A synthetic factor-Xa inhibitor (ORG31540/SR9017A) as an adjunct to fibrinolysis in acute myocardial infarction. The PENTALYSE study.
BACKGROUND
ORG31540/SR90107A, a synthetic pentasaccharide, is a selective inhibitor of factor-Xa. It was hypothesized that prolonged factor-Xa inhibition with pentasaccharide may be an effective and safe antithrombotic co-therapy in acute myocardial infarction.


RESULTS
Patients (n=333) with evolving ST-segment elevation acute myocardial infarction were treated with aspirin and alteplase and randomized to unfractionated heparin, given intravenously during 48 to 72 h, or to a low, medium or high dose of pentasaccharide, administered daily for 5 to 7 days, intravenously on the first day, then subcutaneously. Coronary angiography was performed at 90 min and on days 5 to 7. Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 rates at 90 min were similar in the four treatment groups. Among patients with TIMI 3 flow at 90 min and who did not undergo a coronary intervention (n=155), a trend towards less reocclusion of the infarct-related vessel on days 5 to 7 was observed with pentasaccharide: 0.9% vs 7.0% with unfractionated heparin (P=0.065). Also, fewer revascularizations during the 30-day follow-up period were performed in patients given pentasaccharide (39% vs 51% for unfractionated heparin;P=0.054). The primary safety end-point, the combined incidence of intracranial haemorrhage and need for blood transfusion, was identical with pentasaccharide and unfractionated heparin (7.1%). One non-fatal intracranial haemorrhage occurred in the 241 patients given pentasaccharide (0.4%).


CONCLUSIONS
In this study, pentasaccharide given together with alteplase was safe and as effective as unfractionated heparin in restoring coronary artery patency. Prolonged administration of pentasaccharide was associated with a trend towards less reocclusion and fewer revascularizations. Selective factor-Xa-inhibition seems to be an attractive therapeutic concept in patients presenting with ST-segment elevation acute myocardial infarction.
Coussement
P K
PK
University Hospital Gasthuisberg, Leuven, Belgium.
Bassand
J P
JP
Convens
C
C
Vrolix
M
M
Boland
J
J
Grollier
G
G
Michels
R
R
Vahanian
A
A
Vanderheyden
M
M
Rupprecht
H J
HJ
Van de Werf
F
F
D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000627:therapeutic use*; D017023:Coronary Angiography; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D005060:Europe / Q000453:epidemiology; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D005500:Follow-Up Studies; D006493:Heparin / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D020300:Intracranial Hemorrhages / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D010314:Partial Thromboplastin Time; D010447:Peptide Hydrolases / Q000097:blood; D012008:Recurrence; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D015912:Thrombolytic Therapy / Q000009:adverse effects; D016896:Treatment Outcome
D015842:Serine Proteinase Inhibitors; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D006493:Heparin; D010447:Peptide Hydrolases