efficient methods of synthesis. In 1897, scientists at the drug and dye firm Bayer began investigating acetylsalicylic acid as a less-irritating replacement for standard common salicylate medicines, and identified a new way to synthesize it. By 1899, Bayer had dubbed this drug Aspirin and was selling it globally. The word Aspirin was Bayer's brand name, rather than the generic name of the drug; however, Bayer's rights to the trademark were lost or sold in many countries. Aspirin's popularity grew over the first half of the 20th century leading to fierce competition with the proliferation of aspirin brands and products. Aspirin's popularity declined after the development of acetaminophen/paracetamol in 1956 and ibuprofen in 1962. In the 1960s and 1970s, John Vane and others discovered the basic mechanism of aspirin's effects, while clinical trials and other studies from the 1960s to the 1980s established aspirin's efficacy as an anti-clotting agent that reduces the risk of clotting diseases. The initial large studies on the use of low-dose aspirin to prevent heart attacks that were published in the 1970s and 1980s helped spur reform in clinical research ethics and guidelines for human subject research and US federal law, and are often cited as examples of clinical trials that included only men, but from which people drew general conclusions that did not hold true for women. Aspirin sales revived considerably in the last decades of the 20th century, and remain strong in the 21st century with widespread use as a preventive treatment for heart attacks and strokes. Trademark Bayer lost its trademark for Aspirin in the United States in actions taken between 1918 and 1921 because it had failed to use the name for its own product correctly and had for years allowed the use of "Aspirin" by other manufacturers without defending the intellectual property rights. Today, aspirin is a generic trademark in many countries. Aspirin, with a capital "A", remains a registered trademark of Bayer in Germany, Canada, Mexico, and in over 80 other countries, for acetylsalicylic acid in all markets, but using different packaging and physical aspects for each. Compendial status United States Pharmacopeia British Pharmacopoeia Medical use Aspirin is used in the treatment of a number of conditions, including fever, pain, rheumatic fever, and inflammatory conditions, such as rheumatoid arthritis, pericarditis, and Kawasaki disease. Lower doses of aspirin have also been shown to reduce the risk of death from a heart attack,