Summary
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 1300mg 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. Aspirin may also be of value in maintaining the patency of coronary bypass grafts. When administered in combination with dipyridamole the incidence of graft occlusions after 1 year was 11% compared with 25% in the placebo group.
Similar content being viewed by others
References
Anturan Reinfarction Italian Study. Sulphinpyrazone in postmyocardial infarction. Lancet 1: 237–242, 1982
Anturane Reinfarction Trial Research Group. Sulfinpyrazone in the prevention of sudden death after myocardial infarction. New England Journal of Medicine 302: 250–256, 1980
Aspirin Myocardial Infarction Study Research Group. A randomised controlled trial of aspirin in persons recovered from myocardial infarction. Journal of the American Medical Association 243: 661–669, 1980
Breddin K, Loew D, Lechner K, Überla K, Walter E. Secondary prevention of myocardial infarction. Comparison of acetylsalicylic acid,phenprocoumon and placebo. A multicenter two-year prospective trial. Thrombosis and Haemostasis 41: 225–236, 1979
Bousser MG, Eschwege E, Haguenau M, Lefaucconnier J, Thibult N, et al. ‘AICLA’ controlled trial of aspirin and dipyridamole in the secondary prevention of atherothrombotic cerebral ischaemia. Stroke 14: 5–14, 1983
Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science 232: 34–47, 1986
Brown BG, Cukingnan RA, De Rouen T, Goede LV, Wong M,et al. Improved graft potency in patients treated with platelet-inhibiting therapy after coronary bypass surgery. Circulation 72 (Suppl. 1): 138–146, 1985
Cairns J, Gent M, Singer J, Finnie K, Froggatt G, et al. A study of aspirin (ASA) and/or sulphinpyrazone (S) in unstable angina (UA). Circulation 70: 11–415, 1984
Canadian Cooperative Study Group. A randomized trial of aspirin and sulfinpyrazone in threatened stroke. New England Journal of Medicine 299: 53–59, 1978
Castelli WP, Doyle JT, Gordon T, Harnes C, Hjortland MC, et al. HDL cholesterol and other lipids in coronary heart disease. The Co-operative Lipoprotein Phenotyping Study. Circulation 55: 767–772, 1977
Chesebro JH, Clements IP, Fuster V, Elveback LR, Smith HC, et al. A platelet-inhibitor-drug trial in coronary-artery bypass operations. New England Journal of Medicine 307: 73–78, 1982
Coronary Drug Project Research Group. Aspirin in coronary heart disease. Journal of Chronic Diseases 29: 625–642, 1976
Elwood PC, Sweetman PM. Aspirin and secondary mortality after myocardial infarction. Lancet 2: 1313–1315, 1979
Elwood PC, Cochrane AL, Burr ML, Sweetnam PM, Williams G, et al. A randomized controlled trial of acetyl salicylic acid in the secondary prevention of mortality from myocardial infarction. British Medical Journal I: 436–440, 1974
Fields WS, Lemak NA, Frankowski RF, Hardy RJ. Controlled trial of aspirin in cerebral ischemia. Stroke 8: 301–316, 1977
Fuster V, Chesebro JH. Role of platelets and platelet inhibitors in aortocoronary artery vein-graft disease. Circulation 73 (Suppl. 2): 227–232, 1986
Gryglewski RJ, Dembinska-Kiec A, Zmuda A, et al. Prostacyclin and thromboxane A2 biosynthesis capacities of heart,arteries, and platelets at various stages of experimental atherosclerosis in rabbits. Atherosclerosis, 31: 385–394, 1978
Harker LA. Clinical trials evaluating platelet-modifying drugs in patients with atherosclerotic,cardiovascular disease and thrombosis. Circulation 73 (Suppl. 2): 206–223, 1986
Heldin C-H, Wasteson A, Westermark B. Platelet-derived growth factor. Molecular and Cellular Endocrinology 39: 169–187, 1985
Herbert PN, Assman G, Gotto Jr A, Fredrickson DS. Familial lipoprotein deficiency. In Stanbury et al. (Eds) The metabolic basis of inherited disease, 5th ed., pp. 589–621, McGraw-Hill, New York, 1983
Lewis HD, Davis JW, Archibald DG, Steinke WE, Smitherman TC, et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. New England Journal of Medicine 309: 396–403, 1983
Lipid Research Clinics Program. The lipid research clinics coronary primary prevention trial results. Journal of the American Medical Association 251 (Parts I-II): 351–374, 1984
Moore S. Injury mechanisms in atherogenesis. In Moore (Ed) Vascular Injury and Atherosclerosis. pp. 131–148, Marcel Dekker Inc. New York,1981
NIH Consensus Development Conference Statement. Lowering blood cholesterol to prevent heart disease. Arteriosclerosis 5: 404–412, 1985
Persantine-Aspirin Reinfarction Study Research Group. Persantine and aspirin in coronary heart disease. Circulation 62: 449–461, 1980
Persantine Aspirin Trial in Cerebral Ischaemia. Part II: Endpoint results. The American-Canadian Co-operative Study Group. Stroke 16 (Suppl. 3): 406–415, 1985
Rajah SM, Salter MC, Donaldson DR, Subba Rao R, Boyle RM, et al. Acetylsalicylic acid and dipyridamole improve the early patency of aorta-coronary bypass grafts. A double-blind placebo-controlled randomized trial. Journal of Thoracic Cardiovascular Surgery 90 (Suppl. 3): 373–377, 1985
Ross R. The pathogenesis of atherosclerosis. New England Journal of Medicine 314: 488–500, 1986
Ross R, Glomset JA. The pathogenesis of atherosclerosis. New England Journal of Medicine 295 (Part I): 369–377, 1976
Sigurdsson G, Nicoll A, Lewis B. Conversion of very low density lipoprotein to low density lipoprotein. A metabolic study of apolipoprotein B kinetics in human subjects. Journal of Clinical Investigation 56: 1481–1490, 1975
Weiss HJ. Platelets: Pathophysiology and Antiplatelet Drug Therapy. In Weiss (Ed), AR Liss, New York, 1982
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Goodman, D.S. The Role of Arachidonic Acid Metabolites in Cardiovascular Homeostasis. Drugs 33 (Suppl 1), 47–55 (1987). https://doi.org/10.2165/00003495-198700331-00008
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-198700331-00008