The role of arachidonic acid metabolites in cardiovascular homeostasis. Biochemical, histological and clinical cardiovascular effects of non-steroidal anti-inflammatory drugs and their interactions with cardiovascular drugs

Abstract

Derivatives of arachidonic acid may be involved in atherosclerosis and its clinical complications. There is much interest in pharmacologically manipulating the arachidonic acid cascade as a means of preventing cardiovascular disease. The development of atherosclerosis has been intensively studied and the consequences of cardiovascular or cerebrovascular vessel occlusion are too familiar. Many factors are probably involved, but the role of plasma lipoproteins and the interactions between various constituents of blood and blood vessel walls have received particular attention. The risk of cardiovascular disease associated with high plasma concentrations of the low density lipoproteins and the possible protective effects of high density lipoproteins have been well documented. Much is now known about lipoprotein biochemistry, and the importance of controlling the quantity and quality of dietary lipids has been demonstrated in epidemiological studies. In studies of patients with transient ischaemic attacks, aspirin reduced the risk of stroke and death in males, although these benefits were not as convincingly demonstrated in women. The majority of patients were given aspirin 1300 mg daily, but the optimum dosage was not properly evaluated. Administering aspirin in combination with another antiplatelet drug did not appear to offer any therapeutic advantage in these patients. Aspirin showed a positive, but non-significant trend towards reduced numbers of cardiac events, non-fatal infarcts and total mortality in patients who had experienced at least one myocardial infarction. In contrast, statistically significant beneficial effects were recorded when patients with unstable angina were administered aspirin. The risks of myocardial infarction or coronary death were reduced by 51% in 2 large studies.(ABSTRACT TRUNCATED AT 250 WORDS)