerning point.  The study suggests that statins might have a net negative impact on heart health, challenging the conventional wisdom surrounding their use.

Why statins are no longer worth the risk

Chances are you’ve read or heard about how statins are the most effective means of preventing a heart attack.  Doctors and academicians have lauded statins as the primary line of defense against heart disease, the top cause of death across the globe.  However, the use of statins over a lengthy period appears to accelerate the calcification of the coronary artery instead of safeguarding it.

According to one study, statins are likely to serve as mitochondrial toxins that reduce muscle functionality within the heart and its connecting blood vessels.  The decline in muscle functionality occurs with the reduction of CoQ10, short for coenzyme Q10.  CoQ10 is a natural compound found in the body that is an antioxidant, safeguarding cells from harm and enhancing energy synthesis.

A CoQ10 deficiency hinders the production of ATP (adenosine triphosphate), an essential transporter of cellular energy.  The result is a significant energy reduction that is likely to cause damage to the heart and coronary artery.  The authors of the study linked above believe several years of statin use causes mitochondrial DNA damage over time.

The key takeaway from the study is that statins likely cause the accumulation of arterial calcium by suppressing vitamin K.  Moreover, statins also harm the proteins that transmit selenium, a mineral necessary for optimal heart health.  The study authors also suggest statins might cause calcification through increased inflammation.

The problem lies in the fact that doctors are unwilling to objectively consider the risks posed by statins.  An unbiased examination of the data shows statins play a part in causing heart failure.  The startling truth that every heart patient should be aware of is that between 70% and 90% of cardiologists accept financial compensation for prescribing statins.

Solutions to support heart health naturally

Improving heart health is as simple as exercising for 30 minutes per day.  Take a 30-minute daily walk, play some pickleball, or just dance, and you’ll build momentum toward a healthier heart.  Even a moderate amount of strength training or gardening work can condition your heart muscle.  And, finally, in terms of exercise for those people low in energy (to start) … try some deep breathing exercises – several times per day – to reduce blood pressure and improve heart health.

Increase your intake of organic foods and beverages with antioxidants, and you’ll also minimize the chances of blood clots and reduce excessive cholesterol levels and oxidative stress.

Mind the quantity of food you consume.  Never let your eyes be bigger than your stomach.  Plus, a very important “pro tip:” minimize your exposure to wireless radiation from mobile devices to reduce the risk of irregular or rapid heart beats that can stress the heart muscle.

Editor’s note: Discover the best ways to naturally reduce the risk of heart disease, own the Cardiovascular Docu-Class created by NaturalHealth365 Programs.

AI identifies reasons for statin nonuse in patients with diabetes at a single center

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Key takeaways:

  • An AI model identified reasons for statin nonuse among patients with diabetes.
  • The most common reasons included statin hesitancy, guideline-discordant practice and clinical inertia.

A deep learning model utilized unstructured electronic health record data to identify specific patient-, physician- and system-level reasons for statin nonuse among patients with diabetes, researchers reported.

Reasons for statin nonuse varied across age, race/ethnicity, insurance and diabetes type, according to the study published in the Journal of the American Heart Association.

Statins_AdobeStock
An AI model identified reasons for statin nonuse among patients with diabetes.
Image: Adobe Stock

“Our data showed gaps and disparities in real-world statin use in individuals with diabetes, and an AI approach can be helpful in assessing complex, unstructured clinical notes to shed light on understanding the reasons behind statin nonuse in a health system,” Ashish Sarraju, MD, former fellow in cardiovascular medicine at Stanford University and current staff cardiologist at Cleveland Clinic, told Healio. “The statin nonuse seen in this study — and a prior study we did with patient with established atherosclerotic CVD — was consistent with what has been described in the literature, so we were not surprised. We knew from prior work that our AI approach performed well with assessing clinical notes, but we were still encouraged by how well it could identify complex reasons for statin nonuse.”

Ashish Sarraju

To test their hypothesis, Sarraju and colleagues developed a deep learning NLP algorithm using Clinical Bidirectional Encoder Representations from Transformers (BERT) to identify statin nonuse and actionable reasons for nonuse among 33,461 patients with diabetes at Stanford Health Care Alliance (mean age, 59 years; 49% women; 36% white).

Accuracy of Clinical BERT

The algorithm’s performance was evaluated against expert clinician review and compared with other NLP approaches.

Sarraju and colleagues observed Clinical BERT successfully identify statin nonuse with an area under receiver operating characteristic curve of 0.99 and patient, clinician and system reasons for statin nonuse with an AUC of 0.9.

The researchers reported that Clinical BERT demonstrated good concordance with expert clinician review and outperformed other NLP approaches.

Overall, 47% of the cohort had no statin prescriptions and 16% were using a statin despite no documented statin prescriptions.

Researchers reported that statin hesitancy (19%), guideline-discordant practice (19%) and clinical inertia (18%) were more common compared with side effects and/or contraindications (12%) as the reason for statin nonuse.

