October 1, 1994Circulation
Hirudin in acute myocardial infarction. Safety report from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9A Trial.
Why the study?
Does intravenous hirudin compared to heparin improve safety (reduce major hemorrhage or anaphylaxis) in patients with acute myocardial infarction receiving thrombolysis and aspirin?
Population
757 patients with acute myocardial infarction
Comparison
Intravenous hirudin as adjunctive therapy to… vs Heparin as adjunctive therapy to thrombolysis…
Design
RCT, Randomized (randomization was suspended after 757 patients)
Authors
Discussion
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Implication
Hirudin increases major nonintracranial bleeding versus heparin in thrombolyzed AMI; challenges phase II safety estimates and prompted subsequent dose reductions.
Key Points
- This trial aimed to compare the efficacy and safety of hirudin with heparin as treatment for acute myocardial infarction.
- Enrolled 757 patients in a randomized trial comparing intravenous hirudin and modified heparin therapy.
- Hirudin administered as a 0.6 mg/kg bolus followed by a 96-hour infusion of 0.2 mg/kg per hour.
- Heparin administered with initial bolus and infusion based on patient weight with aPTT aimed at 60 to 90 seconds.
- Major spontaneous hemorrhage occurred in 7.0% of hirudin patients versus 3.0% in heparin patients (P = .02).
- Incident of intracranial hemorrhage was 1.7% with hirudin and 1.9% with heparin (P = NS).
- Higher aPTT levels correlated with increased risk of major hemorrhage in both groups.
Structured PICO
Does intravenous hirudin compared to heparin improve safety (reduce major hemorrhage or anaphylaxis) in patients with acute myocardial infarction receiving thrombolysis and aspirin?
P
Population
757 patients with acute myocardial infarction
I
Intervention
Intravenous hirudin (bolus 0.6 mg/kg followed by a fixed-dose 96-hour infusion of 0.2 mg/kg per hour) as adjunctive therapy to thrombolysis and aspirin
C
Comparator
Heparin (modified weight-adjusted regimen: 5000-U bolus and infusion of 1000 U/h for patients < 80 kg or 1300 U/h for patients >= 80 kg, titrated to a target aPTT of 60 to 90 seconds) as adjunctive therapy to thrombolysis and aspirin
O
Outcome
Occurrence of major hemorrhage or anaphylaxissafety
The TIMI 9A trial demonstrated that the selected doses of hirudin and heparin as adjuncts to thrombolysis in AMI caused unacceptably high rates of major hemorrhage, necessitating dose reductions and strict aPTT monitoring in subsequent trials.
Cite This Study
Elliott M. Antman (1994) studied this question.