For more than a decade, cardiologists treating patients who have had a heart attack have routinely scribbled one drug onto their prescription pads: clopidogrel bisulfate, better known as Plavix.

“It’s a mainstay,” said Dr. Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic.

Before Plavix arrived in 1997, aspirin was the standard treatment for preventing blood clots that led to heart attacks and stroke. Combining aspirin with Plavix, though, “tremendously improved” the results, Nissen said.

But now, in a farewell that has been years in the making, the story of Plavix is coming to an end. The drug is set to lose its patent protection today. Faced with an expected influx of cheaper generic alternatives, Bristol-Myers Squibb, which sells Plavix in the United States under a partnership with Sanofi-Aventis, has said it no longer plans to actively promote the drug.

“This is one of the behemoth drugs that really defined the drug industry in the ’90s,” said Catherine Arnold, an analyst for Credit Suisse.

Bristol-Myers is hardly the only company to face the loss of a best-selling drug: At least 19 are set to lose patent protection this year, which is expected to cost the pharmaceutical industry about $38.5 billion in lost sales, according to an analysis by Barclay’s. About 80 percent of U.S. prescriptions are now filled with generic drugs.

The loss of the company’s top product is sure to sting. Plavix brought in $7.1 billion in net sales in 2011, accounting for a third of revenue for the year, according to Bristol-Myers filings. In the 15 years since it entered the market, Plavix generated $42.8 billion in sales for Bristol-Myers, according to IMS Health, a health care services company. It is the biggest name-brand drug to lose patent protection since Lipitor, made by Pfizer, encountered generic competition late last year.

‘Pharmageddon’

With the loss of patent protection for Plavix and Lipitor coming in such quick succession, “this year is a year that pharmaceutical insiders refer to as ‘pharmageddon,’” Nissen said.

But while Pfizer moved to retain its market share of Lipitor for as long as possible — by selling its own authorized generic version and negotiating aggressive deals with insurers and pharmacy benefit managers to match or beat the price of generic alternatives — Bristol-Myers has said it has no plans to hold onto Plavix, other than to offer a limited-time discount plan for patients who wish to continue with the brand-name drug. The company stopped running television advertisements in June.

“We expect a rapid, precipitous and material decline in Plavix net sales,” company officials wrote in the 2011 annual report.

Analysts expect the price of generic alternatives to be substantially lower than Plavix.

Usually, drug prices take several months to drop because one generic company — the first to file an application with the drug agency — is granted the exclusive right to market the drug for the first six months. But Plavix is different because the company that won that right, the Canadian drugmaker Apotex, forfeited its exclusive period after it flooded the market in 2006 with unauthorized generic versions of the drug.

In what amounted to a dress rehearsal for this year, Plavix lost an estimated $1 billion in sales when Apotex, which had challenged the drug’s patent, managed to distribute a six-month supply before a judge ordered the company to stop.

Negotiations with Apotex over the patent also landed Bristol-Myers in trouble with federal authorities. Bristol-Myers ultimately paid more than $3 million in civil and criminal fines after the Justice Department claimed it had entered into a secret deal with Apotex to delay offering its own generic version of the drug during Apotex’s exclusivity period. A former Bristol-Myers senior vice president pleaded guilty to making a false statement to the government in the case.

Other generics

Because Apotex lost its exclusivity, seven companies have received tentative approval to market the generic drug. Dr. Reddy’s Laboratories received approval in 2008 to market a 75-milligram dose, but it has been prevented under a court order from selling the drug. The agency often, but not always, gives final approval to generic drug companies on the day the brand-name drug loses patent protection.

Uday Baldota, a spokesman for Sun Pharmaceutical Industries, an Indian drugmaker that has received tentative approval to sell generic Plavix, said his company often planned for the introduction of a new drug seven to eight years ahead of time, with the goal of shipping the new drug “as soon as the patent expires,” he said in an email. Once the company receives final approval, the plan unfolds with extreme precision, he said. “I would not be surprised if there was a stopwatch involved!”

A spokeswoman for the large drug distributor Cardinal Health said the company planned to begin shipping generic Plavix Friday.

Life beyond Plavix

Analysts have largely credited Bristol-Myers with successfully planning for its future after Plavix. In recent years, it has moved away from its primary care business and into specialty pharmaceuticals, using cash from the sales of smaller business units to finance the purchase of several small biotechnology firms.

Last year, the company won approval of a drug to treat melanoma, Yervoy. In June, the Federal Drug Administration is expected to decide on approval of a blood-thinning drug, Eliquis, that Bristol-Myers is developing in partnership with Pfizer. Eliquis belongs to a new class of drugs intended to help prevent strokes in people with the heart arrhythmia known as atrial fibrillation. If approved, analysts expect it to bring in billions of dollars in revenue.

“It really turned out to not just be rhetoric,” Arnold of Credit Suisse said. “They really have created a confidence in investors that there is life beyond Plavix.”