Aspirin plus coumarin versus aspirin alone in the prevention of reocclusion after fibrinolysis for acute myocardial infarction: results of the Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis (APRICOT)-2 Trial.

BACKGROUND: Despite the use of aspirin, reocclusion of the infarct-related artery occurs in approximately 30% of patients within the first year after successful fibrinolysis, with impaired clinical outcome. This study sought to assess the impact of a prolonged anticoagulation regimen as adjunctive to aspirin in the prevention of reocclusion and recurrent ischemic events after fibrinolysis for ST-elevation myocardial infarction. METHODS AND RESULTS: At coronary angiography <48 hours after fibrinolytic therapy, 308 patients receiving aspirin and intravenous heparin had a patent infarct-related artery (Thrombolysis In Myocardial Infarction [TIMI] grade 3 flow). They were randomly assigned to standard heparinization and continuation of aspirin alone or to a 3-month combination of aspirin with moderate-intensity coumarin, including continued heparinization until a target international normalized ratio (INR) of 2.0 to 3.0. Angiographic and clinical follow-up were assessed at 3 months. Median INR was 2.6 (25 to 75th percentiles 2.1 to 3.1). Reocclusion (< or =TIMI grade 2 flow) was observed in 15% of patients receiving aspirin and coumarin compared with 28% in those receiving aspirin alone (relative risk [RR], 0.55; 95% CI 0.33 to 0.90; P<0.02). TIMI grade 0 to 1 flow rates were 9% and 20%, respectively (RR, 0.46; 95% CI, 0.24 to 0.89; P<0.02). Survival rates free from reinfarction and revascularization were 86% and 66%, respectively (P<0.01). Bleeding (TIMI major and minor) was infrequent: 5% versus 3% (P=NS). CONCLUSIONS: As adjunctive to aspirin, a 3-month-regimen of moderate-intensity coumarin, including heparinization until the target INR is reached, markedly reduces reocclusion and recurrent events after successful fibrinolysis. This conceptual study provides a mechanistic rationale to further investigate the role of prolonged anticoagulation after fibrinolytic therapy.

Prehospital thrombolysis with reteplase: the Nijmegen/Rotterdam study.

OBJECTIVE: The objective of this observational study was to assess time from electrocardiogram diagnosis to treatment and time from pain onset to treatment with double bolus reteplase compared to current therapy with streptokinase or bolus anistreplase in 2 cities (Rotterdam and Nijmegen) in the Netherlands, where prehospital thrombolysis is an established way of treatment of acute myocardial infarction. METHODS: Prehospital thrombolysis is performed using electrocardiogram diagnosis by the ambulance service as well as bolus anistreplase for treatment in Nijmegen, and streptokinase infusion in Rotterdam. Reteplase or anistreplase/streptokinase was assigned open label to patients according to order of presentation on a 1-to-1 basis. All patients were treated with nitrates sublingually and aspirin orally. Time intervals were recorded by the ambulance staff. RESULTS: In total, 250 patients were treated between April 1, 1999 and August 1, 2000. Reteplase was used in 120 patients and anistreplase/streptokinase in 130 patients. Using double bolus reteplase resulted in a significantly shorter time to treatment: a median of 81 minutes compared to a median of 104 minutes with the established therapy (P <.0001). There were no differences in mortality, aborted myocardial infarction, hemorrhagic stroke or the need for rescue angioplasty between the groups. CONCLUSION: In prehospital thrombolysis, double bolus reteplase is associated with a shorter time to treatment than bolus anistreplase or infusion of streptokinase.

Prehospital versus hospital fibrinolytic therapy using automated versus cardiologist electrocardiographic diagnosis of myocardial infarction: abortion of myocardial infarction and unjustified fibrinolytic therapy.

BACKGROUND: This study investigated the incidence of abortion of myocardial infarction and of unjustified fibrinolysis by using automated versus cardiologist-assisted diagnosis of acute ST-elevation myocardial infarction. The results of prehospital diagnosis and treatment (2 cities in the Netherlands) were compared with those of inhospital treatment. Unjustified fibrinolysis must be differentiated from justified thrombolysis resulting in aborted myocardial infarction. Both have the absence of a significant rise in cardiac enzymes in common. In aborted myocardial infarction, this is a result of timely reperfusion; in unjustified thrombolysis, this is the result of an incorrect diagnosis. METHODS: In the city of Rotterdam, 118 patients were treated before hospitalization for myocardial infarction, diagnosed through the use of a mobile computer electrocardiogram; in the city of Nijmegen, 132 patients were treated before hospitalization with the use of transtelephonic transmission of the electrocardiogram to the coronary care unit and judged by a cardiologist. Their data were compared with those of 269 patients treated inhospital in the city of Arnhem, using the same electrocardiographic criteria. Abortion of myocardial infarction was diagnosed as the absence of a significant rise in cardiac enzymes and the presence of resolution of chest pain and 50% of ST-segment deviation within 2 hours after onset of therapy. Lacking these, the diagnosis of unjustified fibrinolytic therapy was made. RESULTS: Unjustified treatment occurred in 8 (3.2%) prehospital-treated patients (4 in Rotterdam and 4 in Nijmegen). Of the inhospital-treated patients in Arnhem, 5 (1.9%) were treated unjustifiably (P =.49). Aborted myocardial infarction occurred in 15.3% and 18.2% in Rotterdam and Nijmegen, respectively, against 4.5% in inhospital treatment in Arnhem (P <.001). CONCLUSIONS: Abortion of myocardial infarction is associated with prehospital thrombolysis. Unjustified fibrinolysis for acute myocardial infarction occurs in prehospital fibrinolysis as frequently as in the inhospital setting. The use of different electrocardiographic methods for diagnosing acute myocardial infarction does not appear to make any difference.