BACKGROUND AND OBJECTIVES: The conjunctive use of intravenous heparin may influence the efficacy of alteplase for coronary thrombolysis in patients with acute myocardial infarction. In this study we examined the relation between the level of intravenous anticoagulation with heparin and sustained coronary artery patency in a subgroup of patients of the European Cooperative Study Group (ECSG) trial. METHODS: In the ECSG trial, patients treated with alteplase and aspirin were randomized to concomitant fixed doses of intravenous heparin (a bolus dose of 5,000 U followed by a continuous infusion of 1,000 U/h or placebo). The current study group comprised 149 of 324 ECSG patients allocated toheparin therapyand 132 of 320 ECSG patients allocated toplacebo administration who had both an interpretable coronary angiogram obtained within 6 days of treatment and sufficient plasma samples to assess the level of anticoagulation. Activated partial thromboplastin times, fibrinogen and D-dimer levels were determined on plasma samples at baseline and at 45 min and 3, 12, 24 and 36 h after the start of alteplase administration. RESULTS: The coronary artery patency rate was higher in patients allocated to heparin therapy than in those allocated to placebo (80% and 71%, respectively, p = 0.05). Patients allocated to heparin were classified into three subgroups: 48 patients (32%) with all activated partial thromboplastin times at least twice their own baseline value (optimal anticoagulation), 40 patients (27%) with the lowest activated partial thromboplastin time at 3, 12, 24 or 36 h between 130% and 200% of the baseline value (suboptimal anticoagulation) and 61 patients with at least one activated partial thromboplastin time less than 130% of baseline (inadequate anticoagulation). In the heparin group, coronary artery patency correlated with the level of anticoagulation: 90%, 80% and 72%, respectively, in patients with optimal, suboptimal and inadequate anticoagulation (p = 0.02, optimal vs. inadequate anticoagulation). Heparin administration was associated with a smaller reduction in fibrinogen and a smaller increase in D-dimer level during and after alteplase administration. No correlation was found between fibrinogen or D-dimer levels and coronary artery patency. No intracerebral hemorrhage occurred in these patients; however, bleeding was more frequent in the subgroup with optimal anticoagulation (p = 0.05). CONCLUSIONS: Intense anticoagulation with intravenous heparin enhances coronary artery patency after alteplase treatment of acute myocardial infarction.
RCT Entities:
BACKGROUND AND OBJECTIVES: The conjunctive use of intravenous heparin may influence the efficacy of alteplase for coronary thrombolysis in patients with acute myocardial infarction. In this study we examined the relation between the level of intravenous anticoagulation with heparin and sustained coronary artery patency in a subgroup of patients of the European Cooperative Study Group (ECSG) trial. METHODS: In the ECSG trial, patients treated with alteplase and aspirin were randomized to concomitant fixed doses of intravenous heparin (a bolus dose of 5,000 U followed by a continuous infusion of 1,000 U/h or placebo). The current study group comprised 149 of 324 ECSG patients allocated to heparin therapy and 132 of 320 ECSG patients allocated to placebo administration who had both an interpretable coronary angiogram obtained within 6 days of treatment and sufficient plasma samples to assess the level of anticoagulation. Activated partial thromboplastin times, fibrinogen and D-dimer levels were determined on plasma samples at baseline and at 45 min and 3, 12, 24 and 36 h after the start of alteplase administration. RESULTS: The coronary artery patency rate was higher in patients allocated to heparin therapy than in those allocated to placebo (80% and 71%, respectively, p = 0.05). Patients allocated to heparin were classified into three subgroups: 48 patients (32%) with all activated partial thromboplastin times at least twice their own baseline value (optimal anticoagulation), 40 patients (27%) with the lowest activated partial thromboplastin time at 3, 12, 24 or 36 h between 130% and 200% of the baseline value (suboptimal anticoagulation) and 61 patients with at least one activated partial thromboplastin time less than 130% of baseline (inadequate anticoagulation). In the heparin group, coronary artery patency correlated with the level of anticoagulation: 90%, 80% and 72%, respectively, in patients with optimal, suboptimal and inadequate anticoagulation (p = 0.02, optimal vs. inadequate anticoagulation). Heparin administration was associated with a smaller reduction in fibrinogen and a smaller increase in D-dimer level during and after alteplase administration. No correlation was found between fibrinogen or D-dimer levels and coronary artery patency. No intracerebral hemorrhage occurred in these patients; however, bleeding was more frequent in the subgroup with optimal anticoagulation (p = 0.05). CONCLUSIONS: Intense anticoagulation with intravenous heparin enhances coronary artery patency after alteplase treatment of acute myocardial infarction.