Specific reasons for statin nonuse

Reasons for nonuse varied by age, race/ethnicity, insurance and diabetes type, according to the study.

Patients older than 75 years were more likely to experience statin-associated side effects and/or contraindications than statin hesitancy, clinical inertia or discordant practice compared with younger patients (P < .05).

Hispanic individuals were most likely to experience guideline-discordant practice compared with most other reasons for statin nonuse (P < .05), whereas Black patients were most likely to experience clinical inertia as their reason (P < .05), according to the study.

Patients with Medicaid insurance were more likely to experience guideline-discordant practice compared with the other reasons for nonuse (P < .05).

Moreover, patients with type 1 diabetes were more likely to experience guideline-discordant practice compared with the other reasons for statin nonuse (P < .05), according to the study.

Fatima Rodriguez

“Like many health systems, Stanford is developing dashboards and decision support tools to ensure that patients are receiving guideline-directed statin therapy,” Fatima Rodriguez, MD, MPH, FACC, FAHA, associate professor of cardiovascular medicine and section chief of preventive cardiology at Stanford University School of Medicine, told Healio. “Still, gaps in use of evidence-based therapies are pervasive. Our study highlights that augmenting structured data in clinical notes can help understand some of the reasons behind these gaps and help develop health-system-level interventions to address them.”

Bempedoic acid an ‘effective alternative’ for statin-intolerant patients: CLEAR Outcomes

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In the CLEAR Outcomes trial, bempedoic acid reduced risk for major CV events by 13% compared with placebo, including a 23% lower risk for MI, among adults with a history of CVD or at high risk deemed statin intolerant.

Bempedoic acid (Nexletol, Esperion Therapeutics) was FDA approved in 2020 for lowering LDL, but the effects of the drug on CV outcomes have not been assessed, according to Steven E. Nissen, MD, MACC, chief academic officer of the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute and the Lewis and Patricia Dickey Chair in Cardiovascular Medicine at Cleveland Clinic and Cardiology Today Editorial Board member.

ACC Convention Center
Bempedoic acid reduced risk for major CV events by 13% vs. placebo, including a 23% lower risk for MI, among adults with a history of CVD or at high risk deemed statin intolerant.

“Statin intolerance is one of the most vexing problems that we face in cardiology, but also in family practice and internal medicine,” Nissen told Healio. “Patients come to see us and have clear indications for treatment with a statin, and they say they cannot tolerate the drugs. We have needed a clear approach that will work.”

Assessing statin intolerant patients

Steven E. Nissen

Nissen and colleagues analyzed data from 13,970 adults from 1,250 sites across 32 countries who were unable or unwilling to take statins owing to unacceptable adverse effects and had or were at high risk for CVD. To enroll, prospective participants needed to sign a statin intolerance confirmation form, stating they were unable to tolerate statins even though they would reduce the person’s risk for MI, stroke or death.

“This is the first trial designed to exclusively enroll statin-intolerant patients,” Nissen said in an interview.

The mean age of participants was 66 years; 48% were women, 91.5% were white and 45% had diabetes. Approximately 30% of participants were high-risk primary prevention and 70% were secondary prevention patients. Baseline statin use for both groups was 22.9%.

Researchers randomly assigned patients to 180 mg oral bempedoic acid once daily (n = 6,992) or placebo (n = 6,978) and followed the cohort for a median of 40.6 months. Mean baseline LDL was 139 mg/dL.

The primary endpoint was a four-component composite of major adverse CV events, defined as CV death, nonfatal MI, nonfatal stroke or coronary revascularization.

The findings were presented at the American College of Cardiology Scientific Session and simultaneously published in The New England Journal of Medicine.

At 6 months, LDL reduction in the bempedoic acid group was a median 29.2 mg/dL lower than in the placebo group; the observed difference was 21.1 percentage points in favor of bempedoic acid.

The incidence of a primary endpoint event was lower with bempedoic acid than with placebo (11.7% vs. 13.3%; HR = 0.87; 95% CI, 0.79-0.96; P = .004). Similarly, incidence of CV death, nonfatal MI and nonfatal stroke was lower with bempedoic acid vs. placebo (HR = 0.85; 95% CI, 0.76-0.96; P = .006), as was fatal or nonfatal MI (HR = 0.77; 95% CI, 0.66-0.91; P = .002) and coronary revascularization (HR = 0.81; 95% CI, 0.72-0.92; P = .001).

Researchers did not observe any significant effect of bempedoic acid on fatal or nonfatal stroke, CV death and death from any cause.

“The results speak for themselves,” Nissen told Healio. “There was a very robust reduction in the primary endpoint. The first three key secondary endpoints were statistically significant. The drug was well tolerated.”

Adverse events minimal

The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid and hepatic-enzyme levels.

