title: Promise of combined low-molecular-weight heparin and platelet glycoprotein IIb/IIIa inhibition: results from Platelet IIb/IIIa Antagonist for the Reduction of Acute coronary syndrome events in a Global Organization Network B (PARAGON B).
abstract: BACKGROUND
  Low-molecular-weight heparin (LMWH) has a more predictable anticoagulant effect than unfractionated heparin (UFH), is easier to administer, and does not require monitoring. Minimal data are available on LMWH combined with platelet glycoprotein (GP) IIb/IIIa inhibitors.
  
  
  METHODS
  In the Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network B (PARAGON B) trial, patients with an acute coronary syndrome were randomized to receive the IIb/IIIa inhibitor lamifiban or a placebo. To rigorously explore the potential benefits of LWMH and GP IIb/IIIa inhibition, we analyzed the rates of ischemic complications and safety outcomes in PARAGON B.
  
  
  RESULTS
  Approximately one fifth of the patients received LMWH (805 vs 4395 UFH). For the overall cohort, the incidence of death/myocardial infarction (MI)/severe recurrent ischemia (SRI) was 12.2%, and this composite end point was numerically lowest in the lamifiban with LMWH group (10.2%). Similarly, the incidence of death/MI was 11.0% for the entire cohort and lowest in the lamifiban and LMWH group (9.0%). The lower event rate for patients taking LMWH in the lamifiban group was sustained at 6 months, with a lower revascularization rate (51.5% vs 42.8%) and a lower composite of death/MI (13.8% vs 11.9%). Bleeding was comparable in the 2 heparin groups (1.4% with UFH vs 0.9% with LMWH). The propensity adjusted odds ratio for 30-day revascularization was significantly lower with LMWH (odds ratio 0.67, 95% CI 0.57-0.79, P <.001). There were no significant differences in death/MI/SRI at 30 days (P =.465), death/MI at 30 days (P =.264), and stroke at 30 days with the type of heparin use (P =.201) after propensity risk adjustment.
  
  
  CONCLUSIONS
  In the PARAGON B trial, use of LMWH in conjunction with a GP IIb/IIIa inhibitor was safe and associated with a lower revascularization rate. These findings support the rationale and promise for combining GP IIb/IIIa blockers and LMWH for future management of acute coronary syndrome.
authors.affiliation: University of Michigan Health System, Ann Arbor, Mich, USA.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Mukherjee
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: David J
authors.initials: DJ
authors.lastname: Moliterno
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Jay S
authors.initials: JS
authors.lastname: Yadav
authors.forename: Karen S
authors.initials: KS
authors.lastname: Pieper
authors.forename: Dianne
authors.initials: D
authors.lastname: Gallup
authors.forename: Christopher
authors.initials: C
authors.lastname: Dyke
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Roe
authors.forename: Lisa
authors.initials: L
authors.lastname: Berdan
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lauer
authors.forename: Matti
authors.initials: M
authors.lastname: Mänttäri
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
mesh_terms: D000085:Acetates / Q000627:therapeutic use*; D000208:Acute Disease; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D003627:Data Interpretation, Statistical; D004359:Drug Therapy, Combination; D005260:Female; D006493:Heparin / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009204:Myocardial Revascularization; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D000085:Acetates; D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D006493:Heparin; C084062:lamifiban