Although many health care professionals have come forward in recent years with warnings that prescription drugs are one of the largest killers in the field of medicine, the general public apparently remains unaware of the yearly death toll attributed to legal drug use - judging by the on-going over-prescribing of prescription drugs.
And nowhere is this fact more obvious than in the case of Lipitor. By use of the manufactured fear of high cholesterol, Pfizer has been able to transform tens of millions of people into life-long customers for Lipitor.
Without question, Lipitor is the all-time granddaddy of blockbuster drugs. It was the first drug to reach $10 billion in sales worldwide, and it has earned close to $50 billion in revenue for Pfizer since 2000.
According to Pfizer's first quarter SEC filing for 2006, Lipitor "is the most widely used treatment for lowering cholesterol and the best-selling pharmaceutical product of any kind in the world, reaching over $3.1 billion in worldwide sales in the first quarter of 2006, an increase of 1% compared to the same period in 2005."
"In the U.S.," the filing reports, "sales of $2 billion represent growth of 3% over the previous year's first quarter."
In fact, according to an estimate in Bloomberg News on August 24, 2006, by Deutsch Bank analyst, Barbara Ryan, Lipitor generated about 40% of Pfizer's 2005 profits.
Lipitor recently bagged a special honor for Pfizer when the Prescription Access Litigation Project (PAL), announced the winners of the 2006 Bitter Pill Awards on April 26, 2006 and the drug shared an award with Crestor, its archrival anti-cholesterol drug.
The Awards honor drug makers "engaging in over-zealous and questionable marketing practices," to highlight the problems caused by the heavy marketing of prescription drugs, and specifically Direct-to-Consumer Advertising (DTCA), to include television, radio, magazine and internet ads that target consumers directly, rather than doctors.
According to PAL, statin drugs vary in price from about $33 a month for generics to $162 for brand-names, but millions of people for whom a generic would be fine are taking Lipitor and Crestor, due to their aggressive marketing campaigns.
Overall, the pharmaceutical industry spent $4.65 billion in 2005 for DTC advertising of brand-name drugs, a 4.7% increase over 2004. But experts say its money well-spent because every dollar invested brings back between $1.50 to $4.20 in additional sales, according to PAL.
In 2005, Pfizer spent a total of $93,435,000 on DTC for Lipitor and as a result, the drug's price increased by more than 50% of the rate of inflation.
Another contributing factor to the rise in Lipitor's price might well be due to the salaries of Pfizer's top executives. For instance, as CEO, recently retired Henry McKinnell's annual compensation package in 2005 included: $2, 270,500 (salary) + 3,700,000 (bonus) + 14,499,795 (stock options) + 5,489,400 (LTIP Payouts) + 427,370 (other) = $26,387,065.
However, analysts say the top brass in the company executives are looking for ways to calm investors who are infuriated over the $83 million retirement package Mr McKinnell recently walked off with, after watching a 40% slide in Pfizer stock price during the CEO's 5-year reign. The blue-chip stock, which reached its peak of $50 in 1999 is now trading in the range of $20.27, according to Trading Markets on August 20, 2006.
In announcing the Lipitor-Crestor Bitter Pill award, PAL stated, "The enormous potential market for these drugs, which patients take (and pay for) for years, has caused our award winners to significantly overpromote their drugs."
"The marketing campaigns," PAL said, "have created the impression that anyone and everyone with even slightly high cholesterol needs them."
"This marketing gives short shrift to the much cheaper but effective generic statins," the report notes, "as well as to lifestyle changes, such as better diet and more exercise, that should be the first line of treatment for millions of people who have high cholesterol but no other major risk factors."
DTC is used as a promotional tool to expand the market for drugs far beyond their intended purpose. Lipitor is FDA approved for people who already have heart disease or are at great risk of developing heart disease. But as a result of Pfizer's massive marketing campaign, millions of people with only elevated cholesterol levels are taking the drug every day.
But yet, experts say, despite the drastic increase in statin use, the death rate from heart disease has not changed over the last 75 years. If low cholesterol prevents heart disease, they say, by now studies should show a correlation between lower cholesterol and less heart disease, but they don't.
In reality, experts say, the only thing Lipitor does is lower cholesterol. According to Dr John Abramson, MD, clinical instructor of ambulatory care at Harvard Medical School and author of Overdosed America, "The idea that lowering cholesterol always reduces the risk of heart disease has become the conventional wisdom, which drug companies like Pfizer have taken great pains to promote."
"But for women under 65 and people over 65 with no history of heart disease or diabetes," he told Consumer Affairs, "the evidence just isn't there."
