Let's do the time warp: Vioxx v. opioids

In 1999, Merck & Co. introduced Vioxx (rofecoxib), a COX-2 selective nonsteroidal antiinflammatory drug (NSAID). NSAIDs are among the most widely used medications that reduce inflammation, relieve pain, and lower fever by inhibiting enzymes (COX-1 and COX-2). You may know them as ibuprofen, naproxen, and aspirin. While effective for managing conditions like arthritis and acute pain, NSAIDs carry risks of gastrointestinal bleeding, kidney damage, and in some cases, cardiovascular events, particularly with long-term use or in individuals with preexisting conditions.

Unlike traditional NSAIDs, Vioxx targeted the COX-2 enzyme associated with inflammation over COX-1, which protected the stomach lining leading to fewer gastrointestinal side effects. Vioxx became a blockbuster for Merck, generating $2.5 billion in annual sales until its success unraveled when evidence of cardiovascular risks emerged. In 2000, the VIGOR (Vioxx Gastrointestinal Outcomes Research) trial, revealed a troubling increase in heart attacks among Vioxx users compared to naproxen users. Merck initially attributed the findings to naproxen's cardioprotective effects.

In 2004 a Merck-sponsored study confirmed a doubled risk of heart attacks and strokes for patients taking Vioxx for more than eighteen months. Merck voluntarily withdrew Vioxx that year. Enter oxycodone.

I asked ChatGPT to run numbers comparing public health outcomes under the NSAID and opioids. A systematic review in The Lancet and CDC reports indicate that twenty-one to twenty-nine percent of chronic pain patients prescribed opioids misuse them, and eight to twelve percent develop opioid use disorder (OUD). The overdose death rate for long-term opioid users is estimated at five per one thousand for prescription opioids, per a JAMA 2018 study.

The Horizon presents a hypothetical one-thousand-patient panel. Assuming all patients are prescribed opioids for chronic pain over a year, which are the treatment for moderate to severe pain, eighty to one-hundred-twenty patients will develop opioid use disorder, with five deaths caused by opioid overdose.

Vioxx, for moderate pain, compared favorably. Assuming all patients take Vioxx for chronic pain over a year, they will experience three to four additional heart attacks or strokes. The estimated fatality rate of cardiovascular events is approximately twenty to thirty percent. This translates to one death per one thousand from Vioxx-related events, compared to five treated with opioids.