Losing Your Mind? It's not the Statins

There does not seem to be a day that I don't wake up in the morning and see some negative press regarding statins. Well yesterday was no exception when on Good Morning America, I once again heard that some "expert" said that statins make women lose their memory. It really is getting ridiculous. It would be nice to hear that statins have changed the face of Cardiovascular disease by reducing morbidity and mortality dramatically. Despite this, we still have a long way to go to eradicate Cardiovascular disease which still remains the number 1 killer of men and women in the United States.

I was planning to write on this topic next week, as I have been really busy seeing patients, but thought I needed to take the time to address the new comments. Like I have said before, the Statin Safety Task Force of the National Lipid Association also formed a Neurology Panel to look at the evidence based literature to assess the effects of statins on the Nervous System.

First of all, there is no evidence that statins are a common or significant cause of peripheral neuropathy. This is supported by the large randomized clinical trials including the Heart Protection Study (HPS) and the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). The HPS was the largest statin trial to date and included 20,536 participants who were followed over a 5 year period. It is always possible that a rare case of peripheral neuropathy could occur but this would most likely represent an idiosyncratic reaction which I talked about in a previous posting.

In regard to the question whether statins impair memory or cognition in some patients, the answer is that there is no evidence of a causal relation between impaired memory and/or cognitive dysfunction. Besides the HPS and PROSPER, two additional studies have specifically evaluated the effect of statin therapy on patients with Alzheimer's disease, a population group at risk for cognitive decline. In one of the trials, there was a statistically significant reduction in the rate of cognitive decline compared with placebo, suggesting a benefit for Atorvastatin in Alzheimer's disease. This is the exact opposite of what I heard this morning.

I think the best way to approach a patient with peripheral neuropathy or impaired cognition while on statins is to first undergo a thorough neurologic exam by a neurologist in an attempt to find a cause. If this is not possible, it is certainly appropriate to stop the statin to see what happens.

Due to the length of time it can take to resolve reversible peripheral neuropathy, the patient should remain off the statin for 6 months. For patients with impaired cognition they should wait about 3 months. If symptoms improve then it is certainly possible that a presumptive diagnosis of being caused by statins can be made.

One might want to consider a different statin, as the benefits of statins in reducing Cardiovascular Morbidity and Mortality have been proven. If the neurologic symptoms do not improve, the problem may be categorized as unrelated to the statin and therapy may want to be restarted based on a risk-benefit analysis.

One must remember that many other causes of impaired cognition and/or peripheral neuropathy in patients taking statins may exist. These include Vascular disease, Diabetes Mellitus, and advancing age. I feel confident in saying that statins do not make women lose their memory.

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• Statins: Heart Health Superstars
• Cholesterol Management: Statins

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Statins and Muscle Pain

I have spent the last 2 weeks answering questions about Vytorin and Zetia after the media caused an inexcusable hysteria that in some way Zetia or any combination which included it was bad. One well-known expert always seems to weigh in on every cholesterol issue and gives the thumbs-up if he was involved in the study and the thumbs-down if he was not.

I can tell you that those of us who practice full time clinical medicine and see patients daily have not altered our prescribing practice on the basis of the ENHANCE study which was strictly an imaging study with no outcome data regarding what the findings actually mean in the patients.

It is a shame that the ASTEROID and METEOR studies involving Crestor, which were also imaging studies but showed a decrease in the plaque burden in the heart arteries(ASTEROID) and a regression in some patients and no progression in others(METEOR) of the same thing that was measured in the ENHANCE study (CIMT or Carotid Intimal Medial Thickness) and generated all the confusion, were not mentioned in the media. The point is that all of these studies are imaging studies and there is no outcome data so I really do not know what any of them mean in a practical sense.

Are statins bad for the muscles?

Once again I will present the evidence-based data, but first, some definitions:

• Myalgia is a non-specific common complaint of muscle ache and there are no abnormalities of the muscle enzyme CPK or CK on a blood test. Myalgia has rarely been examined in clinical trials and it is thought that some type of muscle aches can occur in up to 30% of patients on statins. Unfortunately, many of these patients start a vigorous exercise program at the time they start their statin because they decide it is to "get in shape" and one doesn't know where the orgin of the muscle ache is from. There are many other causes of myalgias too. Statin muscle pain typically occurs in the proximal muscle groups(closer to the trunk of the body) and also lower back. Statin-induced myalgias have occurred up to 3 years after starting a statin.



