Equal Antiplatelet Effects of Aspirin 50 or 324 mg/Day in Patients After Acute Myocardial Infarction

Summary

This study explores the effects on some hematological parameters of a low-dose aspirin regimen (50 mg/day) versus a conventional aspirin treatment with reported antithrombotic efficacy (324 mg/day), in patients with acute myocardial infarction. Fifteen patients were randomized into 3 equal groups receiving 50 mg or 324 mg aspirin or placebo, daily for 21 days. Compared with placebo, bleeding time was significantly and similarly prolonged with both aspirin doses (+ 71 ± 22% and + 69 ± 20%, mean ± S.D.). Aspirin 50 mg/day suppressed arachidonate-induced platelet aggregation and secondary phase aggregation after ADP and adrenaline. Collagen aggregation was inhibited by 44 ± 15%. In no case were differences in the antiplatelet effects of the two doses observed. The effects of 50 mg/day persisted without attenuation during the observation period. Platelet thromboxane B₂ generation during arachidonate-induced aggregation was inhibited by 95 ± 2 and 99 ± 1% compared to placebo group after 50 and 324 mg/day, respectively (P between doses <0.05). No change was observed with any treatment in coagulation time, prothrombin time or plasma thromboplastin time. Thus, in patients with acute myocardial infarction, the antiplatelet effects of aspirin 50 mg/day are stable over time and superimposable on those of 324 mg/day. The antithrombotic efficacy of aspirin 50 mg/day remains to be tested clinically.