“This did not increase the risk for diabetes, which we have seen with statins,” Nissen said.

Nissen said the addition of other therapies, including PCSK9 inhibitors, narrowed the LDL differences between the groups over time.

“We have established that this drug, approved in 2020 to lower LDL, reduces CV morbidity,” Nissen told Healio. “It did not reduce CV mortality; however, none of the contemporary studies have shown a mortality benefit, including the very powerful PCSK9 inhibitors. It is difficult in the contemporary era to show a reduction in death.

“For patients who cannot tolerate guideline-recommended doses of statins that need an LDL reduction, we have established that bempedoic acid is an effective alternative therapy,” Nissen said.

While presenting the findings, Nissen said that management of patients unable or unwilling to take statins represented a “challenging and frustrating” clinical issue — and said bempedoic acid may provide a solution.

“Regardless of whether this problem represents the nocebo effect or actual intolerance, these high-risk patients need effective alternative therapies,” Nissen said during the presentation.

‘Continue efforts’ to provide statins

In a related NEJM editorial, John H. Alexander, MD, MHS, cardiologist and professor of medicine at Duke University School of Medicine and member in the Duke Clinical Research Institute, wrote that the findings of CLEAR Outcomes are compelling and will — and should — increase the use of bempedoic acid in patients with established atherosclerotic vascular disease and in those at high risk for vascular disease who are unable or unwilling to take statins.

“It is premature, however, to consider bempedoic acid as an alternative to statins,” Alexander wrote. “Given the overwhelming evidence of the vascular benefits of statins, clinicians should continue their efforts to prescribe them at the maximum tolerated doses for appropriate patients, including those who may have discontinued statins because of presumed side effects.”

John F. Keaney Jr., MD, professor at the University of Massachusetts Medical School in Worcester, noted in another NEJM editorial that bempedoic acid can also be used as an adjunct to statin and nonstatin therapies to produce an additional 16% to 26% reduction in LDL; however, it is not yet clear to what extent adjunctive bempedoic acid will further reduce risk for CV events.

“This issue can only be addressed with specific trials powered to detect the effect of bempedoic acid on clinical events,” Keaney wrote. “However, at least in statin-intolerant patients, data from the CLEAR Outcomes trial indicate that bempedoic acid may reduce both the LDL cholesterol level and the risk of cardiovascular events.”

References:

Perspective

Howard Weintraub, MD)

Howard Weintraub, MD

This study is relevant and important because it demonstrates the efficacy and safety of a relatively new nonstatin drug that effectively lowers LDL cholesterol, and it is well tolerated by patients who are “statin intolerant.” Further, it shows that when this drug is used in these patients it was able to reduce the frequency of major adverse CV events such as the need for cardiac surgery, fatal heart attacks, CV death and nonfatal stroke.

These findings are significant because they demonstrates that there is a drug that is useful and safe in a population of patients that frequently go untreated. It also demonstrated that even a modest amount of LDL reduction over a 3.5-year period was able to have a very meaningful impact on CV risk. Finally, and very importantly, it was one of the few studies to include a large proportion of women. Women comprised 48% of the participants in this trial, and 46% of the patients had diabetes.

This could be practice changing because many patients are reluctant to use any of the cholesterol-lowering medications due to adverse symptoms with the use of statins. Two important differences were the low incidence of muscle aches and the low incidence of the development of type 2 diabetes. Muscle aches are the most common adverse events from statins, but the development of type 2 diabetes is also reported. There were slightly more patients with elevated liver enzymes and elevations in uric acid were much more frequent.

In this trial, researchers studied patients who have had prior CV events as well as those at increased risk for an event. Both groups saw a meaningful reduction in the combined endpoint. The population of patients who are statin intolerant or perceived as statin intolerant is not a small number of patients. It would be good to have a drug that has been proven in this population but has been shown to reduce events.

There is also the possibility to combine ezetimibe with bempedoic acid. This is available as a single pill and has been shown in clinical trials to lower LDL cholesterol by as much as 35% to 38%.

Howard Weintraub, MD

Clinical Director, Center for the Prevention of Cardiovascular Disease

Clinical Professor, Department of Medicine, Leon H. Charney Division of Cardiology

NYU Langone Health

Response to a critique of our statin analysis

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By Maryanne Demasi, PhD, Paula Byrne, PhD, Mark Jones, PhD, Robert DuBroff, MD.

On several occasions, we have been asked to respond to a critique of our 2022 systematic review and meta-analysis on statin trials.

The critique was written by Peter Attia in April 2022, a physician and popular podcaster whose interests lie at the intersection of longevity, lipids and heart disease.

Many of the criticisms in Attia’s article were outside the scope of our research, but given his large social media following, and the many requests for our response, we thought we’d address his main points of concern.

