Acetylsalicylic Acid (Aspirin): Past, Present, and Future

Acetylsalicylic acid is the most common antithrombotic drug, which started its pharmacological journey as a non-steroidal, anti-inflammatory drug. When used as a low-dose drug (of 75-100mg) once per day, it irreversibly inhibits prostaglandin H synthase, commonly termed cyclooxygenase 1 or COX-1 enzyme, which is acetylsalicylic acid's molecular drug target in human platelets. This mechanism of action ensures that the inhibition of the pro-aggregatory prostanoid - thromboxane A2 synthesis is achieved permanently in platelets throughout their lifespan, which is responsible for acetylsalicylic acid's antithrombotic effect. In this literature review, we provide an overview of acetylsalicylic acid's development through history, the current understanding of the molecular mechanism of its action, as well as the resulting side effects impacting different tissues due to its control of the arachidonic acid metabolism and prostanoid synthesis in them. In an effort to begin a dialogue regarding the evidence in favor of unresponsiveness to acetylsalicylic acid's therapeutic effect in specific patients, we describe already identified molecular mechanisms of resistance to acetylsalicylic acid and list the existing biomarkers which are able to quantifiably measure the achieved degree of acetylsalicylic acid's clinical efficacy. Furthermore, we look to the future by encouraging a personalized approach to acetylsalicylic acid's use in order to maximize its therapeutic effect and its safety. Moreover, we mention the ongoing clinical trials evaluating the role of acetylsalicylic acid in prevention of colorectal and other cancers. Keywords: Acetylsalicylic Acid, Aspirin, Cyclooxygenase Inhibitors, Prostaglandin Endoperoxide Synthase Inhibitors, Platelet Aggregation Inhibitors, Antithrombotic Agents