If cholesterol lowering itself isn't a panacea, why is it that statins do work for people with existing heart disease? In his laboratory at the Vascular Medicine unit of Brigham & Women's Hospital in Cambridge, Mass., Dr. James K. Liao began pondering this question more than a decade ago. The answer, he suspected, was that statins have other biological effects.
Since then, Liao and his team have proved this theory. First, a bit of biochemistry. Statin drugs work by bollixing up the production of a substance that gets turned into cholesterol in the liver, thus reducing levels in the blood. But the same substance turns out to be a building block for other key chemicals as well. Think of a toy factory in which the same plastic is fashioned into toy cars, trucks, and trains. Reducing production of the plastic cuts not only the output of toy cars (cholesterol) but also trucks and trains. In the body, these additional products are signaling molecules that tell genes to turn on or off, causing both side effects and benefits.
Liao has charted some of these biochemical pathways. His recent work shows that one of the trucks, as it were—a molecule called Rho-kinase—is key. By reducing the amount of this enzyme, statins dial back damaging inflammation in arteries. When Liao knocks down the level of Rho-kinase in rats, they don't get heart disease. "Cholesterol lowering is not the reason for the benefit of statins," he concludes.
The work also offers a possible explanation of why that benefit is mainly seen in people with existing heart disease and not in those who only have elevated cholesterol. Being relatively healthy, their Rho-kinase levels are normal, so there is little inflammation. But when people smoke or get high blood pressure, their Rho-kinase levels rise. Statins would return those levels closer to normal, counteracting the bad stuff.
Add it all together, and "current evidence supports ignoring LDL cholesterol altogether," says the University of Michigan's Hayward. In a country where cholesterol lowering is usually seen as a matter of life and death, these are fighting words. A prominent heart disease physician and statin booster fumed at a recent meeting that "Hayward should be held accountable in a court of law for doing things to kill people," Hayward recounts. NECP's Cleeman adds that, in his view, the evidence against Hayward is overwhelming.
But while the new analyses may rile those who have built careers around the need to reduce LDL, they also point the way to using statins more effectively. Surprisingly, both sides in the debate agree on the general approach. For anyone worried about heart disease, the first step should always be a better diet and increased physical activity. Do that, and "we would cut the number of people at risk so dramatically" that far fewer drugs would be needed, says Krauss. For those people who still might benefit from treatment, a recent analysis by Hayward shows that statins might better be prescribed based on patients' risk of heart disease, not on their LDL cholesterol levels. The higher the risk, the better the drugs seem to work. "If two patients have the same risk, the evidence says they get the same benefit from statins, whatever their LDL levels," Hayward says.
Ways to fine-tune this approach may be coming soon. The company that first sequenced the human genome, Celera Group (CRA), has found a genetic variation that predicts who benefits from the drugs. Perhaps 60% of the population has it, says Dr. John Sninsky, vice-president of discovery research, and for everyone else, the NNT is sky-high. "It does not relate at all to your cholesterol level," Sninsky adds.
If the drugs were used more rationally, drugmakers would take a hit. But the nation's health and pocketbook might be better off. Could it happen? Will data on NNTs, the weak link to cholesterol, and knowledge of genetic variations change what doctors do and what patients believe? Not until the country changes the incentives in health care, says UCLA's Hoffman. "The way our health-care system runs, it is not based on data, it is based on what makes money."
...current evidence supports ignoring LDL cholesterol altogether," says the University of Michigan's Hayward.
Now, that's going to be an interesting argument.
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- Jim
�Look! Out the window! There is a flying cow!� St.Thomas Aquinas looked, and they all burst into laughter. He calmly replied, �I would rather believe that the cow is flying than that my friends would lie to me!�
So to spare one person a heart attack, 100 people had to take Lipitor for more than three years. The other 99 got no measurable benefit. Or to put it in terms of a little-known but useful statistic, the number needed to treat (or NNT) for one person to benefit is 100.
It is disgusting no matter how it is analyzed.
You know? The best cure for high prices is high prices. It happened in the oil market. Now that market is suffering from over correction in price. People are loosing jobs. Countries are suffering, if their only resource was oil.
It happened in the corn market with high prices. Now the price of ethanol is much too high compared to oil. So, corn looses. And corn farmers too.
The same thing will happen in the pharmaceutical industry. Patients will tell doctors that they must have alternatives; because they lost their jobs and have no insurance. People will stop going to doctors for every little thing.
These statins are lifelong meds. People should realize this and save their money for alternatives.
I agree, JFH. I think money will become a driving force (or probably already is, after looking at my husband's hospital bills).
with more people not having insurance, and the internet so available, more and more people are going to be trying "alternative" methods when someone in their family gets sick. It won't be because they are disillusioned with traditional medicine... it will be because they can no longer afford it.
business week cover story on statins
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