By Sally Fallon and Mary G. Enig, PhD
Originally printed at Weston A. Price

PROVE-IT (2004)

PROVE-IT (PRavastatin Or AtorVastatin Evaluation and Infection Study),⁵⁰ led by researchers at Harvard University Medical School, attracted immense media attention. "Study of Two Cholesterol Drugs Finds One Halts Heart Disease," was the headline in the New York Times.⁵¹ In an editorial titled "Extra-Low Cholesterol," the paper predicted that:

"The findings could certainly presage a significant change in the way heart disease patients are treated. It should also start a careful evaluation of whether normally healthy people could benefit from a sharp drug-induced reduction in their cholesterol levels."⁵²

The Washington Post was even more effusive, with a headline "Striking Benefits Found in Ultra-Low Cholesterol."⁵³

"Heart patients who achieved ultra-low cholesterol levels in one study were 16 percent less likely to get sicker or to die than those who hit what are usually considered optimal levels. The findings should prompt doctors to give much higher doses of drugs known as statins to hundreds of thousands of patients who already have severe heart problems, experts said. In addition, it will probably encourage physicians to start giving the medications to millions of healthy people who are not yet on them, and to boost dosages for some of those already taking them to lower their cholesterol even more," they said.

The study compared two statin drugs, Lipitor and Pravachol. Although Bristol Myers-Squibb (BMS), makers of Pravachol, sponsored the study, Lipitor (made by Pfizer) outperformed its rival Pravachol in lowering LDL. The "striking benefit" was a 22 percent rate of death or further adverse coronary events in the Lipitor patients compared to 26 percent in the Pravachol patients.

PROVE-IT investigators took 4,162 patients who had been in the hospital following an MI or unstable angina. Half got Pravachol and half got Lipitor. Those taking Lipitor had the greatest reduction of LDL-cholesterol -- LDL in the Pravachol group was 95, in the Lipitor group it was 62 -- a 32 percent greater reduction in LDL levels and a 16 percent reduction in all-cause mortality. But that 16 percent was a reduction in relative risk.

As pointed out by Red Flags Daily columnist Dr. Malcolm Kendrick, the absolute reduction in the rate of the death rate of those taking Lipitor rather than Pravachol, was one percent, a decrease from 3.2 percent to 2.2 percent over two years.⁵⁴ Or, to put it another way, a 0.5 percent absolute risk reduction per year--these were the figures that launched the massive campaign for cholesterol-lowering in people with no risk factors for heart disease, not even high cholesterol.

And the study was seriously flawed with what Kendrick calls "the two-variables conundrum."

"It is true that those with the greatest LDL lowering were protected against death. However, ... those who were protected not only had a greater degree of LDL lowering, they were also on a different drug which is rather important, yet seems to have been swept aside on a wave of hype. If you really want to prove that the more you lower the LDL level, the greater the protection, then you must use the same drug. This achieves the absolutely critical requirement of any scientific experiment, which is to remove all possible uncontrolled variables ... As this study presently stands, because they used different drugs, anyone can make the case that the benefits seen in the patients on atorvastatin [Lipitor] had nothing to do with greater LDL lowering; they were purely due to the direct drug effects of atorvastatin."

Kendrick notes that the carefully constructed J-LIT study, published two years earlier, found no correlation whatsoever between the amount of LDL lowering and death rate. This study had 10 times as many patients, lasted almost three times as long and used the same drug at the same dose in all patients. Not surprisingly, J-LIT attracted virtually no media attention.

PROVE-IT did not look at side effects but Dr. Andrew G. Bodnar, senior vice president for strategy and medical and external affairs at Bristol Meyer Squibb, makers of the losing statin, indicated that liver enzymes were elevated in 3.3 percent of the Lipitor group but only in 1.1 percent of the Pravachol group, noting that when liver enzyme levels rise, patients must be advised to stop taking the drug or reduce the dose.⁵⁵ And withdrawal rates were very high: 33 percent of patients discontinued Pravachol and 30 percent discontinued Lipitor after two years due to adverse events or other reasons.⁵⁶

REVERSAL (2004)

In a similar study, carried out at the Cleveland Clinic, patients were given either Lipitor or Pravachol. Those receiving Lipitor achieved much lower LDL-cholesterol levels and a reversal in "the progression of coronary plaque aggregation."⁵⁷ Those who took Lipitor had plaque reduced by 0.4 percent over 18 months, based on intravascular ultrasound (not the more accurate tool of electron beam tomography); Dr. Eric Topol of the Cleveland Clinic claimed these decidedly unspectacular results:

"Herald a shake-up in the field of cardiovascular prevention ... the implications of this turning point--that is, of the new era of intensive statin therapy--are profound. Even today, only a fraction of the patients who should be treated with a statin are actually receiving such therapy ... More than 200 million people worldwide meet the criteria for treatment, but fewer than 25 million take statins."⁵⁸

Not surprisingly, an article in The Wall Street Journal noted "Lipitor Prescriptions Surge in Wake of Big Study."⁵⁹

