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.


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.
Brouwer
Marc A
MA
Interuniversity Cardiology Institute of the Netherlands, Nijmegen.
van den Bergh
Paul J P C
PJ
Aengevaeren
Wim R M
WR
Veen
Gerrit
G
Luijten
Hans E
HE
Hertzberger
Don P
DP
van Boven
Ad J
AJ
Vromans
Ralf P J W
RP
Uijen
Gérard J H
GJ
Verheugt
Freek W A
FW
D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D017023:Coronary Angiography; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000517:prevention & control*; D003374:Coumarins / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015912:Thrombolytic Therapy; D016896:Treatment Outcome
D000925:Anticoagulants; D003374:Coumarins; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D006493:Heparin; C030123:coumarin; D001241:Aspirin