Vioxx caused up to 140,000 heart attacks — Merck paid $4.85B to settle

Vioxx (rofecoxib) was a COX-2 inhibitor approved by the FDA in May 1999 for arthritis and acute pain. It became one of the most prescribed drugs in the world, with annual sales of $2.5 billion at its peak. Merck marketed it as a safer alternative to older NSAIDs because it caused fewer gastrointestinal side effects. But the VIGOR study, published in 2000, found a 4.25-fold increase in heart attacks compared to naproxen — a finding Merck dismissed as a statistical artifact.

Merck withheld the cardiovascular risk data from doctors and patients for over four years. The APPROVe study, an Alzheimer's prevention trial, was terminated early in 2004 when it confirmed a 1.92-fold increase in thrombotic events after 18 months of use. On 30 September 2004, Merck voluntarily withdrew Vioxx worldwide. An FDA analyst later estimated that Vioxx may have caused 88,000 to 140,000 serious cardiovascular events in the US alone, 30–40% of them fatal.

Merck faced over 27,000 lawsuits. In November 2007, the company agreed to a $4.85 billion settlement covering most claims. In 2011, Merck paid an additional $950 million to settle civil claims with US authorities and pleaded guilty to a federal misdemeanor, incurring a $321.6 million fine. The Vioxx scandal permanently changed how COX-2 inhibitors and NSAIDs are labelled and prescribed, and it remains one of the largest drug safety scandals in history.