ESTEEM Trial
Background: New-onset atrial fibrillation (AF) occurs commonly after acute myocardial infarction (MI) and is associated with a poor prognosis due to stroke or death. The optimal antithrombotic therapy is unknown. The aim of this study was to investigate whether an oral direct thrombin inhibitor, ximelagatran, added to aspirin, reduced the risk of death, myocardial infarction (MI), and stroke in patients who developed AF after their qualifying MI in the efficacy and safety of the oral direct thrombin inhibitor ximelagatran in patients with recent myocardial damage (ESTEEM) trial.
Methods: The ESTEEM trial evaluated 6 months treatment with ximelagatran together with aspirin, compared to aspirin alone, for prevention of ischemic events in 1883 patients randomized within 14 days after an MI. After their qualifying MI, 174 (9%) patients developed AF in hospital. Multivariate hazard ratios for ximelagatran compared with placebo were calculated by presence AF.
Results: Of 101 patients with AF treated with ximelagatran 7 (6.9%) had either death, MI, or stroke, compared with 15 (20.6%) in 73 patients allocated to placebo. Ximelagatran reduced the risk of death, MI, or stroke by 70% (hazard ratio 0.30, 95% CI 0.12-0.74). For the separate outcome events, we found similar, nonsignificant trends. One major bleeding event occurred in each treatment group.
Conclusions: For patients with MI complicated by AF, the combination of aspirin and an oral direct thrombin inhibitor seems beneficial. The high risk for death, MI, and stroke in this population and the increasing use of percutaneous interventions in MI patients may suggest a combination of long-term antiplatelet and anticoagulant therapy. Randomized clinical trials are warranted.
The mainstay of antithrombotic therapy for patients after an acute myocardial infarction (MI) is aspirin, which reduces the relative risk of recurrent MI, stroke, or vascular death by about 25%. Additional treatment with clopidogrel has been shown beneficial in patients with non—ST-elevation MI and ST-elevation MI and in patients treated with percutaneous coronary intervention (PCI). Several recent studies have also shown that anticoagulation with vitamin K antagonists (VKA) reduces the risk of mortality, reinfarction, and stroke after an MI. On the other hand, bleeding rates increase with an increasing intensity of anticoagulation. The current European MI guidelines do not recommend antithrombotic treatment with VKA in patients after MI, whereas the American guidelines are inconsistent. Consequently, use of VKA is low in this population.
Atrial fibrillation (AF) is a common arrhythmia after MI, with an incidence between 5% and 15%. These patients have a poor prognosis compared with those without AF after MI because of an increased risk for stroke and death. Vitamin K antagonists can reduce the risk of stroke by almost two thirds in patients with AF. However, in the population with MI and concomitant AF, no randomized controlled trials comparing various antithrombotic options are available, and thus, antithrombotic treatment strategies vary across the globe.
A recent observational cohort study from the Register of Information and Knowledge about Swedish Heart intensive care Admissions (RIKS-HIA) revealed that 30% of the patients with MI and AF was treated with oral anticoagulants. The adjusted relative risk for 1-year mortality in this group was 0.73 (95% CI 0.62-0.86) compared with patients treated with platelet inhibitors (absolute risk reduction 7%). The reduction in mortality was mainly caused by a lower rate of ischemic heart disease and stroke.
The aim of this study was to explore whether treatment with an oral direct thrombin inhibitor, ximelagatran, added to aspirin, could be beneficial compared with aspirin alone in patients with an acute MI complicated by AF.
Abstract and Introduction
Abstract
Background: New-onset atrial fibrillation (AF) occurs commonly after acute myocardial infarction (MI) and is associated with a poor prognosis due to stroke or death. The optimal antithrombotic therapy is unknown. The aim of this study was to investigate whether an oral direct thrombin inhibitor, ximelagatran, added to aspirin, reduced the risk of death, myocardial infarction (MI), and stroke in patients who developed AF after their qualifying MI in the efficacy and safety of the oral direct thrombin inhibitor ximelagatran in patients with recent myocardial damage (ESTEEM) trial.
Methods: The ESTEEM trial evaluated 6 months treatment with ximelagatran together with aspirin, compared to aspirin alone, for prevention of ischemic events in 1883 patients randomized within 14 days after an MI. After their qualifying MI, 174 (9%) patients developed AF in hospital. Multivariate hazard ratios for ximelagatran compared with placebo were calculated by presence AF.
Results: Of 101 patients with AF treated with ximelagatran 7 (6.9%) had either death, MI, or stroke, compared with 15 (20.6%) in 73 patients allocated to placebo. Ximelagatran reduced the risk of death, MI, or stroke by 70% (hazard ratio 0.30, 95% CI 0.12-0.74). For the separate outcome events, we found similar, nonsignificant trends. One major bleeding event occurred in each treatment group.
Conclusions: For patients with MI complicated by AF, the combination of aspirin and an oral direct thrombin inhibitor seems beneficial. The high risk for death, MI, and stroke in this population and the increasing use of percutaneous interventions in MI patients may suggest a combination of long-term antiplatelet and anticoagulant therapy. Randomized clinical trials are warranted.
Introduction
The mainstay of antithrombotic therapy for patients after an acute myocardial infarction (MI) is aspirin, which reduces the relative risk of recurrent MI, stroke, or vascular death by about 25%. Additional treatment with clopidogrel has been shown beneficial in patients with non—ST-elevation MI and ST-elevation MI and in patients treated with percutaneous coronary intervention (PCI). Several recent studies have also shown that anticoagulation with vitamin K antagonists (VKA) reduces the risk of mortality, reinfarction, and stroke after an MI. On the other hand, bleeding rates increase with an increasing intensity of anticoagulation. The current European MI guidelines do not recommend antithrombotic treatment with VKA in patients after MI, whereas the American guidelines are inconsistent. Consequently, use of VKA is low in this population.
Atrial fibrillation (AF) is a common arrhythmia after MI, with an incidence between 5% and 15%. These patients have a poor prognosis compared with those without AF after MI because of an increased risk for stroke and death. Vitamin K antagonists can reduce the risk of stroke by almost two thirds in patients with AF. However, in the population with MI and concomitant AF, no randomized controlled trials comparing various antithrombotic options are available, and thus, antithrombotic treatment strategies vary across the globe.
A recent observational cohort study from the Register of Information and Knowledge about Swedish Heart intensive care Admissions (RIKS-HIA) revealed that 30% of the patients with MI and AF was treated with oral anticoagulants. The adjusted relative risk for 1-year mortality in this group was 0.73 (95% CI 0.62-0.86) compared with patients treated with platelet inhibitors (absolute risk reduction 7%). The reduction in mortality was mainly caused by a lower rate of ischemic heart disease and stroke.
The aim of this study was to explore whether treatment with an oral direct thrombin inhibitor, ximelagatran, added to aspirin, could be beneficial compared with aspirin alone in patients with an acute MI complicated by AF.
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