But as Dr. Ravnskov points out, the investigators looked at change in atheroma volume, not the change in lumen area, "a more important parameter because it determines the amount of blood that can be delivered to the myocardium. Change of atheroma volume cannot be translated to clinical events because adaptive mechansims try to maintain a normal lumen area during early atherogenesis."⁶⁰

Other Uses

With such paltry evidence of benefit, statin drugs hardly merit the hyperbole heaped upon them. Yet the industry maintains a full court press, urging their use for greater and greater numbers of people, not only for cholesterol lowering but also as treatment for other diseases like:

• Cancer
• Multiple sclerosis
• Osteoporosis
• Stroke
• Macular degeneration
• Arthritis
• Even mental disorders such as memory and learning problems, Alzheimers and dementia.⁶¹

New guidelines published by the American College of Physicians call for statin use by all people with diabetes older than 55 and for younger diabetes patients who have any other risk factor for heart disease, such as high blood pressure or a history of smoking.⁶² David A. Drachman, professor of neurology at the University of Massachusetts Medical School calls statins "Viagra for the brain."⁶³ Other medical writers have heralded the polypill, composed of a statin drug mixed with a blood pressure medication, aspirin and niacin, as a prevent-all that everyone can take. The industry is also seeking the right to sell statins over the counter.

Can honest assessment find any possible use for these dangerous drugs? Dr. Peter Langsjoen of Tyler, Texas, suggests that statin drugs are appropriate only as a treatment for cases of advanced Cholesterol Neurosis, created by the industry's anti-cholesterol propaganda. If you are concerned about your cholesterol, a statin drug will relieve you of your worries.

Creative Advertising

The best advertising for statin drugs is free front-page coverage following gushy press releases. But not everyone reads the paper or goes in for regular medical exams, so statin manufacturers pay big money for creative ways to create new users.

For example, a new health awareness group called the Boomer Coalition supported ABC's Academy Awards telecast in March of 2004 with a 30-second spot flashing nostalgic images of celebrities lost to cardiovascular disease--actor James Coburn, baseball star Don Drysdale and comedian Redd Foxx. While the Boomer Coalition sounds like a grass roots group of health activists, it is actually a creation of Pfizer, manufacturers of Lipitor. "We're always looking for creative ways to break through what we've found to be a lack of awareness and action," says Michal Fishman, a Pfizer spokeswoman. "We're always looking for what people really think and what's going to make people take action," adding that there is a stigma about seeking treatment and many people "wrongly assume that if they are physically fit, they aren't at risk for heart disease."⁶⁴ The Boomer Coalition Web site allows visitors to "sign up and take responsibility for your heart health," by providing a user name, age, e-mail address and blood pressure and cholesterol level.

A television ad in Canada admonished viewers to "Ask your doctor about the Heart Protection Study from Oxford University." The ad did not urge viewers to ask their doctors about EXCEL, ALLHAT, ASCOT, MIRACL or PROSPER, studies that showed no benefit--and the potential for great harm--from taking statin drugs.

The Costs

Statin drugs are very expensive--a course of statins for a year costs between $900 and $1,400. They constitute the mostly widely sold pharmaceutical drug, accounting for 6.5 percent of market share and $12.5 billion in revenue for the industry. Your insurance company may pay most of that cost, but consumers always ultimately pay with higher insurance premiums. Payment for statin drugs poses a huge burden for Medicare, so much so that funds may not be available for truly lifesaving medical measures.

In the UK, according to the National Health Service, doctors wrote 31 million prescriptions for statins in 2003, up from 1 million in 1995 at a cost of 7 billion pounds--and that's just in one tiny island.⁶⁵ In the United States, statins currently bring in $12.5 billion annually for the pharmaceutical industry. Sales of Lipitor, the number-one-selling statin, are projected to hit $10 billion in 2005.

Even if statin drugs do provide some benefit, the cost is very high. In the WOSCOP clinical trial where healthy people with high cholesterol were treated with statins, the five-year death rate for treated subjects was reduced by a mere 0.6 percent. As Dr. Ravnskov points out,⁶⁶ to achieve that slight reduction about 165 healthy people had to be treated for five years to extend one life by five years. The cost for that one life comes to $1.2 million dollars. In the most optimistic calculations, the costs to save one year of life in patients with CHD is estimated at $10,000, and much more for healthy individuals. "This may not sound unreasonable," says Dr. Ravnskov. "Isn't a human life worth $10,000 or more?"

"The implication of such reasoning is that to add as many years as possible, more than half of mankind should take statin drugs every day from an early age to the end of life. It is easy to calculate that the costs for such treatment would consume most of any government's health budget. And if money is spent to give statin treatment to all healthy people, what will remain for the care of those who really need it? Shouldn't health care be given primarily to the sick and the crippled?"

References

Related Articles:

The Truth About Cholesterol-Lowering Drugs (Statins), Cholesterol, and Health

Crestor and Other Statins: Are They Really Worth the Risk?

Half of Population Will be Taking Statins

Statins - Is the Danger is the Dose?