• Myopathy has been used to refer to all muscle complaints or CK elevations more than 10 times the upper limits of normal with or without associated muscle symptoms. Myositis has been defined as muscle symptoms with increased CK levels. This term implies muscle inflammation but this appears to be a secondary event associated with the healing process.



• Rhabdomyolysis, by strict definition exists whenever there is evidence of muscle damage, such as a mildly elevated CK level but is used clinically to refer to severe muscle damage and is usually associated with kidney dysfunction.

The Muscle Expert Panel of the Statin Safety Task Force believes believes that because of all this confusion about terms, a new format should be made as follows:

• Myopathy should be used as a general term for all muscle problems.



• Symptomatic Myopathy should be used to refer to muscle pain (myalgias), weakness, and cramps.



• Asymptomatic Myopathy should be used to refer to CK (enzyme) elevations without any symptoms.



• Rhabdomyolysis should be used to refer to any evidence of muscle cell destruction with resulting change of kidney function.

What does all this mean?

First of all, muscle problems do occur with all statins. Muscle complaints have been documented to increase with increasing blood levels of the statin. There are 2 different classes of statins: Fat soluble and water soluble. The fat-soluble statins include Lipitor and Zocor and the water-soluble include Pravachol and Crestor.

Since fat-soluble statins can easily enter the inside of the muscle cells, theoretically muscle damage should be increased with their use, as water-soluble statins do not easily get into the muscle cells. This hypothesis has not been confirmed and cases of Rhabdomyolysis, while rare, occurring about 1 time for every 15 million prescriptions written, has occurred with all statins.

My practice is to obtain a baseline CK (enzyme) level before starting statins to see if it is elevated. When a patient on a statin develops myalgia symptoms, I closely monitor them and if severe, I will get a CK level to see if there is any muscle damage.

The problem exists, however, that frequent inquiries about muscle pain may prompt symptoms in suggestible patients. Based on clinical experience, statin-related myalgias resolve when stopping the medicine. There is insufficient evidence to conclude whether myalgia that persists after stopping the statin is caused by the medications. All patients who are symptomatic on statin therapy should have thyroid function tests done as hypothyroidism can exacerbate symptoms.

Also, other medications or nutraceuticals that slow down statin metabolism should be known such as red yeast rice (which may contain a statin and produce myopathy) and grapefruit juice consumption, which impedes the breakdown of fat soluble statins mostly affecting patients on Lipitor.

Regardless of the CK level, if the pain is severe, the statin should be stopped until all the symptoms resolve. Once this occurs, the same statin could be started at the same dose to see if symptoms recur or started at a lower dose. Alternatively, a different statin can be tried.

There is no direct comparison of tolerability among statins and therefore no definitive evidence to recommend a specific statin medication. In other words, there isn't one that's any better than the other, based on established studies. In my practice: however, I will change a patient from a fat-soluble statin to a water-soluble statin if myalgias start and this has been successful for me in reducing muscle problems.

As I said earlier, there is no direct evidence that water-soluble statins produce less muscle problems as compared to fat soluble statins. If the muscle pains are tolerable with or without a CK elevation less than 10 times the upper limit of normal, the Muscle Panel recommends that statin therapy be continued at the same dose or a reduced dose. Generally it is my experience that muscle aches do go away or become tolerable to the patients if the statin is continued. Many physicians are too quick to stop statins with any muscle aches.

The risks versus benefits of statins need to be weighed. One must remember that statins have reduced Cardiovascular Morbidity and Mortality by approximately 40%. While there is no definitive clinical evidence of any strategies that can be used to prevent or reduce muscle injury, there is some evidence that coenzyme Q10 may cause a significant reduction in statin-induced pain. Since the response has been variable, the use of coenzyme Q 10 cannot be recommended with any degree of confidence.

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