Statin Drugs: the New Aspirin?
Due to the failure of previous public health programs to substantially lower cholesterol levels in the general population, medical researchers and health experts are seeking a new approach to better manage the problem. For the last decade, physicians and patients have relied on cholesterol guidelines published by the AHA. According to the AHA, a total cholesterol level of 200 mg/dL or less is considered optimal. Levels of 200-239 mg/dL are considered borderline high risk, and levels above 240 mg/dL are considered high risk.
In May 2001, the National Institutes of Health published new federal guidelines calling for aggressive expansion of the use of statin drugs to treat cholesterol.21 Statin drugs such as atorvastatin (Lipitor®), lovastatin (Mevacor®), pravastatin (Pravachol®), and simvastatin (Zocor®) are among the most potent lipid-lowering agents currently available.
Statins lower cholesterol levels by inhibiting the production of HMG-CoA reductase, resulting in a decrease in cholesterol synthesis in the liver. To compensate for the resulting reduction of cholesterol production, the liver begins to remove LDL circulating in the blood, further reducing overall LDL levels. Statin therapy has been proven to contribute to a decrease in cardiovascular disease morbidity and mortality in recent years, as documented in a number of controlled clinical trials.22 In addition to improvements in lipid profile, statins also appear to confer other benefits, including improved endothelial function, decreased platelet thrombus formation, improved fibrinolytic activity, and reduced frequency of transient myocardial ischemia.23
Although statin therapy was initially used to treat patients suffering from severe hypercholesterolemia, health experts are now pushing to expand statin use to patients with only moderately elevated cholesterol. Moreover, health authorities have called for the use of statins to treat conditions such as diabetes, high blood pressure, high serum triglycerides, and low HDL, as well as for those with a strong family history of heart disease.
Most recently, in July 2004, the journal Circulation published an updated version of the NCEP guidelines, encouraging physicians to aggressively increase the use of statin drugs to lower cholesterol levels. In particular, the report recommends that target LDL levels be reduced from the current 100 mg/dL to 70 mg/dL in patients considered at high risk for a heart attack or death from cardiovascular disease. Additionally, patients at only moderate risk of a heart attack—those with heart disease, diabetes, or other risk factors—are now being encouraged to reduce their cholesterol levels by 30-40%.24
Not surprisingly, the new guidelines could dramatically increase the number of patients on statin drugs to as many as 50 million.25 In an embarrassing oversight, the same government panel drafting the new guidelines failed to mention in its report that most of its panelists are linked to pharmaceutical companies that manufacture statin drugs. Six of the nine panelists had either received grants from or were paid consulting or speakers’ fees by the companies that make some of the most popular statins, including Pfizer’s Lipitor®, Bristol-Myers Squibb’s Pravachol®, Merck’s Mevacor®, and AstraZeneca’s Crestor®.26
Statins and Side Effects
While statin drugs effectively lower LDL, they also produce serious side effects. In 1990, Folkers theorized that inhibition of HMG-CoA reductase would also inhibit intrinsic biosynthesis of coenzyme Q10 (CoQ10), a central compound in the mitochondrial respiratory chain. Dr. Folkers’ researchers stated, “If lovastatin were to reduce levels of CoQ10, this reduction would constitute a new risk of cardiac disease, since it is established that CoQ10 is indispensable for cardiac function.”
When the researchers examined five hospitalized patients aged 43 to 72, they found that lovastatin did in fact cause CoQ10 levels to drop. Furthermore, the patients showed evidence of increased cardiac distress, a potentially life-threatening situation for patients hospitalized with class IV cardiomyopathy. The researchers concluded, “Although a successful drug, lovastatin does have side effects, particularly including liver dysfunction, which presumably can be caused by the lovastatin-induced deficiency of CoQ10.”27 Taking supplemental CoQ10 may potentially offset this side effect, but other, more serious side effects cannot be so easily resolved.
