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Acetyl salicylic acid（ASA）was synthesized by Felix Hoffman in 1897 to reduce the unbearable gastric side effects of patients treated with high doses of salicylic acid. For many years, together with other newly synthesized NSAIDs, ASA was used as an antirheumatic agent. It was not until Sir John Vane in 1971, when it was discovered that these compounds acted through inhibition of prostaglandins and thromboxanes. The road of NSAIDs, and overall ASA, to the present time has been long and exciting. ASA high-dose is now used only short-term to treat cold and fever, but it is massively used long-term, at very low doses（80-100 mg/day）, to prevent cardiovascular events due to its ability to inhibit irreversibly the COX-1 isoenzyme in platelets and the prothrombotic agent thromboxane. This benefit occurs at the expense of an increased incidence of gastrointestinal bleeding, an adverse event shared and increased by dual COX（COX-1 and COX-2）inhibitor NSAIDs. NSAIDs are used worldwide to treat pain and rheumatism. In order to reduce GI adverse events and avoid inhibition of mucosal prostaglandins derived from constitutive COX-1 enzyme, COX-2 selective inhibitors where developed. These agents have a reduced risk of inducing damage to both the upper and the lower GI tract. Furthermore, experimental, clinical and epidemiological data suggested that these agents could prevent GI and colon cancer, since COX-2 overexpression in tumors was seen as chemo-preventive target. Lon-term colonic polyp prevention trials showed that these agents have that effect, but also increased the risk of CV events due to, at least in part, inhibition of the COX-2 derived antithrombotic prostacyclin, an effect also seen with other dual COX inhibitor NSAIDs. More recently, low-dose ASA aspirin has been proven to be associated with reduction of gastrointestinal cancer, especially colon cancer, risk. The mechanisms by which this drug acts at this level is not well understood, but mechanistically its effect could be due largely to its antiplatelet activity, which would also explain its ability to reduce distant metastases of colon cancer. Research and new indications for this drug continues to expand 106 years after its discovery, which makes ASA a unique and extraordinary drug. |
