Antithrombin III supplementation for patients undergoing PTCA for unstable angina pectoris. A controlled randomized double-blind pilot study.
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 2h 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, thrombin-antithrombin complexes and fibrin D-dimer was seen 2 days after the procedure. Baseline levels of fibrin D-dimer were 68 +/- 69 micrograms.l-1 in the antithrombin group vs 71 +/- 46 micrograms.l-1 in the placebo group (ns). Two days after percutaneous transluminal coronary angioplasty the levels increased to 135 +/- 103 vs 242 +/- 150 micrograms.l-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).


CONCLUSIONS
In unstable angina patients with heparin treatment and subnormal antithrombin levels, anti-thrombin supplementation resulted in less activation of coagulation and a tendency towards less restenosis.
Grip
L
L
Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.
Blombäck
M
M
Egberg
N
N
Olsson
A
A
Svane
B
B
Velander
M
M
D000789:Angina, Unstable / Q000097:blood / Q000000981:diagnostic imaging / Q000628:therapy*; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use; D000990:Antithrombin III / Q000008:administration & dosage / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000032:analysis; D003131:Combined Modality Therapy; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000628:therapy; D004311:Double-Blind Method; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012008:Recurrence
D000925:Anticoagulants; D001779:Blood Coagulation Factors; D000990:Antithrombin III; D006493:Heparin