Abstract | BACKGROUND: METHODS AND RESULTS: Patients were randomized to one of two doses of heparin (n = 50) (target activated partial thromboplastin time, 65 to 90 seconds or 90 to 110 seconds) or one of four doses of r- hirudin (n = 113) (0.05, 0.10, 0.20, or 0.30 mg.kg-1.h-1 by infusion). r- Hirudin induced a dose-dependent decline in plasma FPA. At 24 hours, FPA levels with 0.1- to 0.3-mg.kg-1.h-1 r- hirudin regimens were significantly lower than with 0.05 mg.kg-1.h-1 r- hirudin; levels with 0.1- to 0.2-mg.kg-1.h-1 r- hirudin regimens were lower than with both heparin regimens. Plasma F1.2 did not decline significantly during therapy with heparin or hirudin except at 0.3 mg.kg-1.h-1 hirudin. At 24 hours, they were higher with the 0.05-mg.kg-1.h-1 r- hirudin regimen than with other regimens. For comparable levels of thrombin generation (F1.2 levels), FPA levels were higher in heparin patients than in hirudin patients. For the same FPA values, the corresponding F1.2 values were higher in the hirudin group. CONCLUSIONS: Our findings provide evidence for distinct in vivo effects of the two agents and suggest that r- hirudin is a relatively more potent inhibitor of thrombin action but a less effective inhibitor of thrombin generation than heparin. The lower FPA levels in hirudin patients may reflect its ability to inactivate clot-bound thrombin. The relative clinical efficacies of the two agents need to be defined by clinical trials in progress.
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Authors | A K Rao, L Sun, J H Chesebro, V Fuster, R A Harrington, D Schwartz, P Gallo, D Matos, E J Topol |
Journal | Circulation
(Circulation)
Vol. 94
Issue 10
Pg. 2389-95
(Nov 15 1996)
ISSN: 0009-7322 [Print] United States |
PMID | 8921778
(Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Fibrinolytic Agents
- Hirudins
- Peptide Fragments
- Recombinant Proteins
- antithrombin III-protease complex
- prothrombin fragment 1.2
- Fibrinopeptide A
- Antithrombin III
- Prothrombin
- Heparin
- Peptide Hydrolases
- desirudin
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Topics |
- Angina, Unstable
(blood, diagnostic imaging, drug therapy)
- Antithrombin III
(analysis)
- Coronary Angiography
- Fibrinolytic Agents
(therapeutic use)
- Fibrinopeptide A
(analysis)
- Heparin
(therapeutic use)
- Hirudin Therapy
- Hirudins
(analogs & derivatives)
- Humans
- Partial Thromboplastin Time
- Peptide Fragments
(analysis)
- Peptide Hydrolases
(analysis)
- Prothrombin
(analysis)
- Recombinant Proteins
(therapeutic use)
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