"Millions of women and seniors," he said, "are spending huge sums to take Lipitor every day despite a lack of proof that it's doing anything beneficial for them, and may actually be harming the elderly."
A recent study in the August 10, 2006, New England Journal of Medicine, funded by Pfizer, appears to back up these assertions, at least when it comes to stokes.
The study found Lipitor to be not much better, if any, than a placebo at preventing stokes. And in fact, the study showed the drug to be far less effective in preventing the worst kind of strokes than a placebo.
The study involved more than 4,700 people who had recently had a stroke or "mini-stroke." The subjects had no known coronary heart disease, and their level of "bad" cholesterol was higher than optimal.
They were assigned to take either Lipitor or a placebo daily. After an average of nearly five years, 265 of those in the Lipitor group had had another stroke, compared with 311 in the placebo group, or a difference of 16%, but the study found that mortality rate was about the same in both groups.
However, the study showed that the most serious type of stroke, the hemorrhagic stroke, was by far more common in the Lipitor group with 55 cases, verses only 33 cases in the placebo group.
That said, a key factor not highlighted by the authors of the study, is that hemorrhagic stroke is associated with a higher death rate than ischemic stroke, according to the National Heart Foundation.
But then a caveat at the end of the article explains why the interpretation of the study is manipulated with words that favor Lipitor where it says the study was funded by Pfizer, the maker of Lipitor, which also has financial ties to the study's authors.
Pfizer received another surprise of sorts in September last year when Health Care For All, a PAL coalition member, and others, filed a nationwide class action lawsuit in US District Court for the District of Massachusetts against the company on behalf of women who have taken Lipitor and who have no history of heart disease or diabetes; people aged 65 and over who have taken Lipitor and who have no history of heart disease or diabetes; and third-party payers such as insurance companies, union health and welfare funds, self-insured employers and others, who paid for Lipitor for patients in these groups.
The lawsuit alleges that the success of Lipitor is due in large part to a deceptive advertising and promotional campaign to convince doctors and patients alike that Lipitor reduces heart disease and heart attacks for nearly everyone with elevated cholesterol.
The lawsuit claims Pfizer misled consumers into using Lipitor despite the absence of evidence that the drug is of any benefit to large segments of the population and promoted Lipitor by claiming it prevents heart disease in women and the elderly, where no clinical test has established such a benefit. And in fact, according to the complaint, women in a study without heart disease actually suffered 10% more heart attacks while taking Lipitor, than women who received a placebo.
The plaintiffs allege that as a result of a deceptive marketing campaign, Pfizer created an artificial demand for Lipitor which would not have existed had there been full and fair disclosure regarding the lack of evidence proving a relationship between Lipitor and a reduced risk of heart disease.
The complaint alleges that Pfizer violated state consumer protection laws against deceptive advertising and seeks reimbursement for persons who bought Lipitor needlessly as a result of Pfizer's marketing and promotional campaign.
"We believe Pfizer intentionally ignored the scientific evidence -- and lack thereof -- and launched a multi-million dollar ad campaign designed to push the drug to anyone they could convince to buy it," said Steve Berman, the lead attorney in the case, to Consumer Affairs on September 29, 2005.
"We intend to prove in this case that Pfizer's false advertising created an enormous artificial demand for Lipitor," he said, "much of which would not exist if Pfizer had fully and fairly disclosed the truth about the drug."
"We intend to prove that Pfizer pocketed billions in sales to those who do not benefit from Lipitor," he told Consumer Affairs.
Critics point out that the over-prescribing of Lipitor comes at a high cost to taxpayers. "We all pay the price for the over-prescription of drugs, like Lipitor, because we have to foot much of the bill for state pharmacy programs for seniors," said Melissa Shannon, Consumer Health Policy Coordinator of Health Care For All.
"We can't allow drug companies," she warns, "to trick seniors into taking expensive, unnecessary drugs that will drive up the already-high costs that Medicare will be paying for seniors' drugs."
For the purpose of the lawsuit, member of the class include:
- All women in the United States without previously medically diagnosed heart disease or diabetes who have taken and paid out of pocket for Lipitor in the last four years;
- All female or males in the United States without previously medically diagnosed heart disease or diabetes who have taken and paid out of pocket for Lipitor in the last four years and who did so while over the age of 65.
- Third-Party Payors (health plans, union benefit funds, self-insured employers and others) who paid for Lipitor used by the patients described above.
On thing is certain, Pfizer attorneys will not be seen in the unemployment lines anytime soon. According to Pfizer's May 8, 2006 SEC Filing, since March 2006, a number of purported class actions have been filed against Pfizer in various federal courts alleging claims relating to the promotion of Lipitor.