A quick recap

Our study, published in JAMA Internal Medicine, examined 21 statin trials involving 143,532 participants and found:

  • No consistent relationship between lowering LDL-Cholesterol (LDL-C) and death, heart attack or stroke, following statin therapy.
  • After statin therapy, the relative risk reductions for death, heart attack and stroke were 9%, 29%, and 14% respectively.
  • The corresponding absolute risk reductions were 0.8%, 1.3% and 0.4% (see graph).
  • The benefits of statins were minimal, and most of the trial participants who took statins, derived no clinical benefit.

Our response to Attia

First, Attia suggests our study doesn’t justify a more judicious approach to statin prescribing, and raises concerns that the coverage in the press could’ve prompted people to stop taking their statins.

… the data from this study do not provide justification for such revision, despite rampant – and potentially deadly – insinuations to the contrary in popular press and social media.

While we cannot control press coverage, the central point of our study was clear — too often, statin advocates will communicate a drug’s relative risk reduction (impressive number), without quoting the absolute risk reduction (trivial number), a practise we consider unethical.

Patients need transparent communication of the relative and absolute risk reduction when being informed about the benefits and harms of statins. This is crucial for patient autonomy, informed consent, and shared decision-making in the doctor-patient relationship.

Second, Attia says we “chose” LDL-C as the focus of our analysis.

Byrne et al. chose to use LDL-C as the relevant variable for mechanistically linking statin efficacy to clinical outcomes, yet LDL-C is not an ideal metric for determining the atherogenic risk. 
….either apoB or non-HDL-C would do so more accurately, yet neither of these preferred metrics was included in the analysis conducted by Byrne and her colleagues

However, LDL-C was the metric used in the design of the 21 statin trials we analysed.  Attia suggests that apoB or non-HDL-C are better indicators of heart disease, but few of the original statin trials reported apoB or non-HDL, so that analysis would not have been possible.

It’s useful to note that LDL-C is the metric usually used in cardiovascular “risk calculators” and to justify statin treatment in professional guidelines for doctors. 

For example, the American Heart Association guidelines say that “LDL-C is the primary cause of atherosclerosis” and promote “the general principle that the lower the better for LDL-C” and that “under certain circumstances the measurement of apo-B may have advantages….nevertheless… carries extra expense, and it’s measurement in some laboratories may not be reliable.”

Third, Attia’s critique pointed out that our study analysed the benefits of statins for an average duration of 4.4 years.

This duration is almost certainly too short to show the full potential effect of LDL-C reductions on CV risk and mortality.

We agree that the duration was short, but the original trials themselves were short.  While we excluded trials in our analysis that were shorter than one year, most of the statin trials, particularly in the later decades, were less than 5 years in duration.

Interestingly, Attia points to studies using Mendelian randomisation as a way of determining the long-term benefits of statin therapy. These complex studies focus on genetic differences in markers of LDL-C that are apparent at birth, rather than treatment induced reductions in actual LDL-C that begin in later life.

If an individual born with a genetic metabolic defect is identified and enrolled into such a study as an adult, we’d have no means of identifying other individuals with the same genetic defect who didn’t survive into adulthood.  This is a clear example of selection bias.  Moreover, we’d have no idea what clinical events took place before enrolment. It’s like conducting a randomised controlled trial lasting 50 years but ignoring the clinical data acquired during the first 45 years of the trial.

Attia argues that if the treatment duration is too short, then the only way to detect a significant effect on mortality is to examine studies with a large magnitude in LDL-C reduction. However, we found some statin trials, with the greatest LDL-C reduction (AURORA and CORONA), reported no clinical or survival benefit.

He cites the FOURIER trial as evidence.

(See for example the FOURIER trial on combined evolocumab and statin treatment), and they show strong causal associations between LDL-lowering treatment and CV events and mortality.

However, the FOURIER trial did not show a mortality benefit. In fact, there were more cardiovascular deaths and total deaths in the group taking the PCSK9 inhibitors compared to placebo, albeit not statistically significant. 

doi: 10.1056/NEJMoa1615664

Notably, the FOURIER trial is now being questioned by researchers who “reanalysed” the data, and found some deaths may have been misclassified. These authors concluded that the potential harm from the treatment is higher than initially reported. 

Additionally, a systematic review and meta-analyses of 54 trials using PCSK9 inhibitors, published in BMJ Heart, reported no reduction in total mortality or cardiac deaths despite dramatic reductions in LDL-C.

The problem with assuming that the benefits of statins continue to accumulate over decades, is that it ignores the fact that statin harms also accumulate — especially if the harms take years to manifest e.g. cognitive decline and diabetes mellitus.

Fourth, Attia points to a study to support the “very strong associations between LDL-C and risk of CV [cardiovascular] events.”

He cites a study that assessed CV events using a “composite of cardiovascular death, nonfatal myocardial infarction, or coronary revascularization.” However, this overlooks the main strength of our analysis. 

We avoided using a composite endpoint because it mixes objective outcomes (death, heart attack and stroke), with subjective outcomes (hospital admissions, angina, and revascularisations). 

