Clinical Trials in Thrombosis: Secondary Prevention of Myocardial Infarction^[*]

Summary

Numerous in vivo and in vitro experiments, investigating the inhibition of platelet aggregation and the prevention of experimentally-induced thrombosis, suggest that anti-platelet drugs, such as aspirin or the combination of aspirin and dipyridamole or sulfinpyrazone, may be effective anti-thrombotic agents in man. Since 1971, seven randomized prospective trials and two case-control studies have been referenced in the literature or are currently being conducted, which evaluate the effects of aspirin, sulfinpyrazone, or dipyridamole in combination with aspirin in the secondary prevention of myocardial infarction. A critical review of these trials indicates a range of evidence from no difference to a favorable trend that antiplatelet drugs may serve as anti-thrombotic agents in man. To date, a definitive answer concerning the therapeutic effects of these drugs in the secondary prevention of coronary heart disease is not available.

^* Presented at the Vth Congress of the International Society on Thrombosis and Haemostasis, Paris, July, 1975.

• Reference

• 1 Blakely J. A, Gent M. 1975. Platelets, Drugs and Longevity in a Geriatric Population. In: Hirsh J. (ed.) Platelets, Drugs, and Thrombosis. S. Karger; Switzerland: 284.
• 2 Boston Collaborative Drug Surveillance Group. 1974; Regular Aspirin Intake and Acute Myocardial Infarction. British Medical Journal 1: 440.
• 3 Breddin K. 1975 Personal Communication.
• 4 Coronary Drug Project Aspirin Study. 1975 Aspirin in Coronary Heart Disease: The Coronary Drug Project Research Group. Submitted to Journal of American Medical Association.
• 5 Danese C. A, Voleti C. D, Weiss H. J. 1971; Protection by Aspirin against Experimentally Induced Thrombosis in Dogs. Thrombosis et Diathesis Haemorrhagica 25: 288.
• 6 Duguid J. B. 1948; Thrombosis as a Factor in the Pathogenesis of Aortic Atherosclerosis. Journal of Pathological Bacteriology 60: 57.
• 7 Elwood P. C, Cochrane A. L, Burr M. L, Sweetname P. M, Williams G, Welsby E, Hughes S. J, Renton R. 1974; A Randomized Controlled Trial of Acetylsalicylic Acid in the Secondary Prevention of Mortality from Myocardial Infarction. British Medical Journal I: 436.
• 8 Elwood P. C. 1975 Personal Communication.
• 9 French J. E. 1971; Atherogenesis and Thrombosis. Sem Hemat 8: 84.
• 10 Gent M. 1975 Personal Communication.
• 11 Genton E, Gent M, Hirsh J, Harker L. A. 1975 Evaluation of Platelet Inhibiting Drugs in the Prevention of Clinical Thrombotic Disease. Submitted to New England Journal of Medicine.
• 12 Haft J. I, Gershengorn K, Kranz P. D, Oestreicher R. 1972; Protection Against Epine-phrine-Induced Myocardial Necrosis by Drugs that Inhibit Platelet Aggregation. American Journal of Cardiology 30: 838.
• 13 Hammond E. C, Garfinkel L. 1975; Aspirin and Coronary Heart Disease: Findings of a Prospective Study. British Medical Journal 2: 269.
• 14 Heikinheimo R, Jarvinen K. 1971; Acetyls alicylic Acid and Arteriosclerotic Thromboembolic Diseases in the Aged. Journal of American Geriatrics Society 19: 403.
• 15 Kaegi A, Pineo G. F, Shimizu A, Trivedi H, Hirsh J, Gent M. 1974; Arteriovenous-Shunt Thrombosis: Prevention by Sulfinpyrazone. New England Journal of Medicine 290: 304.
• 16 Klimt C, Knatterud G. 1975 Personal Communication.
• 17 Krol W, Klimt C. 1975 Personal Communication.
• 18 Krug A, Krug C, Dharamadhach A. 1970; Infarct Size and Enzyme Histochemical Changes in the Rat Heart Following Long Term Treatment with Dipyridamole and Occlusion of the Coronary Arteries. Kreislauf forsch 59: 487.
• 19 Moschos C. B, Lahiri K, Peter A, Jesrani M. U, Regan T. J. 1972; Effects of Aspirin Upon Experimental Coronary and Non-Coronary Thrombosis and Arrhythmia. American Heart Journal 84: 525.
• 20 Moschos C. B, Lahiri K, Lyons M, Weisse A. B, Oldewurtel H. A, Regan T. J. 1973; Relation of Microcirculatory Thrombosis to Thrombus in the Proximal Coronary Artery: Effect of Aspirin, Dipyridamole, and Thrombolysis. American Heart Journal 86: 61.
• 21 Mustard J. F, Packham M. A. 1969. Platelet Function and Myocardial Infarction. In: Bondurant Stuart. (ed.) Research on Acute Myocardial Infarction. American Heart Association Monograph; New York: IV-20.
• 22 O’Brien J. R. 1968; Effects of Salicylates on Human Platelets. Lancet I: 779.
• 23 Peterson J, Zucker M. B. 1970; The Effect of Adenosine Monophosphate. Arcaine and Anti-Inflammatory Agents on Thrombosis and Platelet Function in Rabbits. Thrombosis et Diathesis Haemorrhagica 23: 148.
• 24 Renaud S, Godu J. 1970; Thrombosis Prevention by Acetylsalicylic Axid in Hyperlipemic Rats. Canadian Medical Association Journal 103: 103.
• 25 Weiss H. J, Aledort L. M, Kochwa S. 1968; The Effects of Salicylates on the Hemostatic Properties of Platelets in Man. Journal of Clinical Investigation 47: 2169.
• 26 Wilding R. P, Flute P. T. 1974; Letter: Dipyridamole in Peripheral Upper-Limb Ischemia. Lancet I: 999.