Vioxx (rofecoxib) — Merck’s Heart-Attack Painkiller Pulled in 2004, $4.85 Billion Paid

When Merck & Co. pulled Vioxx from pharmacy shelves worldwide on 30 September 2004, chief executive Raymond Gilmartin framed it as a responsible company acting on new data; the documented record shows a five-year gap between that posture and what the company’s own clinicians had measured. Vioxx (rofecoxib), a COX-2 selective anti-inflammatory approved by the U.S. Food and Drug Administration on 20 May 1999 and marketed as a gentler painkiller that spared the stomach, was instead associated with one of the largest drug-safety catastrophes in regulatory history. FDA drug-safety reviewer David Graham would testify to the Senate Finance Committee on 18 November 2004 that the drug had caused on the order of 88,000 to 139,000 excess heart attacks and strokes in the United States, of which perhaps 30 to 40 percent were fatal — a toll he compared to between two and four jumbo-jet crashes a week sustained over five years.

The gap between promise and reality was not discovered late; it was visible in Merck’s own trials. The VIGOR study, published in The New England Journal of Medicine on 23 November 2000 under lead author Claire Bombardier, showed that the 8,076 patients taking rofecoxib had roughly four to five times the rate of myocardial infarction of patients taking the older drug naproxen — a relative risk the published paper reported as 0.2 in naproxen’s favor. Merck attributed the difference to a supposed protective effect of naproxen rather than a cardiac hazard of Vioxx — a hypothesis that was never proven and that the company continued to advance while sales climbed past $2.5 billion a year and a sales force of more than 3,000 representatives carried the message to prescribers.

The withdrawal came only when the harm became impossible to explain away. The APPROVe trial — designed to test whether Vioxx prevented recurrent colon polyps, not to study the heart — was halted early on 23 September 2004 after showing that rofecoxib roughly doubled the risk of confirmed cardiovascular events after eighteen months of use, against placebo. The verdict here is therefore plain at the outset: an approved, heavily advertised, trusted medicine reached tens of millions of patients while the signal that would eventually condemn it sat in the company’s data, the FDA’s review files, and the medical literature, fully legible to anyone with access and the will to read it.

What followed was the largest pharmaceutical mass-tort reckoning of its era. In November 2007 Merck agreed to pay $4.85 billion to resolve roughly 27,000 lawsuits covering some 47,000 plaintiff groups, NEJM issued a formal “Expression of Concern” alleging the VIGOR authors had withheld cardiac data, and the case became the standard byword for how surrogate-endpoint approval, aggressive marketing, and suppressed safety signals can converge into mass harm before any regulator pulls the cord.