The fact that there is no statistically proven cardiovascular benefit from the use of statins for cholesterol reduction in women was first publicly disclosed by Uffe Ravnskov in his book, The Cholesterol Myths and has been corroborated repeatedly by numerous longitudinal clinical studies.
The ASCOT study, the largest randomized clinical study of statin effectiveness in women, found that the women who took Lipitor, developed more heart attacks than women in the group given placebo.
While not statistically significant this finding hardly supports cardiovascular benefit. In this ASCOT study, 2,000 women were included among 10,000 patients having elevated blood pressure and at least three other cardiovascular risk factors.
Again and again, clinical studies have failed to show that the use of statins lowers cardiovascular risk in women who do not already have coronary heart disease or diabetes.Despite this, women have been a major target group for the promotion of statins. The effect of such advertising is to provide women with the impression that statins protect against cardiovascular disease.
Throughout this period the FDA has stressed that the relationship between statins' cholesterol lowering effect and its effect on cardiovascular disease is not known. For women without heart disease or stroke there are no clinical trials showing that cholesterol lowering reduces women's risk of developing heart disease, heart attack, stroke, cardiovascular disease death, illness overall or even death from any cause. Again and again, clinical trials examining the prevention of acute coronary events by the use of statins have found no statistically significant benefit.
Research results in the past several years cast increasing doubt as to cholesterol's role in atherosclerosis, now pointing more and more convincingly to inflammation as the principle factor. Statin drugs appear to reduce cardiovascular risk not by cholesterol manipulation but by inflammation suppression and are now recognized for the powerful anti-inflammatory agents they really are.
The mechanism of action for this completely unexpected effect is suspected to be via the inhibition of nuclear factor kappa B, a transcription factor vital to our immunodefense system. In light of this new information it is not surprising that the use of any statin in the targeted group of women having neither cardiovascular disease nor diabetes and therefore insignificant vascular inflammation, would have little or no provable benefit.Clearly we are seeing statins as useful more for secondary than for primary prevention. In the presence of high cardiovascular risk such as a patient with history of heart attack or stroke documenting underlying atherosclerosis and inflammation, anti-inflammatory agents such as statins have obvious value.
Pfizer's promotion of Lipitor has thus created an artificial demand for Lipitor, which would not exist if full and fair disclosure had been made concerning benefit lack in the females free of diagnosed heart disease or diabetes.
The side effect profile of statin drugs is of major concern. The statin associated rhabdomyolysis deaths alone, the majority of which have been women, should give all physicians reason to ask themselves, "Is the expanding use of statins in primary prevention really justified?"
Harriet Rosenberg and Danielle Allard in a comprehensive review published in Scandinavian Cardiovascular Journal, 1-6, 2008, summarized that in the reports of statin use in women they have found a consistent pattern of "overestimation of benefit and under estimation of harm." They found insufficient evidence in any study to determine whether lowering lipid levels by any method reduced the risk of heart attack or stroke because women were under-represented in trials. The consensus of literature search found that high cholesterol in women was not a predictor of cardiovascular events or stroke after age 50.
Their detailed meta-analysis of data for women found that, for high-risk primary prevention, the evidence underpinning the US guidelines did not substantiate the 2004 pronouncement. They concluded that for women with known cardiovascular disease, treatment of hyperlipidemia is effective in reducing CHD events and CHD mortality, but that it does not affect total mortality. On the subject of cancer, they emphasized the importance of the PROSPER study (ages over 70) report of a 25% statistically significant increase of new cancers overall, including more first breast cancer diagnoses in the treatment (n=18) than in the placebo group.
They describe statin-impaired patients who presented with conditions that undermine activities of daily life, primary among which is muscle pain, nullifying CV risk reduction by exercise. They found that recent research supports the perspective that statins interfere with exercise, indicating a population of as many as 25% of users who experience ‘‘muscle fatigue, weakness, aches, and cramping due to statin therapy and potentially dismissed by patient and physician.'' They stressed the work of Edison and Muenke, assessing 22 cases of babies born with birth defects whose mothers had been taking statins in their first trimester.
All in all their study corroborates existing findings of under-reporting of statin side effects and overstating the benefits of statins. The medical community in general seems currently unaware of these flaws.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor