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European Heart Journal 1999 20(22):1657-1666; doi:10.1053/euhj.1999.1750
Copyright © 1999 by the European Society of Cardiology.
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Activated partial thromboplastin time and clinical outcome after thrombin inhibition in unstable coronary artery disease

J. Oldgrena,f1, R. Linderb, L. Gripc, A. Siegbahnd and L. Wallentina

a Department of Cardiology, Uppsala University Hospital, Uppsala
d Department of Laboratory Medicine, Uppsala University Hospital, Uppsala
b Department of Cardiology, Karolinska Hospital, Stockholm
c Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden

revised June 15, 1999; accepted June 16, 1999

Abstract

Aims Direct thrombin inhibitors have failed to prove superiority over unfractionated heparin in several clinical trials of unstable coronary artery disease. We have investigated the relationship between activated partial thromboplastin time levels and adverse clinical events, i.e. death, myocardial (re-)infarction or refractory angina.

Methods and Results One thousand two hundred and nine patients with unstable coronary artery disease were randomized to 72h infusion with inogatran, a low molecular mass direct thrombin inhibitor, or unfractionated heparin. During 30 days follow-up there was no significant difference between inogatran and unfractionated heparin treatment as regards clinical outcome. 11·6% of the 464 inogatran treated patients with activated partial thromboplastin time above the median at 6h (44s) had a clinical event in 7 days, and 6·6% of the 423 patients with activated partial thromboplastin time below the median (P=0·01). After 30 days the event rate was still 41% higher in the inogatran patients with activated partial thromboplastin time above the median (P=0·06). Activated partial thromboplastin time in quartiles indicated a direct relationship between higher activated partial thromboplastin time and worse outcome. In contrast, during heparin infusion there was a trend for improved clinical outcome with activated partial thromboplastin time above the median, but this benefit was lost after cessation of treatment.

Conclusions Higher activated partial thromboplastin time levels during inogatran treatment are related to increased risk of death, myocardial infarction or refractory angina. This might, at least in part, be explained by differences in anticoagulant mechanisms between direct thrombin inhibitors and heparin, and further emphasizes the poorly defined optimal activated partial thromboplastin time range during treatment with direct thrombin inhibitors in unstable coronary artery disease.

Key Words: Anticoagulants, myocardial infarction, prognosis, thrombosis, unstable angina

f1 Correspondence: Jonas Oldgren, MD, Department of Cardiology, Uppsala University Hospital, S-751 85 Uppsala, Sweden.

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