Statins May Reduce Your Energy Level

Beatrice A. Golomb, MD, PhD. of the University of California San Diego and colleagues discussed the results of their ongoing studies in the Archives of Internal Medicine online edition regarding cholesterol lowering drugs Simvastatin and Pravastatin and recipients’ perception of their energy level. Their research suggested that Simvastatin might leave its users, especially women, feeling tired and drained after exertion.  The scores hinted that almost 40% of women felt more tired and fatigued during physical activity on Simvastatin than without the lipid-lowering drug.

The trial included 1,016 men and women with low-density lipoprotein (LDL) cholesterol screened at 115- 19- mg/dL who were randomized to receive 20 mg Simvastatin, 40 mg Pravastatin, or placebo each day for 6 months. These patients did not have documented heart disease, cardiovascular disease or diabetes.

There was a worsening of perceived energy level and exertion related fatigue in 4 of 10 women on Simvastatin. The effect was much less, and not significant, with Pravastatin or placebo.   In a recent review of statins and adverse effects in the Cleveland Clinic Journal of Medicine, the authors pointed out that muscles performing work required  fats and lipids as a source of fuel and energy to work successfully. They hypothesized the possibility that the goals of cardiology to reduce lipid levels to prevent cardiovascular disease to extremely low levels may create an environment in working muscles where the lipid levels are too low to generate the fuel or energy needed to perform the exercise and work needed to be done.

Clearly, further research needs to be done.  We must remember all these participants DID NOT have vascular disease and this is a primary prevention study to prevent them from developing cardiovascular disease.  Might there be other methods to achieve this?  Is Simvastatin the only statin to cause this type of problem or will the other statins do the same?  Is this a problem of the particular generic brand of Simvastatin used or is it an across the board effect of Simvastatin?  All these questions require additional research to obtain the answers that we need.

Statins Reduce Risks, Even in the Lowest Risk Groups

Current guidelines for the use of statins in the USA (Lipitor, Zocor, Crestor, Atoravastatin, Simvastatin, Pravastatin, etc.) call for only treating individuals who have a ten-year risk of major vascular event of at least 20%.

European researchers including Borislava Mihaylova, MSc DPhil, and colleagues on the Cholesterol Treatment and Trialists Collaborators team writing in the Lancet question whether the guidelines should be changed to treat individuals with even lower risks. Their large Meta analysis suggests that statins provide substantial benefits for primary prevention – especially in patients with a 5-10% ten year risk of a major vascular event. They looked at data from 27 trials including over 175,000 participants. When they took into account cost and side effects of statins, such as muscle pain and inflammation, rhabdomyolysis, diabetes and hemorrhagic stroke, they concluded that the benefits still far outweighed the risks. They think that the clear-cut affect on lower risk individuals coupled with the fact that almost 50% of vascular events occur in patients without previous cardiovascular disease necessitates the broadening of USA guidelines for treatment of patients. The researchers go on to hypothesize that as more generic statins enter the market, cost concerns will become far less of a factor in the decision to treat or not treat.

They noted that for each 1 mmol/L reduction in LDL cholesterol, there was a 21% reduction in the relative risk of major vascular events, and all cause death, irrespective of age, baseline LDL or previous cardiovascular disease.

This research makes it clear that there is great value in assessing the statistical cardiovascular risk of each individual and being more aggressive in the use of statins than current national guidelines call for.  Incorporating risk tools such as the Framingham Risk assessment plus looking at newer techniques such as the measurement of carotid artery intimal thickness may be appropriate in the decision to choose a statin or not.

Statin Use and Diabetes in Older Women

Older women who take statins may be at an increased risk of developing Type 2 Diabetes Mellitus (adult onset). In a study published in the Archives of Internal Medicine, Dr Ma, of the University of Massachusetts School of Medicine, looked at the 154,000 women in the Women’s Health Initiative who did not have Diabetes when the study began in 1993.  Seven percent (7%) of them were on statins at the time through follow-up, 12 years later.  At that point, 10,242 cases of new cases of diabetes were reported. They theorize that this computes to an almost 50% increase in becoming a Diabetic if you are on a statin as compared to women who are not. Surprisingly, this occurred far more frequently in thin women taking a statin than in heavy or obese women.

The salient points taken out of this research are that women on statins need their liver enzymes monitored frequently they need their blood sugars monitored as well. The overriding message is that as physicians and patients we need to make a monumental effort to control elevated lipids by diet , exercise and weight loss without statins if humanly possible.

This also raises the question of whether we should be measuring HDL and LDL subtypes an Lpa levels on all patients before instituting statin therapy?  While this raises doubt about a popular class of drugs that are a crucial part of the prevention of cardiovascular disease, it does not yet make it clear what the clinical implications are for postmenopausal women on statins.

I will reevaluate all my female patients on statins as I see them for follow-up visits.

Lancet Study Emphasizes Long Term Benefit and Safety of Statin Use

Richard Bulbulia, MD, of the Heart Protection Study Group reported in the Lancet that statin medications are safe and effective over long periods of time.  They looked at 20,536 patients at high risk for vascular events. They studied patients who were between 40 and 80 years old. These patients were randomized to one group receiving Simvastatin (Zocor) daily at the 40 mg dose or placebo for 5.3 years. They were then followed for another six years during which both groups received the statin.

Researchers found that during the initial 5.3 years of the study there was a 23% decrease in major vascular events and an 18% reduction in vascular mortality in the Simvastatin treated group.

They also looked at complications of therapy over the eleven year period and concluded, “Reassuringly, there was no evidence that any adverse effect on particular causes of non–vascular mortality or major morbidity, including site-specific cancer, was emerging during this prolonged follow-up period.”  In an editorial in the same edition, Payal Kohli, MD and Christopher Cannon, MD of the Brigham and Women’s Hospital in Boston said the results “provide contemporary and confirmatory evidence that extended use of statins is safe with respect to possible risk of cancer and non-vascular mortality.”

It is noted that the dosages used are higher than what the FDA currently recommends for Simvastatin due to the risk of muscle injury at higher doses. Despite that, the Lancet editorialists concluded that “concerns should be put to rest and doctors should feel reassured about the long-term safety of this life saving treatment for patients at increased cardiovascular risk.”