PMID- 19194284
OWN - NLM
STAT- MEDLINE
DCOM- 20090604
LR  - 20181201
IS  - 1473-5830 (Electronic)
IS  - 0954-6928 (Linking)
VI  - 20
IP  - 2
DP  - 2009 Mar
TI  - Streamlining the design of promising clinical trials: in-vitro testing of 
      antithrombotic regimens and multiple agonists of platelet activation.
PG  - 175-8
LID - 10.1097/MCA.0b013e32831edcd1 [doi]
AB  - Platelets are activated in vivo by multiple agonists; however, platelet function 
      testing in vitro has been performed predominantly with only one or two agonists 
      of platelet activation. Greater insight into anticipated effects of 
      antithrombotic regimens should enhance the design of successful clinical trials. 
      To test this concept, we assessed platelet activation induced by multiple 
      agonists and two antithrombotic regimens, unfractionated heparin (UFH) and 
      eptifibatide compared with bivalirudin and cangrelor. Blood samples from 10 
      patients with coronary artery disease were spiked with pharmacologic 
      concentrations achieved in vivo of either UFH (1.2 U/ml) and eptifibatide (1.7 
      microg/ml), or with bivalirudin (8 microg/ml) and cangrelor (500 nmol/l). 
      Platelet function was assessed with the use of flow cytometry. Agonists included 
      thrombin (50 nmol/l), adenosine diphosphate (1 micromol/l), the collagen-mimetic 
      convulxin (5 ng/ml), and platelet-activating factor (10 nmol/l). When platelet 
      activation was identified by the surface expression of P-selectin in response to 
      multiple agonists, the combination of bivalirudin and cangrelor suppressed 
      activation more than UFH and eptifibatide. When platelet activation was 
      identified by the activation of glycoprotein IIb-IIIa (PAC-1 binding), the 
      combination of bivalirudin and cangrelor was more effective in suppressing 
      activation in response to thrombin and adenosine diphosphate, whereas UFH and 
      eptifibatide more effectively prevented binding of PAC-1 when platelets were 
      activated with the collagen-mimetic convulxin. In conclusion, bivalirudin and 
      cangrelor suppressed platelet activation in response to diverse agonists in vitro 
      more than UFH and eptifibatide. These results and this approach to selection of 
      promising interventions should be helpful in streamlining the design of clinical 
      trials.
FAU - Schneider, David J
AU  - Schneider DJ
AD  - Department of Medicine, Cardiology Unit and Cardiovascular Research Institute, 
      University of Vermont, Burlington, Vermont 05446, USA. david.schneider@uvm.edu
FAU - Sobel, Burton E
AU  - Sobel BE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Coron Artery Dis
JT  - Coronary artery disease
JID - 9011445
RN  - 0 (Crotalid Venoms)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Hirudins)
RN  - 0 (Lectins, C-Type)
RN  - 0 (P-Selectin)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Recombinant Proteins)
RN  - 37206-04-5 (convulxin)
RN  - 415SHH325A (Adenosine Monophosphate)
RN  - 61D2G4IYVH (Adenosine Diphosphate)
RN  - 6AQ1Y404U7 (cangrelor)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.5 (Thrombin)
RN  - NA8320J834 (Eptifibatide)
RN  - TN9BEX005G (bivalirudin)
SB  - IM
MH  - Adenosine Diphosphate
MH  - Adenosine Monophosphate/analogs & derivatives/pharmacology
MH  - Animals
MH  - Blood Platelets/*drug effects/metabolism
MH  - Clinical Trials as Topic/*methods
MH  - Coronary Artery Disease/blood/*drug therapy
MH  - Crotalid Venoms
MH  - Drug Evaluation, Preclinical/*methods
MH  - Drug Therapy, Combination
MH  - Eptifibatide
MH  - Fibrinolytic Agents/*pharmacology
MH  - Flow Cytometry
MH  - Heparin/pharmacology
MH  - Hirudins/pharmacology
MH  - Humans
MH  - Lectins, C-Type
MH  - P-Selectin/blood
MH  - Peptide Fragments/pharmacology
MH  - Peptides/pharmacology
MH  - Pilot Projects
MH  - Platelet Activating Factor
MH  - Platelet Activation/*drug effects
MH  - *Platelet Function Tests
MH  - Recombinant Proteins/pharmacology
MH  - *Research Design
MH  - Thrombin
EDAT- 2009/02/06 09:00
MHDA- 2009/06/06 09:00
CRDT- 2009/02/06 09:00
PHST- 2009/02/06 09:00 [entrez]
PHST- 2009/02/06 09:00 [pubmed]
PHST- 2009/06/06 09:00 [medline]
AID - 10.1097/MCA.0b013e32831edcd1 [doi]
PST - ppublish
SO  - Coron Artery Dis. 2009 Mar;20(2):175-8. doi: 10.1097/MCA.0b013e32831edcd1.