We focused on hard outcomes only, making our study robust and less prone to bias.

Recently, our own findings were confirmed by a meta-analysis of 60 randomised controlled trials of statins, PCSK9 inhibitors and ezetimibe, which found no association between the degree of LDL-C reduction and cardiovascular or total mortality.

doc: 10.1097/FJC.0000000000001345 — A horizontal line indicates the size of mortality benefit is not associated with the amount of LDL-C reduction

Finally, Attia says that the article “hasn’t shaken my faith in statins” but we have put faith aside and focused on the data.

The vast majority of these trials are funded by the drug industry, and have been carried out during an era with little regulatory oversight and accountability.

Further, statin manufacturers and a group of researchers at Oxford University remain guardians of the individual participant data, and refuse access to outside researchers for independent scrutiny. 

Statin use in older adults linked to lower risk for parkinsonism

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Older adults had a 16% lower risk for developing parkinsonism after taking statins for 6 years compared with those not on statins, a report published in Neurology showed.

Shahram Oveisgharan, MD, assistant professor of neurological sciences at Rush Medical College in Chicago, and colleagues assessed 2,841 people (average age, 76 years) who did not have parkinsonism, 936 of whom were taking statins. Researchers monitored participants annually for an average of 6 years to check statin usage and signs of parkinsonism.

Source: Adobe Stock.

At the conclusion of the study, 1,432 people (50%) had developed signs of parkinsonism. Of the 936 who were taking statins, 418 people (45%) had developed parkinsonism compared with 1,014 of 1,905 (53%) who were not taking statins.

“Our results suggest people using statins may have a lower risk of parkinsonism, and that may be partly caused by the protective effect statins may have on arteries in the brain,” Oveisgharan said in a press release from the American Academy of Neurology. “Our results are exciting, because movement problems in older adults that come under the umbrella of parkinsonism are common, often debilitating and generally untreatable.”

Further, about 79% of participants on statins were taking moderate or high intensity doses. Those taking higher intensity doses had a 7% lower risk for developing parkinsonism vs. those taking low intensity doses.

Researchers also noted that 1,044 participants died during the study, and post-mortem examination of their brains revealed that those taking statins had 37% reduced odds of atherosclerosis compared with those who had not been taking statins.

“More research is needed, but statins could be a therapeutic option in the future to help reduce the effects of parkinsonism in the general population of older adults, not just people with high cholesterol or who are at risk for stroke,” Oveisgharan said. “At a minimum, our study suggests brain scans or vascular testing may be beneficial for older adults who show signs of parkinsonism but don’t have classic signs of Parkinson’s disease or do not respond to Parkinson’s disease medications.”

GAUSS: PCSK9 antibody reduced LDL in statin-intolerant patients

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Patients at CV risk who are unable to tolerate effective doses of statins experienced reductions in LDL levels of up to 51% with AMG 145, an investigational, anti-PCSK9 antibody, Evan A. Stein, MD, reported here.

The GAUSS study was initiated to test the safety, tolerability and efficacy of subcutaneous AMG145 (Amgen, Inc.), which binds to PCSK9 in the circulation and blocks its interaction with the LDL receptor and thus increases cholesterol removal from the blood stream. Its use was compared with ezetimibe (Zetia, Merck) in statin-intolerant patients at high and moderate CV risk.

The 12-week, randomized, double blind, controlled, dose-ranging study was conducted between July 2011 and May 2012 and enrolled 236 patients. Patients were randomly assigned to one of five groups: AMG145 280 mg, 350 mg or 420 mg alone; AMG 145 420 mg plus 10 mg ezetimibe; or 10 mg ezetimibe plus placebo. AMG 145 and placebo were administered subcutaneously every 4 weeks.

At 12 weeks, mean LDL, measured by ultracentrifugation, decreased 41% for patients assigned AMG 145 280 mg; 43% for AMG 145 350 mg; 51% for AMG 145 420 mg; 63% for AMG 145 420 mg plus ezetimibe; and 15% for placebo plus ezetimibe (P<.001 vs. placebo and ezetimibe).

Evan Stein

Evan A. Stein

Sixty-one percent of patients assigned AMG 145 420 mg achieved an LDL goal of <100 mg/dL and up to 29% reached <70 mg/dL. When combined with ezetimibe, 90% of patients reached the goal of <100 mg/dL and 62% reached <70 mg/dL, according to Stein, from the Metabolic and Atherosclerosis Research Center in Cincinnati, Ohio.

Data also demonstrated benefits in total cholesterol, non-HDL, lipoprotein(a), apolipoprotein B, and the ratios of total cholesterol/HDL and ApoB/ApoA1. AMG 145 alone or with ezetimibe increased HDL modestly, from 6% to 12%, compared with a 1% decrease with ezetimibe alone (P<.001). Small, nonsignificant reductions in triglycerides and VLDL were observed with AMG 145 compared with ezetimibe alone. Free PCSK9 levels declined by 48% from baseline to 12 weeks with AMG 145 and by 2% with ezetimibe alone, according to a press release.

