Statins: The new wonder drugs
Statins might just prove to be real miracle drugs. They do a great job at lowering cholesterol, and they also appear to have a multitude of other medical benefits. They work by altering the metabolism of cholesterol, a complex fat that the body needs for many purposes. For example, cholesterol forms a vital component of cell membranes and nerve sheaths; it forms the basis of sex hormones; and it enables bile acids to process the food we eat. Most of the body’s cholesterol is produced by liver cells, and most of the rest comes from the food we eat.
Cholesterol is insoluble in water, so it can’t circulate in blood plasma without a protective shroud of lipoproteins, which are part fat and part protein. Cholesterol’s ultimate destination depends on whether the shroud consists of low-density lipoprotein (LDL) or high-density lipoprotein (HDL). LDL particles deliver cholesterol to cells throughout the body; HDL particles mop up excess cholesterol and carry it back to the liver for disposal. If the body produces more LDL cholesterol than the cells can absorb, it settles in artery walls and contributes to atherosclerotic plaque. That’s why LDL is often called “bad” cholesterol and HDL “good” cholesterol — even though the body needs both kinds.
As researchers came to suspect that high LDL levels raised the risk for heart attack and stroke, they began to explore drug treatments. By the 1980s, three classes of drugs were available: fibrates, which reduce the liver’s production of triglycerides (non-cholesterol fat that’s also carried by lipoproteins); bile acid sequestrants, which reduce cholesterol by binding with bile acids; and niacin, which raises HDL levels and lowers triglycerides. All these agents have unpleasant side effects: Fibrates cause nausea and upset stomach; bile acid sequestrants cause flatulence and constipation; and niacin triggers flushing.
Statins And Cholesterol
Lovastatin, the first of the statin drugs, was introduced in 1987. These drugs work by blocking the liver enzyme HMG-CoA reductase, which promotes cholesterol production (see diagram). The statins can dramatically reduce circulatory cholesterol with relatively negligible side effects. Their use continues to grow as guidelines for cholesterol are revised downward and clinical study shows that these drugs are effective in preventing heart attacks. They also appear to have a multitude of other benefits, which are being discovered on a near-monthly basis. Researchers postulate that these pleiotropic (multiple) effects may be due to the drug’s inflammation-lowering, rather than cholesterol-lowering properties. Six different statins are currently available by prescription: atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Lovastatin), pravastatin (Lipostat), rosovastatin (Crestor), and simvastatin (Zocor). Although chemically they are nearly identical, small differences in their molecular structure are in some cases responsible for properties specific to one or two statins. In addition to lowering the risk of heart attacks and strokes by reducing cholesterol, these wonder drugs can do many other things:
• Statins may prevent stroke. In a recent clinical study of 3,500 adults who had experienced atrial fibrillation or were at high risk for that form of arrhythmia, statins lowered the risk by 61 percent. The finding, reported in the Journal of the American College of Cardiology of Feb. 26, 2008, is significant because about five percent of people have atrial fibrillation, which puts patients at risk for a blood-clot-induced (hemorrhagic) stroke. About one and a half years ago, a meta-analysis of 42 clinical trials that included more than 121,000 patients found that statin therapy reduced the risk of a fatal or nonfatal non-hemorrhagic stroke caused by plaque buildup in the carotid arteries but not hemorrhagic stroke.
• Statins reduce deaths from respiratory diseases. A review of more than 8,600 US veterans, mostly men over age 65, hospitalized with community-acquired pneumonia (CAP), found that those who were taking statins at the time of hospital admission were only half as likely to die as those who were not taking statins. The study, published in the February 2008 European Respiratory Journal (ERJ), follows on the heels of other studies in the ERJ and Chest, which found that statins reduce deaths from chronic bronchitis, emphysema, and influenza. Moreover, a study reported in the Oct. 15, 2007 issue of the American Journal of Respiratory and Critical Care Medicine found that statins can dramatically slow the decline in lung function related to aging. The effect was consistent whether patients had never smoked, quit years ago, quit recently, or were active smokers.
