Text: Bertrand Tappy

Every molecule tells a story: acetylsalicylic acid

Everyone knows what aspirin is. But acetylsalicylic acid, its scientific name, has sparked much debate.

Anti-inflammatory agents are derived from the bark of willow trees. The plant’s effectiveness in reducing fever and pain has been recognised since the time of ancient civilisations. In the 19th century, scientists in both France and Germany purified the active ingredient responsible for this therapeutic action, salicylic acid.

Salicylic acid is effective in relieving pain, but upsets the stomach. In 1904, Felix Hoffmann, a chemist working at the pharmaceutical group Bayer, developed a method of producing acetylsalicylic acid that causes significantly less irritation to the stomach and only releases salicylic acid once it is absorbed into the bloodstream. This advance led to the commercial development of a drug a few years later, patented as Aspirin (its name was derived from acetylation and spiric acid).

Aspirin soon became a huge success as a pain reliever and anti-inflammatory drug. But another effect eventually surfaced: Aspirin caused bleeding. Surgeons reported that patients treated with aspirin lost more blood during surgery. The medical community then examined how this action could benefit patients with arterial thrombosis, especially in the coronary arteries. In 1975, one of the very first “randomized, double-blind” studies was published, demonstrating aspirin’s preventive effectiveness following a myocardial infarction. Half of the heart attack patients received a daily dose of 300 mg of aspirin and the other half an inert placebo. The results confirmed the hypothesis. With its antiplatelet effect, aspirin prevented subsequent heart attacks. It was a major discovery, since in the 1970s, heart attack patients had a one in ten chance of having another heart attack and dying within the year! Aspirin reduced this risk to one in 13. In other words, 40 patients would have to be treated for one year to prevent one death (while three will still die with the aspirin, instead of four without aspirin).

At first, heart patients were given the same dose as that given for pain relief. Over time and with a lot of perseverance, physicians managed to convince their colleagues to use lower doses administered over a long period of time to prevent blood clots. Today, more than 30 years later, doses of 100 mg or less are given to patients with a risk of heart attack and stroke. “It’s not surprising,” says Thierry Buclin, chief of the Clinical Pharmacology Division at Lausanne University Hospital. “Many other drugs have been administered at a dosage that was too high when they were first released, including the contraceptive pill, antipsychotic medicines, diuretics and anti-cancer drugs. Using high doses early on guarantees effectiveness for and against everything. It takes longer to figure out how to optimise safety in administering them.” Isn’t it contradictory then that pharmacies sell 500 mg of aspirin over the counter, while the 100 mg dose used to treat heart patients is only available with a prescription? ⁄