"The plaintiffs allege that," the filing states, "through patient and medical education programs and other actions, the Company promoted Lipitor for use by certain patients contrary to cholesterol guidelines, which are referenced in the product labeling, that recommend changes to diet and exercise."
According to Pfizer, the plaintiffs seek to represent nationwide and certain statewide classes consisting of health and welfare funds and other third-party payors that purchased Lipitor for such patients or reimbursed such patients for the purchase of Lipitor since January 1, 2002.
"Each of the actions alleges, among other things," Pfizer states in the report, "fraud, unjust enrichment and the violation of the federal Racketeer Influenced and Corrupt Organizations Act ("RICO") and certain state consumer fraud statutes and seeks monetary and injunctive relief, including treble damages."
The filing is no doubt referring to a class action lawsuit filed against Pfzer in late March 2006, by the Welfare Fund of Teamsters Local Union 863 in US District Court in Newark, NJ, that accuses the company of marketing Lipitor for off-label uses not included in the federal guidelines.
The aggrieved plaintiffs are insurance companies and drug benefit plans that paid for off-label prescriptions that, according to the lawsuit, might not have been written if Pfizer had not marketed Lipitor off-label illegally.
In a nutshell, the lawsuit says Pfizer has been promoting the use of Lipitor for cholesterol levels that are below those specified in the guidelines in the Third report of the Adult Treatment Panel, developed by the National Cholesterol Education Panel, which is a panel of the National Heart, Lung, and Blood Institute (ATP III).
To that end, the lawsuit says Pfizer influenced doctors to prescribe Lipitor to patients with cholesterol levels lower than the guidelines recommend. Or simply put, Pfizer sold Lipitor to patients who did not need it.
The suit relies on the federal Racketeer Influenced and Corrupt Organizations Act (RICO) to build a national class of defrauded third-party payers, but in case the RICO class fails, the plaintiffs' lawyers say they are filing additional state lawsuits.
According to plaintiffs attorney, Geoffrey Jarvis, of Grant and Eisenhofer, in an interview with Pharmaceutical Executive on March 29, 2002, the law suit is about the low-risk people, those that have less than a 10% chance of contracting coronary heart disease in the next five years.
"For that group of people," he says, "according to the drug label, unless their cholesterol is above 160, statin drug therapy is not recommended."
The plaintiffs claim that Pfizer worked to get physicians to prescribe Lipitor to people with a low risk of heart disease and cholesterol levels below 160. "There are about 15 million people in that group," Mr Jarvis said in the interview. "Basically, they are trying to expand the market of the drug to people who really ought to not be on it."
The complaint also alleges that Pfizer misrepresented Lipitor's potential market to investors by claiming "millions more potential patients than would be expected under the government guidelines."
The complaint states that "Pfizer also employed purported 'independent' third parties ... to promote Lipitor's off-label use."
In addition to paid consultants and marketing firms, it says, the company engaged organizations such as Emerging Science in Lipid Management and the National Lipid Education Council to offer physicians continuing medical education courses as well as to publish articles extolling Lipitor's off-label usage.
The complaint claims, "both organizations are fully funded by Pfizer" and have become an active part of the marketing plan for Lipitor.
Critics are quick to point out that the off-label scheme described in the current complaint resembles the charges in the fraud case that Pfizer lost in 2004 where the company paid a $430 million penalty for promoting and marketing the epilepsy drug, Neurontin, for off-label uses not approved by the FDA.
"Once you connect the dots and see the elaborate sophistication and reach of Pfizer's plan to go way beyond the federally mandated guidelines for prescribing Lipitor, there is no other way to describe it except as a fraudulent scheme, whose true purpose has been to extract illegal payments from third-party payors for Lipitor's off-label use," said Jay Eisenhofer of Grant & Eisenhofer in explaining the racketeering claims, on the Freight Teamster's Web sit.
"Between the company's own off-label marketing and the coordinated campaign by its various consultants and captive physician education groups, Pfizer has reaped billions of dollars in insurance payments to cover prescriptions for patients for whom Lipitor therapy is not recommended under FDA approved usage standards," Mr Eisenhofer noted.
The drug plan plaintiffs allege that Lipitor's dramatic rise in sales from $5 billion in 2000 to $12.1 billion in 2005, is a direct result of Pfizer's off-label promotion of the drug during that period.
