PMID- 21045018
OWN - NLM
STAT- MEDLINE
DCOM- 20110523
LR  - 20110201
IS  - 1753-9455 (Electronic)
IS  - 1753-9447 (Linking)
VI  - 5
IP  - 1
DP  - 2011 Feb
TI  - New parenteral anticoagulants in development.
PG  - 33-59
LID - 10.1177/1753944710387808 [doi]
AB  - The therapeutic armamentarium of parenteral anticoagulants available to 
      clinicians is mainly composed by unfractionated heparin (UFH), 
      low-molecular-weight heparin (LMWH), fondaparinux, recombinant hirudins (i.e. 
      bivalirudin, desirudin, lepirudin) and argatroban. These drugs are effective and 
      safe for prevention and/or treatment of thromboembolic diseases but they have 
      some drawbacks. Among other inconveniences, UFH requires regular anticoagulant 
      monitoring as a result of variability in the anticoagulant response and there is 
      a risk of serious heparin-induced thrombocytopaenia (HIT). LMWH, fondaparinux and 
      recombinant hirudins are mainly cleared through the kidneys and their use in 
      patients with severe renal insufficiency may be problematic. LMWH is only 
      partially neutralized by protamine while fondaparinux and recombinant hirudins 
      have no specific antidote. Novel anticoagulants in development for parenteral 
      administration include new indirect activated factor Xa (FXa) inhibitors 
      (idrabiotaparinux, ultra-low-molecular-weight heparins [semuloparin, RO-14], new 
      LMWH [M118]), direct FXa inhibitors (otamixaban), direct FIIa inhibitors 
      (flovagatran sodium, pegmusirudin, NU172, HD1-22), direct FXIa inhibitors 
      (BMS-262084, antisense oligonucleotides targeting FXIa, clavatadine), direct FIXa 
      inhibitors (RB-006), FVIIIa inhibitors (TB-402), FVIIa/tissue factor inhibitors 
      (tifacogin, NAPc2, PCI-27483, BMS-593214), FVa inhibitors (drotrecogin alpha 
      activated, ART-123) and dual thrombin/FXa inhibitors (EP217609, tanogitran). 
      These new compounds have the potential to complement established parenteral 
      anticoagulants. In the present review, we discuss the pharmacology of new 
      parenteral anticoagulants, the results of clinical studies, the newly planned or 
      ongoing clinical trials with these compounds, and their potential advantages and 
      drawbacks over existing therapies.
FAU - Gomez-Outes, Antonio
AU  - Gomez-Outes A
AD  - Division of Pharmacology and Clinical Evaluation, Medicines for Human Use, 
      Spanish Agency for Medicines and Health Care Products (AEMPS), Parque Empresarial 
      Las Mercedes, Edificio 8, C/Campezo 1, Madrid, 28022, Spain. agomezo@aemps.es
FAU - Suarez-Gea, Maria Luisa
AU  - Suarez-Gea ML
FAU - Lecumberri, Ramon
AU  - Lecumberri R
FAU - Rocha, Eduardo
AU  - Rocha E
FAU - Pozo-Hernandez, Carmen
AU  - Pozo-Hernandez C
FAU - Vargas-Castrillon, Emilio
AU  - Vargas-Castrillon E
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20101102
PL  - England
TA  - Ther Adv Cardiovasc Dis
JT  - Therapeutic advances in cardiovascular disease
JID - 101316343
RN  - 0 (Anticoagulants)
RN  - 0 (Antidotes)
RN  - 0 (Drugs, Investigational)
SB  - IM
MH  - Animals
MH  - Anticoagulants/*administration & dosage/adverse effects/chemistry
MH  - Antidotes/therapeutic use
MH  - Blood Coagulation/*drug effects
MH  - Drug Design
MH  - Drugs, Investigational/*administration & dosage/adverse effects/chemistry
MH  - Hemorrhage/chemically induced/prevention & control
MH  - Humans
MH  - Infusions, Parenteral
MH  - Injections
MH  - Risk Assessment
MH  - Treatment Outcome
EDAT- 2010/11/04 06:00
MHDA- 2011/05/24 06:00
CRDT- 2010/11/04 06:00
PHST- 2010/11/04 06:00 [entrez]
PHST- 2010/11/04 06:00 [pubmed]
PHST- 2011/05/24 06:00 [medline]
AID - 1753944710387808 [pii]
AID - 10.1177/1753944710387808 [doi]
PST - ppublish
SO  - Ther Adv Cardiovasc Dis. 2011 Feb;5(1):33-59. doi: 10.1177/1753944710387808. Epub 
      2010 Nov 2.