• Statins ameliorate heart failure. A large database review study published on Jan. 15, 2008 in the American Journal of Cardiology found that statins lower the one- and three-year mortality rates of patients with right-sided heart failure, irrespective of the patient’s age, total cholesterol level, or presence of coronary artery disease, diabetes or hypertension. This supports the findings of a study presented at the 2007 American Heart Association meeting, in which patients who took rosuvastatin for 12 months had improved ejection fractions and greater heart function efficiency. The effect is likely due to the activation of circulating stem cells. As a result, patients experienced growth of new blood vessels in the large muscles and regeneration of endothelial cells lining the blood vessels.
• Statins help protect against heart attack. A Japanese study published in the March 30, 2007 issue of The Lancet found that statins plus fish oil supplements provided substantial protection against heart attack. Patients were observed for four to six years, after which researchers noted that patients with documented heart disease who took statin and fish oil combination had 19-percent fewer major coronary events and fewer incidence of unstable angina.
• Statins may reverse coronary artery disease. In 2006, a large multinational study was the first to show that statin therapy may actually cause fatty plaques inside the arteries to shrink. In this study, patients with coronary artery disease took the maximum dose of rosuvastatin and were monitored with intravascular ultrasound. Results showed that atherosclerosis regressed in 78 percent of patients (April 5, 2006, Journal of the American Medical Association). Whether the same effect occurs with other statins is yet unknown.
• Statins may prevent Alzheimer’s. Researchers, conducting a small study reported in the August 2007 issue of Neurology, found fewer tangles and plaques characteristic of Alzheimer’s disease in the brain of deceased elderly men and women who had taken statins, compared with those who had not. While more extensive study is needed, the possibility that statins might prevent this devastating illness, for which no prevention or cure is known, is exciting indeed.
And Now Comes Jupiter
Another exciting news on statins was announced in the 2008 American Heart Association meeting in New Orleans last November. A large new study suggested that millions more people could benefit from statins, even if they have low cholesterol, because the drug can significantly lower their risk of heart attacks, strokes, and death. The study, called the “Justification for the Use of Statins in Primary Prevention,” or JUPITER, which involved nearly 18,000 people worldwide, tested statin treatment in men 50 and older and in women 60 and older who did not have high cholesterol or histories of heart disease. What they did have was high levels of C-reactive protein or CRP, which indicates inflammation in the body. It found that the risk of heart attack was more than cut in half for people who took statins.
Those people were also almost 50-percent less likely to suffer from stroke or need angioplasty or bypass surgery, and they were 20-percent less likely to die during the study. The statin was considered so beneficial that an independent safety monitoring board stopped what was supposed to be a five-year trial last March after only less than two years. Scientists said the research could provide clues on how to address a long-confounding statistic: that half of heart attacks and strokes occur in people without high cholesterol. “These are findings that are really going to impact the practice of cardiology,” said Dr. Elizabeth G. Nabel, director of the US National Heart, Lung, and Blood Institute. “It’s at a minimum an extremely important study and has the potential to be a landmark study.” Some experts stress, however, that more research is needed to further pinpoint the patients with normal to low cholesterol who will benefit from statin therapy.
Are Statins Right For You?
Doctors universally agree that the benefits of statins far outweigh the risks. Their side effects are widely known, and for the most part, mild. They include muscle pain (myalgia) and elevation of liver enzymes, which must be checked regularly. Rarely, they can cause rhabdomyolysis — severe muscle deterioration, with the release of muscle proteins in the blood. If that happens, the kidneys may fail. If you have a family or personal history of coronary artery disease, atrial fibrillation, or stroke, talk to your doctor about statins. High doses that increase the risk of side effects may not be necessary. For most people, moderate, more tolerable doses of these wonder drugs may be sufficient in providing you with significant, beneficial health benefits.
AN APPLE A DAY
By Tyrone M. Reyes, M.D.
Updated February 24, 2009 12:00 AM