Myalgia was the most common treatment-emergent adverse event during the study. Other adverse events included nasopharyngitis, nausea and fatigue. Overall, the drug was well tolerated and efficacious, with or without ezetimibe, Stein said. However, larger studies are needed to confirm these findings, he added.

The mean age of patients in the GAUSS study was 62 years. Sixty-four percent were women. Mean baseline LDL level was 193 mg/dL. – by Samantha Costa

For more information:

Stein E. Late breaking clinical trials: Novel treatments for managing lipid disorders. Presented at: the American Heart Association Scientific Sessions; Nov. 3-7, 2012; Los Angeles.

Sullivan D. JAMA. 2012;doi:10.1001/jama.2012.25790.

Disclosure: Stein reports being a paid consultant for Amgen and Regeneron-Sanofi.

PERSPECTIVE

BACK TO TOP Peter W.F. Wilson, MD)

Peter W.F. Wilson, MD

PCSK9 is a chaperone that affects the efficacy of LDL receptors. Its role has been highlighted over the last 5 to 10 years, and already we have treatment modalities based on this newly described molecular science. The GAUSS study enrolled adults who did not tolerate statins very well and the participants received subcutaneous injections every 4 weeks of an antibody to PCSK9.

These molecules are of special interest for use as single pharmacologic agents or in combination with other lipid medications to lower LDL. Efficacy of the medication to lower LDL and prevent CVD as well as more information concerning safety of the treatment over longer study intervals are needed.

Peter W.F. Wilson, MD

Atlanta VA Medical Center and

Emory Clinical Cardiovascular Research Institute

Endocrine Today Editorial Board Member

Statin Users, CoQ10 Is Your New Best Friend

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Statin Users, CoQ10 Is Your New Best Friend

Following your doctor prescribed cholesterol-lowering regimen that may include eating healthy, exercising regularly, and taking cholesterol medication such as statins can help keep your cholesterol in check.

However, it’s a bit of a double-edged sword. While statins help to keep your cholesterol levels under control, they can also deplete your body of essential compounds and chemicals that keep the body running smoothly.

More importantly, if you have high cholesterol and are currently taking statin medication, you run the risk of significantly lowering your normal CoQ10 levels, something that could compromise your normal body functions.

According to the University of Maryland Medical Center (UMMC), there is no doubt that statins will “reduce the natural levels of CoQ10 in the body.” In fact, it has been shown that statins can lower CoQ10 levels by up to 40%. This could potentially complicate other health issues and leave you vulnerable to side effects from your prescribed statins.

There is some good news, however. The UMMC reports that “taking CoQ10 supplements might help increase levels in the body and reduce problems.” It further suggests that CoQ10 may support healthy cardiovascular function – something worth considering, especially if you have a history of heart disease in your family.

What is CoQ10?

The term may look like something off the molecular chart from your high school science class, but coenzyme Q10 is the only name we have to describe this essential antioxidant.

What does it actually do, though?

You could say that CoQ10 is a bright spark in the tinderbox, as it gets everything fired up. From vital organs to muscles, you’ll find CoQ10 in every cell (did you know that the highest concentrations can be found in your heart, liver, and kidneys?), balancing electrons, producing energy and fighting off free radicals. It’s the life of the party! In essence, it’s an energy-producing coenzyme that keeps your engine running on all cylinders.

The Power Plant of Every Living Cell

It’s hard to imagine our cells busy at work, rushing through our bloodstream to every organ and muscle in the body, repairing, building, and fighting off intruders. It’s a beehive of industry and this requires a lot of energy. This energy is produced by a complex series of biochemical reactions that results in the production of Adenosine triphosphate (ATP), which is the energy currency of the cell.  CoQ10 is essential to this process due to its electron transfer characteristics and is in fact a vital factor for 95% of the overall energy production at the cellular level.

Thanks to CoQ10, this energy breathes life into your body and keeps it functioning optimally. However, when you’re taking statins, CoQ10 levels are significantly lowered.

What Happens When There’s a Shortage of CoQ10?

As you get older, CoQ10 levels naturally decline and researchers have identified  CoQ10 deficiency as a contributing factor to many health conditions.  Heart disease is probably the most common condition that can be affected by a CoQ10 deficiency, and this includes heart failure, angina, high blood pressure, high cholesterol, and cardiovascular disease. CoQ10 is often recommended by general practitioners and cardiologists alike as a dietary supplement to help assure adequate levels of this coenzyme, especially if you’ve been prescribed statins. It’s has also proven to be an effective after-care supplement for heart failure, heart surgery, and chemotherapy.

