PMID- 17599602
OWN - NLM
STAT- MEDLINE
DCOM- 20070723
LR  - 20070629
IS  - 1558-3597 (Electronic)
IS  - 0735-1097 (Linking)
VI  - 49
IP  - 25
DP  - 2007 Jun 26
TI  - Recombinant nematode anticoagulant protein c2 in patients with non-ST-segment 
      elevation acute coronary syndrome: the ANTHEM-TIMI-32 trial.
PG  - 2398-407
AB  - OBJECTIVES: We sought to evaluate the safety and efficacy of recombinant nematode 
      anticoagulant protein c2 (rNAPc2) in patients with non-ST-segment elevation acute 
      coronary syndrome (nSTE-ACS). BACKGROUND: Recombinant NAPc2 is a potent inhibitor 
      of the tissue factor/factor VIIa complex that has the potential to reduce 
      ischemic complications mediated by thrombin generation. METHODS: A total of 203 
      patients were randomized 4:1 to double-blinded intravenous rNAPc2 or placebo 
      every 48 h for a total of 1 to 3 doses in 8 ascending panels (1.5 to 10 
      microg/kg). All patients received aspirin, unfractionated heparin (UFH), or 
      enoxaparin and early catheterization; clopidogrel and glycoprotein IIb/IIIa 
      blockers were encouraged. Two subsequent open-label panels evaluated 10 mug/kg 
      rNAPc2 with half-dose UFH (n = 26) and no UFH (n = 26). The primary end point was 
      the rate of major plus minor bleeding. Pharmacokinetics, pharmacodynamics, 
      continuous electrocardiography, and clinical events were assessed. RESULTS: 
      Recombinant NAPc2 did not significantly increase major plus minor bleeding (3.7% 
      vs. 2.5%; p = NS) despite increasing the international normalized ratio in a 
      dose-related fashion (trend p < or = 0.0001). Higher-dose rNAPc2 (> or =7.5 
      microg/kg) suppressed prothrombin fragment F1.2 generation compared with placebo 
      and reduced ischemia by >50% compared to placebo and lower-dose rNAPc2. 
      Thrombotic bailout requiring open-label anticoagulant occurred in 5 of 26 
      patients treated without UFH, but none in the half-dose UFH group (19% vs. 0%; p 
      = 0.051). CONCLUSIONS: In patients with nSTE-ACS managed with standard 
      antithrombotics and an early invasive approach, additional proximal inhibition of 
      the coagulation cascade with rNAPc2 was well tolerated. rNAPc2 doses > or =7.5 
      microg/kg suppressed F1.2 and reduced ischemia, though some heparin may be 
      necessary to avoid procedure-related thrombus formation. (Anticoagulation With 
      rNAPc2 to Eliminate MACE/TIMI 32; 
      http://www.clinicaltrial.gov/ct/show/NCT00116012?order=1; NCT00116012).
FAU - Giugliano, Robert P
AU  - Giugliano RP
AD  - TIMI Study Group, Boston, Massachusetts 02115, USA. rgiugliano@partners.org
FAU - Wiviott, Stephen D
AU  - Wiviott SD
FAU - Stone, Peter H
AU  - Stone PH
FAU - Simon, Daniel I
AU  - Simon DI
FAU - Schweiger, Marc J
AU  - Schweiger MJ
FAU - Bouchard, Alain
AU  - Bouchard A
FAU - Leesar, Massoud A
AU  - Leesar MA
FAU - Goulder, Michael A
AU  - Goulder MA
FAU - Deitcher, Steven R
AU  - Deitcher SR
FAU - McCabe, Carolyn H
AU  - McCabe CH
FAU - Braunwald, Eugene
AU  - Braunwald E
CN  - ANTHEM-TIMI-32 Investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT00116012
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20070611
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Helminth Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (anti-coagulant protein C2, Ancylostoma caninum)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Coronary Angiography
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - *Electrocardiography
MH  - Female
MH  - Follow-Up Studies
MH  - Helminth Proteins/*administration & dosage
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Myocardial Infarction/*diagnosis/*drug therapy/mortality
MH  - Pilot Projects
MH  - Recombinant Proteins/administration & dosage
MH  - Risk Assessment
MH  - Severity of Illness Index
MH  - Treatment Outcome
EDAT- 2007/06/30 09:00
MHDA- 2007/07/24 09:00
CRDT- 2007/06/30 09:00
PHST- 2007/01/03 00:00 [received]
PHST- 2007/01/31 00:00 [revised]
PHST- 2007/02/12 00:00 [accepted]
PHST- 2007/06/30 09:00 [pubmed]
PHST- 2007/07/24 09:00 [medline]
PHST- 2007/06/30 09:00 [entrez]
AID - S0735-1097(07)01202-8 [pii]
AID - 10.1016/j.jacc.2007.02.065 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2007 Jun 26;49(25):2398-407. doi: 10.1016/j.jacc.2007.02.065. 
      Epub 2007 Jun 11.