title: Safety profile of tinzaparin versus subcutaneous unfractionated heparin in elderly patients with impaired renal function treated for acute deep vein thrombosis: the Innohep® in Renal Insufficiency Study (IRIS).
abstract: BACKGROUND
  Trials comparing the use of full dose unfractionated heparin (UFH) or low molecular weight heparins (LMWHs) in very elderly patients with impaired renal function are lacking. IRIS aimed to assess whether LMWH is at least as safe as UFH in this population.
  
  
  METHODS
  The study included renally impaired patients ≥70 years with acute symptomatic lower limb deep vein thrombosis (DVT). Patients were randomized to initial treatment with either tinzaparin 175 IU/kg once daily (n=269) or activated partial thromboplastin time-adjusted UFH twice daily (n=270). After acute management both groups received vitamin K antagonist to day 90.
  
  
  RESULTS
  The trial was stopped prematurely due to a difference in mortality favoring the UFH group (11.5 vs. 6.3%; p=0.035). Rates of clinically relevant bleedings by day 90 were similar in the tinzaparin (11.9%) and UFH (11.9%) groups, as were rates of confirmed recurrent venous thromboembolism (VTE) (2.6 vs. 1.1%; p=0.34). As the mortality difference could not be explained by bleedings or recurrent VTE, a post-hoc analysis was performed. This identified six baseline characteristics significantly correlated with mortality, of which five were over-represented in the tinzaparin group.
  
  
  CONCLUSIONS
  The IRIS study was a challenging study involving patients (mean age 83 years) usually excluded from clinical studies, but its early termination has left questions unanswered. The mortality difference observed with tinzaparin vs. UFH in elderly, renally-impaired patients with DVT cannot be explained on the basis of bleedings or recurrent VTE, and may reflect an imbalance of mortality risk factors at baseline.
authors.affiliation: Faculté de Médecine Laennec, Service de Pharmacologie, Clinique, Rue Guillaume Paradin, 69008, Lyon, France. al@upcl.univ-lyon1.fr
authors.forename: Alain
authors.initials: A
authors.lastname: Leizorovicz
authors.forename: Virginie
authors.initials: V
authors.lastname: Siguret
authors.forename: Dominique
authors.initials: D
authors.lastname: Mottier
authors.forename: Alain
authors.initials: A
authors.lastname: Leizorovicz
authors.forename: Virginie
authors.initials: V
authors.lastname: Siguret
authors.forename: Dominique
authors.initials: D
authors.lastname: Mottier
authors.forename: Fabrice
authors.initials: F
authors.lastname: Clonier
authors.forename: Mette
authors.initials: M
authors.lastname: Janas
authors.forename: John
authors.initials: J
authors.lastname: Stinson
authors.forename: Grace
authors.initials: G
authors.lastname: Townshend
authors.forename: Michael
authors.initials: M
authors.lastname: Maddalena
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D051437:Renal Insufficiency / Q000150:complications*; D000078222:Tinzaparin; D020246:Venous Thrombosis / Q000150:complications / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D000078222:Tinzaparin; D006493:Heparin