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European Heart Journal 1997 18(3):443-449;
Copyright © 1997 by the European Society of Cardiology.
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© 1997 The European Society of Cardiology

Antithrombin III supplementation for patients undergoing PTCA for unstable angina pectoris

A controlled randomized double-blind pilot study

L. Grip*,, M. Blombäck{dagger}, N. Egberg{dagger}, Å. Olsson*, B. Svane{ddagger} and M. Velander{ddagger}

*Department of Cardiology, Karolinska Hospital Stockholm, Sweden
{dagger}Department of Blood Coagulation and Chemistry, Karolinska Hospital Stockholm, Sweden
{ddagger}Department of Thoracic Radiology, Karolinska Hospital Stockholm, Sweden

Received 10 May 1996; accepted 19 May 1996.

Correspondence: Lars Grip, MD, PhD, Division of Cardiology, Sahlgrenska Hospital, S-41345 Göteborg, Sweden

Abstract

BACKGROUND: Thrombin activation may be a higher risk for complications and restenosis after percutaneous transluminal coronary angioplasty in unstable patients than in patients with stable angina pectoris. The effects of heparin may be partly counteracted by a decrease in antithrombin (III). The primary objectives of this study were to evaluate whether a subnormal antithrombin level was associated with a hypercoagulable state and to evaluate the effects of antithrombin supplementation, before and after percutaneous transluminal coronary angioplasty, on biochemical signs of coagulation activation. Secondary objectives were to evaluate acute complications and restenosis rate at 3 months.

METHODS: In a double-blind pilot study, 50 patients with unstable angina, with ongoing heparin infusion and with subnormal antithrombin levels (<85%) were randomized to receive antithrombin supplementation or placebo. Treatment targeted to an antithrombin level of 120% was started with a 2 h intravenous infusion before the percutaneous transluminal coronary angioplasty and was repeated, if there were further subnormal values, every 12th hour for 48 h.

RESULTS: Angiographic success was 20/25 in the antithrombin group and 21/25 in the placebo group (ns). Abrupt closure occurred in two and one patients in the two groups, respectively. Activation of coagulation measured as elevations of prothrombin fragment 1+2, thrombinantithrombin complexes and fibrin D-dimer was seen 2 days after the procedure. Baseline levels of fibrin D-dimer were 68 ± 69 µg. 1–1 in the antithrombin group vs 71 ± 46 µg. 1–1 in the placebo group (ns). Two days after percutaneous transluminal coronary angioplasty the levels increased to 135 ±103 vs 242 ± 150 µg. 1–1, respectively (P<0·05 between the groups). Restenosis at 3 months occurred in 4/20 antithrombin patients and in 8/21 placebo patients (ns).

CONCLUSION: In unstable angina patients with heparin treatment and subnormal antithrombin levels, antithrombin supplementation resulted in less activation of coagulation and a tendency towards less restenosis.

Key Words: Percutaneous transluminal coronary angioplasty • antithrombin • hypercoagulability • restenosis • fibrin D-dimer


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