Objectives: To examine the impact of prognostic factors on the outcome of treatment with warfarin or aspirin after acute myocardial infarction. Methods: Patients from the Warfarin Aspirin Re-Infarction Study, assigned to treatment with warfarin (n = 1,216) or aspirin (n = 1,206) after myocardial infarction, were stratified according to important prognostic factors. Survival from the composite endpoint of death, myocardial infarction and thromboembolic stroke was estimated within each stratum by odds ratios (OR). The effect of therapy was then tested for heterogeneity across the two groups. Unadjusted analyses were complemented with regression analyses. Results: In diabetics the OR was 1.54 (95% CI 0.80–2.94) compared to 0.75 (95% CI 0.60–0.93) in nondiabetic patients. The latter difference was statistically significant when testing for heterogeneity, suggesting effect modification of warfarin by diabetes. After adjusting for confounders, diabetic patients who received warfarin had a 56% excess risk of an endpoint as compared with those receiving aspirin. By contrast, nondiabetic patients on warfarin had a 22% lower risk of an endpoint than those allocated to aspirin. Conclusions: The present data suggest less benefit from warfarin as compared to aspirin in diabetics. The mechanisms behind this remain in question.

Smith P, Arnesen H, Holme I: The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med 1990;323:147–152.
Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis (ASPECT) Research Group: Effect of long-term oral anticoagulant treatment on mortality and cardiovascular morbidity after myocardial infarction. Lancet 1994;343:499–503.
Anand SS, Yusuf S: Oral anticoagulant therapy in patients with coronary artery disease: a meta-analysis. JAMA 1999;282:2058–2067.
van Es RF, Jonker JJ, Verheugt FW, Deckers JW, Grobbee DE: Antithrombotics in the Secondary Prevention of Events in Coronary Thrombosis-2 (ASPECT-2) Research Group. Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet 2002;360:109–113.
Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H: Warfarin, aspirin or both after myocardial infarction. N Engl J Med 2002;347:969–974.
Loeliger EA: The optimal therapeutic range in oral anticoagulation. History and proposal. Thromb Haemost 1979;42:1141–1152.
Kirkwood TB: Calibration of reference thromboplastins and standardisation of the prothrombin time ratio. Thromb Haemost 1983;49:238–244.
Smith P, Arnesen H, Abdelnoor M: Effects of long-term anticoagulant therapy in subgroups after acute myocardial infarction. Arch Intern Med 1992;152:993–997.
Nomenclature and criteria for diagnosis of ischemic heart disease: report of the Joint International Society and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature. Circulation 1979;59:607–609.
Breslow NE, Day DN: Classical methods of analysis of grouped data; in Breslow NE, Day DN (eds): Statistical Methods in Cancer Research. The Analysis of Case-Control Studies. Lyon, World Health Organization, International Agency for Research on Cancer, 1980, pp 122–159.
Byar DP: Assessing apparent treatment – covariate interactions in randomized clinical trials. Stat Med 1985;4:255–263.
van Bergen PF, Deckers JW, Jonker JJ, van Domburg RT, Azar AJ, Hofman A: Efficacy of long-term anticoagulant treatment in subgroups of patients after myocardial infarction. Br Heart J 1995;74:117–121.
Johnson SG, Witt DM, Delate T, Sadler MA: An examination of the association between therapeutic anticoagulation control and glycemic control for patients with diabetes on oral anticoagulation therapy. J Thromb Thrombolysis 2005;19:209–212.
Vague P, Juhan-Vague I, Aillaud MF, Badier C, Viard R, Alessi MC, Collen D: Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level and relative body weight in normal and obese subjects. Metabolism 1986;35:250–253.
Wannamethee SG, Lowe GDO, Shaper AG, Rumley A, Lennon L, Whincup PH: Insulin resistance, haemostatic and inflammatory markers and coronary heart disease risk factors in type 2 diabetic men with and without coronary heart disease. Diabetologia 2004;47:1557–1565.
Taube J, McWilliam N, Luddington R, Byrne CD, Baglin T: Activated protein C resistance, effect of platelet activation, platelet derived microparticles, and atherogenic lipoproteins. Blood 1999;93:3792–3797.
Fattah MA, Shaheen MH, Mahfouz MH: Disturbances in haemostasis in diabetes mellitus. Dis Markers 2004;19:251–258.
Mustand JF, Packham MA: Platelets and diabetes mellitus. N Engl J Med 1984;311:665–667.
Lupu C, Calb M, Ionescu M, Lupu F: Enhanced prothrombin and intrinsic factor X activation on blood platelets from diabetic patients. Thromb Haemost 1993;70:579–583.
Cohen Z, Gonzales RF, Davis-Gorman GF, Copeland Jack G, McDonagh PF: Thrombin activity and platelet microparticle formation are increased in type 2 diabetic patients: a potential correlation with caspase activation. Thromb Res 2002;107:217–221.
Halfon S, Malinowski J, Sinha U: Effect of anticoagulants and antiplatelet agents on platelet-mediated thrombin generation. Blood Coagul Fibrinolysis 2002;13:715–724.
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