Merck & Co.’s Vioxx painkiller may have caused as many as 140,000 heart attacks in the U.S. before it was withdrawn Sept. 30, Food and Drug Administration safety reviewer David Graham said in a study published online today by the British medical journal Lancet.
The study was based on records of 1.4 million members of Kaiser Permanente, the largest U.S. nonprofit insurer, with 6 million members in California. Researchers compared the incidence of heart attacks and sudden cardiac death for patients taking Vioxx with those on Pfizer Inc.’s similar Celebrex and over-the-counter pain medications.
Applying the findings across the U.S. population, “we arrived at the estimate of 88,000 to 140,000 patients that had a heart attack in the U.S. because they used Vioxx,” Graham, 50, said in a telephone interview yesterday. The drug was introduced in 1999.
Portions of the study were disclosed earlier, starting with a medical conference in August. The U.S. regulatory agency published some of the findings in November, and Graham said in Nov. 18 testimony before the Senate Finance Committee that between 88,000 and 139,000 heart attacks may have been linked to Vioxx.
Merck, the world’s third-biggest drugmaker, withdrew Vioxx after a company study showed that patients taking it for 18 months or longer had twice the risk of heart attacks and strokes 1.5 percent as those taking a placebo.
U.K., U.S. Inquiries
Merck’s announcement of the Vioxx withdrawal, the biggest drug recall ever, wiped out almost $27 billion of the stock’s market value Sept. 30. Shares of Whitehouse Station, New Jersey based Merck fell 51 cents to $29.85 as of 4:17 p.m. New York time yesterday in New York Stock Exchange composite trading.
The Vioxx withdrawal led U.K. and U.S. regulators to call meetings to scrutinize the risks of painkillers. Graham declined to comment on the FDA’s advisory panel meeting next month. The U.S. Senate’s finance and health committees and the House Energy and Commerce Committee are investigating whether Merck and the FDA failed to protect U.S. consumers from Vioxx.
Graham’s research as published by Lancet was revised for quality control and to remove a handful of cases, Graham said yesterday. The study was originally to be published online in Lancet Nov. 17, Graham said. He said FDA managers at one point threatened to fire him as associate director for science and medicine in the agency’s Office of Drug Safety if he published the findings.
The study found that Vioxx, given at the standard dose, increases the risk of heart attack by about 50 percent, compared with Pfizer’s Celebrex, and more than triples the risk of heart attacks when given at high doses. The two drugs suppress the body’s production of the Cox-2 enzyme, which is linked to pain and swelling.
People taking Vioxx had a 34 percent higher chance of heart disease compared with those taking other painkillers including Celebrex, naproxen and ibuprofen, the study found.
Patients taking naproxen, a generic painkiller sold as Aleve by Bayer AG, had a 14 percent increase in heart risk compared with some other painkillers such as ibuprofen, the study showed. Previous trials suggested naproxen may protect against cardiac disease.
Almost 18 percent of the 106.7 million prescriptions for Vioxx were for the highest dose, the study in Lancet said. About 20 million people in the U.S. tried the drug since its 1999 introduction, according to Merck, the second-biggest U.S. drugmaker.