Keywords

Aspirin - Myocardial infarction - Thromboxane - Prostacyclin

• References

• 1 Roth CJ, Majerus PW. The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particular fraction protein. J Clin Invest 1975; 56: 624-632
• 2 Flower RJ, Moncada S, Vane JR. Analgesic-antipyretics and antiinflammatory agents. In: The Pharmacological Basis of Therapeutics. Goodman-Gilman A, Goodman S, Gilman A. (eds.) MacMillan Publishing Co.; New York: 1980. 682 728
• 3 FitzGerald GA, Pedersen AK, Patrono C. Analysis of prostacyclin and thromboxane biosynthesis in cardiovascular disease. Circulation 1983; 67: 1174-1177
• 4 Patrono C, Ciabattoni G, Pinca E, Pugliese F, Castrucci G, De Salvo A, Satta MA, Peskar BA. Low-dose aspirin and inhibition of thromboxane B₂ production in healthy subjects. Thromb Res 1980; 17: 317-327
• 5 FitzGerald GA, Oates JA, Hawiger J, Maas RL, Roberts II LJ, Lawson JA, Brash AR. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man. J Clin Invest 1983; 71: 676-688
• 6 Patrignani P, Filabozzi P, Patrono C. Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects. J Clin Invest 1982; 69: 1366-1372
• 7 De Caterina R, Giannessi D, Bernini W, Gazzetti P, Michelassi C, L’Abbate A, Donato L, Patrignani P, Filabozzi P, Patrono C. Low-dose aspirin in patients recovering from myocardial infarction: Evidence for a selective inhibition of thromboxane-related platelet function. Eur Heart J. (in press)
• 8 Majerus PW. Arachidonate metabolism in vascular disorder. J Clin Invest 1983; 72: 1521-1525
• 9 Marcus AJ. Aspirin as an antithrombotic medication. N Engl J Med 1983; 309: 1515-1516
• 10 Patrono C, Ciabattoni G, Patrignani P, Pugliese F, Filabozzi P, Catella F, Davì G, Forni L. Clinical pharmacology of platelet cyclooxygenase inhibition. Circulation. 1985 (in press)
• 11 Lewis DL, Davis JW, Archibald DC, Steinke WE, Smitherman TC, Doherty III JE, Schnaper HW, LeWinter MN, Linares E, Pouget JM, Sabharwal SC, Chesler E, DeMots H. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study. N Engl J Med 1983; 309: 396-403
• 12 Horan LG, Flowers NC. Electrocardiography and vectorcardiography. In: Heart Disease. Braunwald E. (ed.). W. B. Saunders Co.; Philadelphia, London, Toronto: 1980: 235
• 13 Mielke Jr Ch. Template bleeding time: techniques. In: Platelet function testing. Day HJ, Holmsetr H, Zucker MD. (ed). Proceedings DHEW Publication; Bethesda: 1978: 78-87
• 14 Giannessi D, De Caterina R, Gazzetti P, Bernini W, Masini S, Zucchelli GC. Methodological assessment and applications of a radioimmunoassay for thromboxane (TX) B₂ to measurement of TXB₂ release by platelets. J Nucl Med Allied Sci 1982; 26: 25-33
• 15 Zar JH. Biostatistical analysis. Englewood Cliffs. Prentice-Hall, Inc.. (2nd edition)
• 16 Harter HR, Burch JW, Majerus PW, Stanford N, Delmez JA, Anderson CB, Weerts CA. Prevention of thrombosis in patients on hemodialysis by low-dose aspirin. N Engl J Med 1979; 301: 577-579
• 17 Lorenz RL, Schacky CV, Weber M, Meister W, Kotzur J, Reichardt B, Theisen K, Weber PC. Improved aortocoronary bypass patency by low-dose aspirin (100 mg daily). Lancet 1984; 01: 1261-1264
• 18 Buchanan MR, Rischke JA, Hirsh J. Aspirin inhibitis platelet function independent of the acetylation of cyclooxygenase. Thromb Res 1982; 25: 363-373
• 19 Weksler BB, Kent JL, Rudolph D, Scherer PB, Levy DE. Effects of low dose aspirin on platelet function in patients with recent cerebral ischemia. Stroke 1985; 16: 05-09
• 20 McKenna R, Galante J, Bachmann F, Wallace DL, Kaushal SP, Meredith P. Prevention of venous thromboembolism after total knee replacement by high-dose aspirin or intermittent calf and thigh compression. Br Med J 1980; 280: 514-517
• 21 Hirsch J. Progress review: the relationship between dose of aspirin, side-effects and antithrombotic effectiveness. Stroke 1985; 16: 01-04
• 22 Nuñez L, Gil Aguado M, Larrea JL, Celemìn D, Oliver J. Prevention of thromboembolism using aspirin after mitral valve replacement with porcine bioprosthesis. Ann Thor Surg 1984; 37: 84-87
• 23 Cairns J, Gent M, Singer J, Finnie K, Frogatt G, Holder D, Jablonsky G, Kostuk W, Melendez L, Myers M, Sackett D, Sealey B, Tanser P. (abstr.) A study of aspirin (ASA) and/or sulfinpyrazone (S) in unstable angina (UA). Circulation 1984; 70 (Suppl. 02) 415 (Abstr)
• 24 FitzGerald GA, Smith B, Pedersen AK, Brash AR. Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation. N Engl J Med 1984; 310: 1065-1068
• 25 Sinziger H, O’Grady J, Fitscha P, Kaliman J. Extremely-low-dose aspirin (one milligram per day) renders human platelets more sensitive to anti-aggregatory prostaglandins. N Engl J Med 1984; 311: 1052
• 26 The Canadian Cooperative Study Group. A randomized trial of aspirin and sulfinpyrazone in threatened stroke. N Engl J Med 1978; 299: 53-59
• 27 Rajah SM, Penny A, Kester R. Aspirin and bleeding time. Lancet 1978; 01: 1104
• 28 O’Grady J, Moncada S. Aspirin: a paradoxical effect on bleeding time. Lancet 1978; 01: 780
• 29 Pedersen AK, FitzGerald GA. Dose-related kinetics of aspirin: presystemic acetylation of platelet cyclooxygenase. N Engl J Med 1984; 311: 1211-1214