"This is a classic case of unjust enrichment," Mr Eisenhofer said. "Pfizer has built colossal sales of Lipitor through the pipeline of third-party payors such as our clients and countless other drug plans - including Medicaid and Medicare - much of it based on prescriptions that the FDA's guidelines say never should have been written in the first place."
Analysts predict that more suits of this kind are on the horizon. "States are going to tighten up this sort of thing because it's a way to control Medicare costs," Les Funtleyder, an analyst for Miller Tabak told CNN Moneyline on March 28, 2006.
"If suits like this start proving to be successful," he said, "then you'll start to see a cascade effect."
The list of initial plaintiffs participating in the class action include:
- Welfare Fund of Teamsters Local Union 863 (New Jersey)
- Southern Illinois Laborers and Employers Health and Welfare Fund
- Midwestern Teamsters Heath & Welfare Fund (Illinois)
NECA-IBEW Health and Welfare Fund (Illinois)
Cleveland Bakers and Teamsters Health and Welfare Fund (Ohio)
- Electrical Workers Benefit Trust Fund (Indiana)
Sidney Hillman Health Center of Rochester (New York State)
According to the Justice Department, the unreported discounts allowed the company to retain more than $20 million in rebates owed to Medicaid.
And for what it is worth, which apparently is nothing, in addition to the $20 million payment, the Justice Department said, Pfizer agreed to a 5-year corporate integrity agreement intended to prevent future problems.
The agreement is especially funny in light of the fact the company was busted for false advertising a month earlier in September 2002, when the FDA instructed Pfizer to immediately pull all magazine advertisements that claimed Lipitor caused fewer side effects than the other statin drugs.
According to the FDA, the ads appearing in magazines such as Reader's Digest and Time indicated that Lipitor "lacks" the side effects of other cholesterol drugs and claimed that other drugs in Lipitor's class of medications may cause a severe debilitating muscle condition.
The ads were knowingly false and misleading because at the time, Lipitor's own label stated that all statins increased a patient's chance of developing myositis and rhabdomyolysis, potentially fatal conditions that cause muscle pain and muscle deterioration, and may lead to kidney failure symptoms.
However, it appears that Pfizer's conduct of concealing and minimizing side effects has come back to haunt the drug maker. In June 2006, two men filed personal injury lawsuits against Pfizer, alleging that the company concealed serious health risks associated with Lipitor.
The lawsuits accuse Pfizer of promoting Lipitor as a safe drug and failing "to inform consumers and the medical profession of serious side effects associated with the statin Lipitor," according to a statement released by plaintiff attorney, Mark Krum.
Both plaintiffs, Charles Wilson, 60, a former insurance executive, and Michael Mazzariello, 47, an attorney from New York, filed their lawsuits in New York State Supreme Court.
Although they filed separate actions, each man is charging that Lipitor caused extensive memory loss, irreparable nerve damage, and bouts of fatigue.
Three years after terminating use of the drug, Mr Wilson says he continues to suffer from loss of balance, fatigue, and burning sensations in his hands and feet.
And, according to the lawsuit, Mr Mazzariello, who took the drug for only two months, has suffered debilitating nerve and muscle injury, has endured repeated hospitalizations, and now walks with a cane.
But Pfizer's latest marketing trick beats anything described above. According to Bloomberg News on August 24. 2006, Pfizer said that it had increased second-quarter revenue from Lipitor by persuading doctors to prescribe higher doses of the drug.
Pfizer says it sent thousands of sales people to doctors' offices to tout studies showing that higher doses cut the risks of heart attack, stroke and death, better than other cholesterol drugs.
As a result of selling more of the higher priced pills, Lipitor revenue increased by 2% to $3.1 billion in the second quarter, even though about the same number of patients took the drug, according to Pfizer.
The number of patients taking the highest doses in June rose by more than 10% compared with May. A 10 milligram Lipitor pill costs $2.44, while the 40 and 80 milligram doses are $3.33 each, or 36% more, according to the Drug Store.com web site.
Some heart experts say that the company's promotion may spur doctors to prescribe higher doses for everyone, even though the majority of patients do not need them, according to Steven Findlay, an analyst for Consumers Union, a nonprofit company that publishes Consumer Reports magazine.
To give this story a happy ending that indicates drug makers can not keep getting away with murder forever, its worth noting that on March 28, 2006, the Wall Street Journal reported that federal prosecutors were reviewing Pfizer's alleged off-label marketing "because of the billions of dollars spent on Lipitor every year by Medicaid and the states."
On the same day that the Journal ran its article, Pfizer acknowledged to CNN Moneyline, that an investigation had been initiated against the company by the US Attorney's office in Brooklyn, New York, reportedly because of marketing practices.