CoQ10 is found in a bunch of foods like meat, fish, and whole grains. In a healthy, balanced diet, it should be in adequate supply. However, certain diseases like diabetes, Parkinson’s, and heart disease, as well as drugs like statins can diminish your natural CoQ10 levels considerably. In these instances, the best way to return to normal levels is for you to supplement your diet with CoQ10.

Your organs require huge amounts of CoQ10 to carry out their daily functions. So you can understand how vital this antioxidant is to ensure their health. It’s also a critical component in regulating blood sugar levels and is often also recommended to diabetic patients. Because of how essential it is for energy production and its characteristics as a powerful antioxidant, CoQ10 supplementation is regularly recommended for people with cancer, muscular dystrophy, and periodontal disease.

Is CoQ10 Good for Muscle Pain Caused by Statins?

CoQ10 is in hot demand by the body, as its role is critical in maintaining the overall health of your body. Your organs rely on it, and so too do your muscles. In fact, they can’t function without it.

During any given day, your muscle fibers break down and rebuild in order to get stronger. It’s a bit like housekeeping. Old muscle cells are swept away, with the arrival of fresh cells that are brimming with life.

Deep inside these muscle fibers, you’ll find CoQ10 delivering fresh energy stores to cells in need, as well as warding off intruders. But when levels of CoQ10 are compromised by statins, proper muscle function can be  impaired, and the whole process begins to collapse. The result is muscle pain and joint stiffness – one of the common side effects of statins. Muscle soreness can seriously affect your mobility, not to mention, your quality of life. It also increases your risk of falling, as it leaves you unsteady on your feet.

According to a study published in the American Journal of Cardiology, CoQ10 can help alleviate muscle pain and joint discomfort brought on by statin drugs:

“Results suggest that coenzyme Q10 supplementation may decrease muscle pain associated with statin treatment. Thus, coenzyme Q10 supplementation may offer an alternative to stopping treatment with these vital drugs” – American Journal of Cardiology

Not only is CoQ10 essential in maintaining heart and organ health, it is also instrumental in the proper functioning of your muscles. And one of the secrets to longevity and quality of life is strong muscles.

CoQ10 And Statins – It Makes Sense to Supplement with CoQ10

This vital coenzyme is so essential to the body that you’ll notice immediately if you’re in short supply. Because statins can rob your body of this vital component, it makes sense to supplement your diet with CoQ10. There’s also the added health benefit of its anti-aging, antioxidant properties that help to prevent free radicals from damaging your tissues.

Talk to your doctor to see if CoQ10 is right for you, especially if you’re currently taking statins. It’ll make all the difference to your quality of life.

 

COQ10 SOURCES & REFERENCES

Coenzyme Q10: University of Maryland Medical Centerhttp://umm.edu/health/medical/altmed/supplement/coenzyme-q10

Coenzyme Q10 (CoQ10) : In Depth; National Center for Complementary and Integrative Health

https://nccih.nih.gov/health/supplements/coq10

CoQ10 and Statins: What You Need To Know : Healthline

http://www.healthline.com/health/coq10-and-statins#Overview1

CoEnzyme Q10, An Overview : Web MD

http://www.webmd.com/heart-disease/heart-failure/tc/coenzyme-q10-topic-overview

Effect of coenzyme q10 on myopathic symptoms in patients treated with statins:

American Journal of Cardiology

Ghirlanda G., Oradei A., Manto A., et al. Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol. 1993;33(3):226–229.

Statin Users, CoQ10 Is Your New Best Friend

Posted by

0


Statin Users, CoQ10 Is Your New Best Friend

Following your doctor prescribed cholesterol-lowering regimen that may include eating healthy, exercising regularly, and taking cholesterol medication such as statins can help keep your cholesterol in check.

However, it’s a bit of a double-edged sword. While statins help to keep your cholesterol levels under control, they can also deplete your body of essential compounds and chemicals that keep the body running smoothly.

More importantly, if you have high cholesterol and are currently taking statin medication, you run the risk of significantly lowering your normal CoQ10 levels, something that could compromise your normal body functions.

According to the University of Maryland Medical Center (UMMC), there is no doubt that statins will “reduce the natural levels of CoQ10 in the body.” In fact, it has been shown that statins can lower CoQ10 levels by up to 40%. This could potentially complicate other health issues and leave you vulnerable to side effects from your prescribed statins.

There is some good news, however. The UMMC reports that “taking CoQ10 supplements might help increase levels in the body and reduce problems.” It further suggests that CoQ10 may support healthy cardiovascular function – something worth considering, especially if you have a history of heart disease in your family.

What is CoQ10?

The term may look like something off the molecular chart from your high school science class, but coenzyme Q10 is the only name we have to describe this essential antioxidant.

What does it actually do, though?

You could say that CoQ10 is a bright spark in the tinderbox, as it gets everything fired up. From vital organs to muscles, you’ll find CoQ10 in every cell (did you know that the highest concentrations can be found in your heart, liver, and kidneys?), balancing electrons, producing energy and fighting off free radicals. It’s the life of the party! In essence, it’s an energy-producing coenzyme that keeps your engine running on all cylinders.

