Timeline of major regulatory events and other key historical timepoints of US NSAID history
| Year | Event |
| 1900 | Aspirin registered in the USA, available via prescription.70 |
| 1915 | Aspirin approved by FDA for OTC distribution.71 |
| 1964–1976 | Indomethacin, ibuprofen, diclofenac, ketoprofen and naproxen approved by the FDA.72 73 |
| 1971 | John Vane discovered the mechanism of action of aspirin and other NSAIDs.74 |
| 1976 | COX enzyme was discovered, recognised for its role in prostaglandin synthesis.74 |
| 1984 | Ibuprofen approved by FDA for OTC distribution.75 |
| 1985 | FDA approved aspirin for treatment of acute myocardial infarction and secondary cardiovascular prevention, CDC endorses.76 |
| 1991 | Second COX enzyme (‘COX-2’) was discovered, recognised as identical in structure but having important differences in substrate and inhibitor selectivity and in intracellular locations.77 |
| 1999 | Celecoxib, the first selective COX-2 inhibitor, is available via prescription.78 |
| 2004–2005 | Selective COX-2 inhibitors (rofecoxib and valdecoxib) were withdrawn from the market based on evidence that long-term use increases cardiovascular risk. Celecoxib remained on the market with a black box warning. The warning was also added to the OTC NSAIDs’ drug facts label.30 |
| 2007 | FDA approved topical diclofenac at the prescription-level.79 |
| 2015 | Strengthening of the black box warning OTC NSAIDs’ drug facts labels related to risk of heart attack and stroke.14 |
| 2016 | The USPSTF recommends initiating low-dose aspirin use for the primary prevention of CVD and CRC in adults aged 50–59 years (B recommendation).80 |
| 2020 | Topical diclofenac approved for OTC distribution.28 |
| 2022 | Department of Health and Human Services initiates the Million Hearts Campaign, a national initiative to prevent 1 million heart attacks and strokes within 5 years. It focuses on implementing a set of evidence-based priorities that can improve cardiovascular health (including appropriate aspirin use).81 |
| 2022 | The USPSTF recommends that for adults aged 40–50 years with an estimated 10% or greater 10-year CVD risk: The decision to initiate low-dose aspirin use for the primary prevention of CVD in this group should be an individual one (C recommendation).82 |
CDC, Centres for Disease Control and Prevention; COX, cyclooxygenase; CRC, colorectal cancer; CVD, cardiovascular disease; FDA, Food and Drug Administration; NSAIDs, nonsteroidal anti-inflammatory drugs; OTC, over-the-counter; USPSTF, United States Preventive Services Task Force.