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      Less Benefit from Warfarin in Diabetics after Myocardial Infarction?

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          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.

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          Most cited references 11

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          Warfarin, aspirin, or both after myocardial infarction.

          The role of antithrombotic therapy in secondary prevention after myocardial infarction is well established. Although the available literature suggests that warfarin is superior to aspirin, aspirin is currently the more widely used drug. We studied the efficacy and safety of warfarin, aspirin, or both after myocardial infarction. In a randomized, multicenter trial in 3630 patients, 1216 received warfarin (in a dose intended to achieve an international normalized ratio [INR] of 2.8 to 4.2), 1206 received aspirin (160 mg daily), and 1208 received aspirin (75 mg daily) combined with warfarin (in a dose intended to achieve an INR of 2.0 to 2.5). The mean duration of observation was four years. The primary outcome, a composite of death, nonfatal reinfarction, or thromboembolic cerebral stroke, occurred in 241 of 1206 patients receiving aspirin (20.0 percent), 203 of 1216 receiving warfarin (16.7 percent; rate ratio as compared with aspirin, 0.81; 95 percent confidence interval, 0.69 to 0.95; P=0.03), and 181 of 1208 receiving warfarin and aspirin (15.0 percent; rate ratio as compared with aspirin, 0.71; 95 percent confidence interval, 0.60 to 0.83; P=0.001). The difference between the two groups receiving warfarin was not statistically significant. Episodes of major, nonfatal bleeding were observed in 0.62 percent of patients per treatment-year in both groups receiving warfarin and in 0.17 percent of patients receiving aspirin (P<0.001). Warfarin, in combination with aspirin or given alone, was superior to aspirin alone in reducing the incidence of composite events after an acute myocardial infarction but was associated with a higher risk of bleeding. Copyright 2002 Massachusetts Medical Society
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            Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial.

            Antiplatelet treatment with aspirin and oral anticoagulants reduces recurrence of ischaemic events after myocardial infarction. We aimed to investigate which of these drugs is more effective in the long term after acute coronary events, and whether the combination of aspirin and oral anticoagulants offers greater benefit than either of these agents alone, without excessive risk of bleeding. In a randomised open-label trial in 53 sites, we randomly assigned 999 patients to low-dose aspirin, high-intensity oral anticoagulation, or combined low-dose aspirin and moderate intensity oral anticoagulation. Patients were followed up for a maximum of 26 months. The primary composite endpoint was first occurrence of myocardial infarction, stroke, or death. The primary endpoint was reached in 31 (9%) of 336 patients on aspirin, in 17 (5%) of 325 on anticoagulants (hazard ratio 0.55 [95% CI 0.30-1.00], p=0.0479), and in 16 (5%) of 332 on combination therapy (0.50 [0.27-0.92], p=0.03). Major bleeding was recorded in three (1%) patients on aspirin, three (1%) on anticoagulants (1.03 [0.21-5.08], p=1.0), and seven (2%) on combination therapy (2.35 [0.61-9.10], p=0.2). Frequency of minor bleeding was 5%, 8% (1.68 [0.92-3.07], p=0.20), and 15% (3.13 [1.82-5.37], p=<0.0001), in the three groups, respectively. 164 patients permanently discontinued the study drug. Analyses were done by intention to treat. In patients recently admitted with acute coronary events, treatment with high-intensity oral anticoagulants or aspirin with medium-intensity oral anticoagulants was more effective than aspirin on its own in reduction of subsequent cardiovascular events and death.
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              Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level, and relative body weight in normal and obese subjects.

              This study was undertaken to obtain further information on the mechanism by which blood fibrinolytic activity, a balance between plasminogen activators and inhibitors, is lowered in obese subjects. Fasting blood samples were collected from 35 subjects, aged 15 to 45 years, with normal glucose tolerance and a Body Mass Index (BMI) varying widely between 16 and 45 (normal, 19 to 25). Euglobulin Fibrinolytic Activity (EFA) did not correlate with the level of tissue type plasminogen activator (t-PA) related antigen but exhibited a negative correlation with the level of PA inhibitor (r = -.609, P less than 0.01). EFA was negatively and PA inhibitor positively correlated with both BMI (r = -.381, P less than 0.02 and .664, P less than 0.01, respectively) and plasma insulin level (r = .410, P less than 0.02 and .521, P less than 0.01, respectively). Stepwise analysis showed that these correlations were independent. As expected, plasma insulin was correlated with BMI (r = .512, P less than 0.01) and triglyceride level (r = .38, P less than 0.02), total cholesterol with age (r = .379, P less than 0.02). Ten obese subjects were submitted to a 24-hour fast. While body weight did not change appreciably, plasma insulin decreased from 22.3 +/- 2.2 to 16.3 +/- 1.1 microU/ml, EFA increased from 3.6 +/- .8 to 4.9 +/- .67 mm, and PA inhibitor decreased from 4.52 +/- .76 to 3.44 +/- .63 IU/mL. All these differences were significant. T-PA-related antigen did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

                Author and article information

                S. Karger AG
                September 2008
                25 April 2008
                : 111
                : 3
                : 161-166
                aDepartment of Internal Medicine, Asker and Baerum Hospital, Rud, bDepartment of Cardiology, Akershus University Hospital, Lørenskog, and cDepartment of Cardiology and dCenter for Clinical Research, Ulleval University Hospital, Oslo, Norway
                121598 Cardiology 2008;111:161–166
                © 2008 S. Karger AG, Basel

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                Figures: 1, Tables: 4, References: 21, Pages: 6
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