For example, rhabdomyolysis is a rare but potentially deadly condition that occurs when large numbers of skeletal muscle cells die. As the rapidly dying cells deteriorate, they release large quantities of muscle proteins into the bloodstream, quickly overwhelming the kidneys. An analysis of the Food and Drug Administration’s side-effect registry, conducted in 2001 by the consumer watchdog group Public Citizen, discovered that statin drugs were linked to 72 fatal and 772 non-fatal cases of rhabdomyolysis between October 1997 and December 2000. In August 2001, pharmaceutical giant Bayer AG was forced to remove its statin drug Baycol® (cerivastatin) from the market after it was found to be responsible for killing at least 31 people.28
More recently, an article in the June 26, 2004, issue of The Lancet raised concerns about the FDA’s approval of one of the newest statin drugs, Crestor®, citing pre-approval evidence that the drug caused rhabdomyolysis. According to the author, Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group, Crestor® was approved despite an FDA claim that new cholesterol drugs would be approved only if they presented a comparable or lower risk of rhabdomyolysis than drugs already on the market.
According to Wolfe, patients taking Crestor® experienced severe muscle deterioration at higher rates than patients taking other cholesterol-lowering drugs. In fact, the incidence of post-marketing reports of rhabdomyolysis for Crestor® appears to exceed that of all other currently marketed statins. From its approval in August 2003 to mid-April 2004,18 patients using Crestor®, including 11 in the US, suffered severe muscle deterioration. In addition, eight cases of acute kidney failure and four cases of kidney insufficiency related to the use of Crestor® have been reported.29
Unknown Long-Term Effects
While the cardioprotective benefits of statin drugs outweigh the known side effects, the most recent NCEP recommendations may result in tens of millions of new patients taking statins for a period of decades, and possibly for a lifetime. Unfortunately, data on the long-term use of statins are scant. In one paper published in the Journal of the American Medical Association in 1996, researchers set off a furious round of debate by raising the possibility of long-term statin use causing cancer. In the original paper, authors Newman and Hulley pointed out that all statin drugs have been shown to induce cancer in experimental lab rodents, and in some cases, the amount of statins causing cancer in the animals matched dosages being prescribed to humans. While conceding that extrapolating the incidence of cancer in rodents to humans is “an uncertain process,” the authors wrote that “lipid-lowering drug treatment, especially with the fibrates and statins, should be avoided except in patients at high short-term risk of coronary heart disease.”30 Interestingly, more recent studies indicate that statin drugs might actually reduce the incidence of certain cancers.31-37
Another potentially serious long-term problem appeared in a case study initiated after several reports and a single epidemiological study suggested that statins cause damage to the peripheral nervous system. After reviewing patient records from 1994 to 1998, the authors verified diagnosis of idiopathic polyneuropathy in 166 patients receiving statin therapy for at least two years, concluding in their 2002 paper that “long-term exposure to statins may substantially increase the risk of polyneuropathy.”38
Healthy Options for Lowering Cholesterol
In their enthusiasm to reduce premature deaths from heart attack and strokes, the authors of the new cholesterol guidelines are recommending that millions of Americans start taking statin drugs. This recommendation ignores the danger of potential side effects from the long-term use of statins. Would informed health consumers willingly choose to lower their risk of cardiovascular disease if it meant substantially increasing their chances of developing health problems after a decade or two?
In a recent opinion piece published in the Washington Post, Dean Ornish, MD, clinical professor of medicine at the University of California, San Francisco, and president of the nonprofit Preventive Medicine Research Institute, wrote, “As tens of millions of people begin taking these medications for decades, more long-term side effects are likely to become apparent.” Dr. Ornish also questioned why the panel failed to recommend other options, such as diet and lifestyle changes, that for most people “can be a safe and effective alternative to a lifetime of cholesterol-lowering drugs.”39
One of the newest and most effective alternatives to statin drugs is a patented, proprietary formula comprising citrus and palm fruit extracts that contain polymethoxylated flavones and tocotrienols. It has been shown in human trials to significantly reduce total cholesterol, LDL, and triglycerides. Additionally, the powerful antioxidant and anti-inflammatory properties of the extracts in this natural formulation (trademarked under the name SytrinolTM) are known to contribute to managing additional cardiovascular disease risk factors.