But a 1996 study showed Lipitor reduced bad cholesterol dramatically more than the other statins, from the very start of treatment and even more so over time. A striking graph of those results helped Lipitor sales representatives turn it into the world's best-selling drug ever, with more than $125 billion in sales over 14½ years.
Nicknamed "turbostatin," Lipitor became the top-selling statin barely three years after it was launched. It's provided 20 percent to 25 percent of Pfizer Inc.'s annual revenue for years.
But after nearly a decade as the top-selling drug, Lipitor is set to be toppled in 2012 after getting its first generic rivals four weeks ago.
It's a run not likely to be repeated.
Back in the early 1980s, the public was just starting to learn what cholesterol was. There was little evidence that controlling it with medication could be so crucial in preventing disability and early death, and the coming epidemic of obesity and diabetes in an aging population wasn't foreseen.
At the time, heart attack prevention basically amounted to telling patients to eat more oatmeal and skip the steak.
Lipitor creator Warner-Lambert, a midsize drugmaker best known for consumer health products, including Listerine, Benadryl allergy pills and Halls cough drops, got a late start in what turned into a surprisingly fast-growing market.
Merck & Co. had a decade lead with Mevacor, launched in 1987. By 1994, its successor drug, Zocor, along with Bristol-Myers Squibb Co.'s Pravachol and Novartis AG's Lescol, had crowded the market.
"Those other companies didn't even take us seriously. They didn't think we could be a viable contender," said Adele Gulfo, then head of cardiovascular marketing at Warner-Lambert Co. who now heads Pfizer's primary-care drugs business.
Doctors said they were "quite satisfied with the medicines we have," she recalled recently.
Given that, marketing executives at Warner-Lambert were projecting Lipitor sales of $300 million a year at best, recalls the drugs's inventor, chemist Bruce Roth.
"I wish someday you guys could make us a drug we could sell," the marketers told his team, recalls Roth, a research vice president for Genentech, a biotech pioneer now owned by Swiss drugmaker Roche.
They had, but didn't see it.
"There was a lot of controversy at Warner-Lambert as to whether we should even take our molecule into the clinic" for human testing, Roth says. "It was kind of a big risk. ... It's millions of dollars."
But senior management was persuaded in 1990 to at least fund the initial round of testing on a couple of dozen employee volunteers.
The results were far better than what had been seen in the animal tests.
"It tremendously, incredibly outperformed the other statins," Roth says. "It was as good at its lowest dose as the other statins were at their highest dose."
So Warner-Lambert partnered with much-larger Pfizer Inc., considered the industry's top marketer, first to help fund the expensive late-stage testing of the drug in people and then to promote Lipitor after it was launched. Pfizer bought out Warner-Lambert in 2000 to block two other companies trying to acquire it and get control of Lipitor.
Pfizer benefited from some lucky timing: Lipitor went on sale in 1997, the year the Food and Drug Administration first allowed drug ads targeting consumers.
So Pfizer spent tens of millions on ads, including on the popular drama "ER," first urging patients to "Know Your Numbers" and then showing patients discussing how Lipitor helped them get their cholesterol numbers below guideline goals.
Meanwhile, health groups kept lowering the cholesterol targets in national guidelines, making millions more patients good candidates for statin treatment, as new research showed the link between cholesterol levels and consequences such as heart attacks. All those new patients boosted sales for the whole statin class, particularly Lipitor.
The Lipitor promotion team set new standards for a marketing campaign. They repeatedly visited family doctors as well as cardiologists, and blanketed patients with data showing that Lipitor was best at lowering cholesterol. They stressed to doctors nervous about safety that Lipitor's lowest dose worked as well as rivals' highest doses. They gave free samples of the white pills and sometimes bought lunch for the office staff.
The company continued research on Lipitor, through this year conducting more than 400 studies, costing roughly $1 billion and including more than 80,000 patients. The studies have shown how Lipitor helped patients with heart problems, diabetes, stroke risk and other conditions, by preventing heart attacks and strokes and reducing plaque buildup in arteries.