A dose-finding study of fondaparinux in patients with non-ST-segment elevation acute coronary syndromes: the Pentasaccharide in Unstable Angina (PENTUA) Study.
OBJECTIVE
In this dose-finding study, we sought to compare fondaparinux with enoxaparin in patients with acute coronary syndromes (ACS).


BACKGROUND
Fondaparinux is a synthetic pentasaccharide that selectively inhibits activated clotting factor X. It has been demonstrated as effective in preventing thromboembolic complications in orthopedic surgery.


METHODS
Four doses fondaparinux (2.5, 4, 8, or 12 mg once daily) and enoxaparin (1 mg/kg twice daily) were compared, both given for three to seven days, in patients with ACS without persistent ST-segment elevation.


RESULTS
The rates of the combined primary end point of death, myocardial infarction, or recurrent ischemia after nine days were 27.9%, 35.9%, 34.7%, 30.3%, and 35.7% in patients allocated to fondaparinux doses of 2.5, 4, 8, and 12 mg and enoxaparin, respectively (p = NS). In the per-protocol analysis (929 patients who received adequate study drug and had adequate ST-segment monitoring), these figures were 30.0%, 43.5%, 41.0%, 34.8%, and 40.2%. Again, no dose response was observed. The lowest event rates were observed in the 2.5-mg fondaparinux group, which had significantly lower rates than the enoxaparin group as well as for 4 and 8 mg fondaparinux in the per-protocol analysis (p < 0.05). Bleeding rates were low and not different among the patient groups. No differences were observed in fondaparinux concentrations in patients with or without death, myocardial infarction, recurrent ischemia, or bleeding events.


CONCLUSIONS
This dose-finding study revealed no dose response for different fondaparinux doses ranging from 2.5 to 12 mg subcutaneously and suggests that the efficacy and safety of fondaparinux may be similar to that of enoxaparin. Further studies with fondaparinux in ACS might include the lowest dose (2.5 mg) investigated in this study.
Simoons
Maarten L
ML
Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands. m.simoons@erasmusmc.nl
Bobbink
Inge W G
IW
Boland
Jean
J
Gardien
Martin
M
Klootwijk
Peter
P
Lensing
Anthonie W A
AW
Ruzyllo
Witold
W
Umans
Victor A W M
VA
Vahanian
Alec
A
Van De Werf
Frans
F
Zeymer
Uwe
U
D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D015906:Angioplasty, Balloon, Coronary; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D017984:Enoxaparin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D000077425:Fondaparinux; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis; D013577:Syndrome; D016896:Treatment Outcome; D020107:Troponin T / Q000097:blood
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D000960:Hypolipidemic Agents; D007527:Isoenzymes; D011134:Polysaccharides; D020107:Troponin T; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form; D000077425:Fondaparinux