Less benefit from warfarin in diabetics after myocardial infarction?

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.

Oral anticoagulation after myocardial infarction.

In the present review, the role of oral anticoagulants (OAC) in the secondary prevention after myocardial infarction (MI) is discussed in the light of the results from large randomized clinical trials. In particular, recently published trials and meta-analyses including the combination of OAC and low-dose aspirin are presented. The data show a superiority of OAC over aspirin in reducing thromboembolic events after MI. The combined therapy with OAC and low-dose aspirin has been shown to be particularly beneficial, provided the intensity of anticoagulation is adequate (International Normalized Ratio [INR] 2.0-2.5). With this combined therapy, the risk of serious and fatal bleeding complications equals that with OAC alone. Preassumptions for the efficacy and safety of this treatment modality are good patient compliance and strict INR control.

Occult bleeding in three different antithrombotic regimes after myocardial infarction. A WARIS-II subgroup analysis.

INTRODUCTION: Warfarin, aspirin, and the combination of these, have all proven to be efficacious in preventing future events after myocardial infarction. The accompanying bleeding tendency is a concern. The aim of the present study was to compare the occurrence of occult bleeding and iron deficiency during these treatment modalities. METHODS: The 267 patients who had survived a myocardial infarction were randomly assigned in the Warfarin Aspirin Reinfarction Study to treatment with aspirin 160 mg/day, or warfarin (INR 2.8-4.2), or aspirin 75 mg/day plus warfarin (INR 2.0-2.5). The patients were screened for the occurrence of occult bleeding in faeces and urine after 3 months. Haemoglobin and iron metabolism parameters were measured at baseline, after 3 months, and at the end of the 4 years follow-up. RESULTS: The number of occult bleeding in faeces was 19 (7.1%) and in urine 29 (10.9%). There were no intergroup differences (p=0.45 and 0.39, respectively). In the occult bleeders, a second test showed 3 (1.1%) positive samples in faeces and 9 (3.4%) in urine. Further investigation revealed 2 cases of malignant disease. Haemoglobin and iron status variables were all within normal limits after 3 months and after 4 years in all treatment groups. CONCLUSIONS: Long-term treatment with aspirin, warfarin, or both, in the present doses and levels of anticoagulation did not lead to anemia or iron deficiency. The occurrence of occult bleeding in faeces and urine was a temporary phenomenon in most patients. Only macroscopic bleedings during these treatment modalities were of clinical importance, and screening for occult bleeding was of limit value.

Influence of aspirin on inflammatory markers in patients after acute myocardial infarction.

The aim of this study was to assess the influence of aspirin on selected inflammatory markers in patients recovering from acute myocardial infarction (AMI). Patients participating in the Warfarin Aspirin Re-Infarction Study-II were randomized to either aspirin 160 mg/day or aspirin 75 mg/day + warfarin, or warfarin alone after AMI. After AMI, aspirin 160 mg/day was associated with significantly lower levels of high-sensitivity C-reactive protein and tumor necrosis factor-alpha than warfarin alone over 4 years. However, the same levels were not predictors for clinical end points.

Warfarin, aspirin, or both after myocardial infarction.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Aspirin non-responsiveness as measured by PFA-100 in patients with coronary artery disease.

INTRODUCTION: The purpose of the present study was to study the concept of aspirin resistance or non-responsiveness by investigating the response to long-term aspirin therapy in patients with a former acute myocardial infarction (AMI). MATERIALS AND METHODS: Patients with an AMI (n=202) randomly assigned to aspirin 160 mg/day (n=71), aspirin 75 mg/day and warfarin (INR 2.0-2.5) (n=58) or warfarin (INR 2.8-4.2) (n=73) were evaluated by the PFA-100(R), biochemical variables and clinical events after a mean treatment period of 4 years. RESULTS: The limit for being an aspirin non-responder was defined as the 95th percentile value in the warfarin alone group (196 s) with the epinephrine cartridge. In patients on aspirin alone 25/71 (35%) were non-responders and on the combination 23/58 (40%). With the adenosine diphosphate (ADP) cartridge only minor differences were found. The levels of thromboxane B(2) in both aspirin groups, in responders as well as in non-responders, were extremely low compared to the warfarin alone group. Evaluating both aspirin groups together (n=129), the levels of soluble P-selectin were significantly higher in non-responders as compared to responders (p=0.012). During the observation period of 4 years with limited number of events, there was a tendency for higher event rates in non-responders as compared to responders (36% vs. 24%, p=0.28). CONCLUSIONS: In our evaluation of the PFA-100(R) a considerable number of post-AMI patients seemed to be non-responders to long-term aspirin therapy in doses of 75 and 160 mg/day. Circulating levels of P-selectin were higher in the non-responders. A tendency to higher incidence of clinical events among non-responders was observed.