The Power Plant of Every Living Cell

It’s hard to imagine our cells busy at work, rushing through our bloodstream to every organ and muscle in the body, repairing, building, and fighting off intruders. It’s a beehive of industry and this requires a lot of energy. This energy is produced by a complex series of biochemical reactions that results in the production of Adenosine triphosphate (ATP), which is the energy currency of the cell.  CoQ10 is essential to this process due to its electron transfer characteristics and is in fact a vital factor for 95% of the overall energy production at the cellular level.

Thanks to CoQ10, this energy breathes life into your body and keeps it functioning optimally. However, when you’re taking statins, CoQ10 levels are significantly lowered.

What Happens When There’s a Shortage of CoQ10?

As you get older, CoQ10 levels naturally decline and researchers have identified  CoQ10 deficiency as a contributing factor to many health conditions.  Heart disease is probably the most common condition that can be affected by a CoQ10 deficiency, and this includes heart failure, angina, high blood pressure, high cholesterol, and cardiovascular disease. CoQ10 is often recommended by general practitioners and cardiologists alike as a dietary supplement to help assure adequate levels of this coenzyme, especially if you’ve been prescribed statins. It’s has also proven to be an effective after-care supplement for heart failure, heart surgery, and chemotherapy.

CoQ10 is found in a bunch of foods like meat, fish, and whole grains. In a healthy, balanced diet, it should be in adequate supply. However, certain diseases like diabetes, Parkinson’s, and heart disease, as well as drugs like statins can diminish your natural CoQ10 levels considerably. In these instances, the best way to return to normal levels is for you to supplement your diet with CoQ10.

Your organs require huge amounts of CoQ10 to carry out their daily functions. So you can understand how vital this antioxidant is to ensure their health. It’s also a critical component in regulating blood sugar levels and is often also recommended to diabetic patients. Because of how essential it is for energy production and its characteristics as a powerful antioxidant, CoQ10 supplementation is regularly recommended for people with cancer, muscular dystrophy, and periodontal disease.

Is CoQ10 Good for Muscle Pain Caused by Statins?

CoQ10 is in hot demand by the body, as its role is critical in maintaining the overall health of your body. Your organs rely on it, and so too do your muscles. In fact, they can’t function without it.

During any given day, your muscle fibers break down and rebuild in order to get stronger. It’s a bit like housekeeping. Old muscle cells are swept away, with the arrival of fresh cells that are brimming with life.

Deep inside these muscle fibers, you’ll find CoQ10 delivering fresh energy stores to cells in need, as well as warding off intruders. But when levels of CoQ10 are compromised by statins, proper muscle function can be  impaired, and the whole process begins to collapse. The result is muscle pain and joint stiffness – one of the common side effects of statins. Muscle soreness can seriously affect your mobility, not to mention, your quality of life. It also increases your risk of falling, as it leaves you unsteady on your feet.

According to a study published in the American Journal of Cardiology, CoQ10 can help alleviate muscle pain and joint discomfort brought on by statin drugs:

“Results suggest that coenzyme Q10 supplementation may decrease muscle pain associated with statin treatment. Thus, coenzyme Q10 supplementation may offer an alternative to stopping treatment with these vital drugs” – American Journal of Cardiology

Not only is CoQ10 essential in maintaining heart and organ health, it is also instrumental in the proper functioning of your muscles. And one of the secrets to longevity and quality of life is strong muscles.

CoQ10 And Statins – It Makes Sense to Supplement with CoQ10

This vital coenzyme is so essential to the body that you’ll notice immediately if you’re in short supply. Because statins can rob your body of this vital component, it makes sense to supplement your diet with CoQ10. There’s also the added health benefit of its anti-aging, antioxidant properties that help to prevent free radicals from damaging your tissues.

Talk to your doctor to see if CoQ10 is right for you, especially if you’re currently taking statins. It’ll make all the difference to your quality of life.

 

COQ10 SOURCES & REFERENCES

Coenzyme Q10: University of Maryland Medical Centerhttp://umm.edu/health/medical/altmed/supplement/coenzyme-q10

Coenzyme Q10 (CoQ10) : In Depth; National Center for Complementary and Integrative Health

https://nccih.nih.gov/health/supplements/coq10

CoQ10 and Statins: What You Need To Know : Healthline

http://www.healthline.com/health/coq10-and-statins#Overview1

CoEnzyme Q10, An Overview : Web MD

http://www.webmd.com/heart-disease/heart-failure/tc/coenzyme-q10-topic-overview

Effect of coenzyme q10 on myopathic symptoms in patients treated with statins:

American Journal of Cardiology

Ghirlanda G., Oradei A., Manto A., et al. Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol. 1993;33(3):226–229.