Why Are Some Individuals Resistant to the Cardioprotective Effects of Aspirin?

Abstract

It has been slightly more than 100 years since the synthesis, development, and commercialization of acetylsalicylic acid, the most widely consumed drug in the world. It is estimated that 35 000 kg are consumed daily in the United States and 6000 kg in the UK.1 Who would have ever thought that this widely consumed drug would achieve significant uses other than as an analgesic, antipyretic, and anti-inflammatory. The first report of a possible antithrombotic effect of aspirin appeared in 1953 in the Mississippi Valley Medical Journal .2 Dr Craven noticed that the patients who took Aspergum had a tendency to bleed more easily. He concluded that aspirin must be thinning the blood and because thrombosis of the coronary arteries led to myocardial infarction, if his patients took aspirin, they might be less prone to experiencing a myocardial infarction. See p 1650 These prescient observations were succeeded by the discovery by numerous investigators that aspirin could significantly decrease platelet function. In 1971, the mechanism by which aspirin inhibited platelet function began to unfold when Smith and Willis3 demonstrated that aspirin inhibited platelet prostaglandin synthesis. It was subsequently shown that aspirin irreversibly acetylated serine-529 close to the active site of the fatty acid cyclooxygenase (COX).4 In the case of the anucleate platelet, the enzyme is rendered inactive for its lifetime. Samuelsson and co-workers5 demonstrated that thromboxane A2 along with prostaglandin H2 were the arachidonic acid metabolites responsible for activation of the platelet. Thromboxane A2 is also a very effective vasoconstrictor and mitogenic substance. After the discovery of thromboxane A2, numerous studies followed that investigated its potential role in thrombotic cardiovascular diseases. Platelet thromboxane A2 synthesis is increased in acute myocardial infarction, unstable angina, thrombolysis therapy, percutaneous transluminal coronary artery angioplasty, and …