Comparison of effects on markers of blood cell activation of enoxaparin, dalteparin, and unfractionated heparin in patients with unstable angina pectoris or non-ST-segment elevation acute myocardial infarction (the ARMADA study).
The low-molecular-weight heparins (LMWHs) enoxaparin and dalteparin have shown superior and equivalent efficacy, respectively, over unfractionated heparin (UFH) in patients with unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI). This study aimed to identify markers of blood cell activation that are independent predictors of outcomes at 1 month and to compare the effects of enoxaparin, dalteparin, and UFH on any such markers. In this multicenter, prospective, open-label study, 141 patients with UAP or NSTEMI were randomized to treatment for 48 to 120 hours with enoxaparin (n = 46), dalteparin (n = 48), or UFH (n = 47). Blood samples were taken at the time of randomization and after > or =48 hours of treatment but before catheterization. Multivariate analysis identified increased plasma levels of von Willebrand factor (vWF) and decreased platelet levels of glycoprotein Ib/IX complexes as independent predictors of 1-month adverse outcome (a composite of death, myocardial infarction, and recurrent ischemia). vWF release was strongly related to and may have been released by inflammation as measured by C-reactive protein. Both LMWHs reduced the release of vWF in plasma (as well as C-reactive protein) compared with UFH. Enoxaparin had a more favorable effect on glycoprotein Ib/IX complexes than either dalteparin or UFH. The incidence of the composite clinical efficacy end point was: 13% (enoxaparin), 19% (dalteparin), and 28% (UFH). vWF and its receptor glycoprotein Ib/IX play a key role in acute coronary syndromes. vWF is linked to inflammation and, like glycoprotein Ib/IX, is affected more favorably by the LWMHs than by UFH.
Montalescot
Gilles
G
Institut de Cardiologie, Bureau 2-236, Groupe Hospitalier Pitié-Salpêtrière Hospital, AP-HP, 47 Boulevard de l'Hôpital, 75013 Paris, France. gilles.montalescot@psl.ap-hop-paris.fr
Bal-dit-Sollier
Claire
C
Chibedi
Daniela
D
Collet
Jean-Philippe
JP
Soulat
Thierry
T
Dalby
Miles
M
Choussat
Rémi
R
Cohen
Ariel
A
Slama
Michel
M
Steg
Phillipe-Gabriel
PG
Dubois-Randé
Jean-Luc
JL
Metzger
Jean-Philippe
JP
Tarragano
François
F
Guermonprez
Jean L
JL
Drouet
Ludovic
L
D000789:Angina, Unstable / Q000097:blood / Q000188:drug therapy*; D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D001792:Blood Platelets / Q000737:chemistry; D017985:Dalteparin / Q000494:pharmacology*; D017984:Enoxaparin / Q000494:pharmacology*; D005260:Female; D006493:Heparin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000032:analysis*; D011446:Prospective Studies; D014841:von Willebrand Factor / Q000032:analysis*
D000925:Anticoagulants; D015415:Biomarkers; D017984:Enoxaparin; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D006493:Heparin; D017985:Dalteparin