PMID- 21477846 OWN - NLM STAT- MEDLINE DCOM- 20111102 LR - 20181201 IS - 1879-2472 (Electronic) IS - 0049-3848 (Linking) VI - 128 IP - 1 DP - 2011 Jul TI - Safety profile of tinzaparin versus subcutaneous unfractionated heparin in elderly patients with impaired renal function treated for acute deep vein thrombosis: the Innohep(R) in Renal Insufficiency Study (IRIS). PG - 27-34 LID - 10.1016/j.thromres.2011.03.002 [doi] AB - INTRODUCTION: 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. MATERIALS AND 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. CONCLUSION: 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. CI - Copyright (c) 2011. Published by Elsevier Ltd. FAU - Leizorovicz, Alain AU - Leizorovicz A AD - Faculte de Medecine Laennec, Service de Pharmacologie, Clinique, Rue Guillaume Paradin, 69008, Lyon, France. al@upcl.univ-lyon1.fr FAU - Siguret, Virginie AU - Siguret V FAU - Mottier, Dominique AU - Mottier D CN - Innohep(R) in Renal Insufficiency Study Steering Committee FAU - Leizorovicz, Alain AU - Leizorovicz A FAU - Siguret, Virginie AU - Siguret V FAU - Mottier, Dominique AU - Mottier D FAU - Clonier, Fabrice AU - Clonier F FAU - Janas, Mette AU - Janas M FAU - Stinson, John AU - Stinson J FAU - Townshend, Grace AU - Townshend G FAU - Maddalena, Michael AU - Maddalena M LA - eng SI - ClinicalTrials.gov/NCT00277394 PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20110407 PL - United States TA - Thromb Res JT - Thrombosis research JID - 0326377 RN - 0 (Anticoagulants) RN - 0 (Heparin, Low-Molecular-Weight) RN - 7UQ7X4Y489 (Tinzaparin) RN - 9005-49-6 (Heparin) SB - IM MH - Aged MH - Aged, 80 and over MH - Anticoagulants/administration & dosage/*adverse effects MH - Drug Administration Schedule MH - Female MH - Heparin/administration & dosage/*adverse effects MH - Heparin, Low-Molecular-Weight/administration & dosage/*adverse effects MH - Humans MH - Male MH - Renal Insufficiency/*complications MH - Tinzaparin MH - Venous Thrombosis/complications/*drug therapy FIR - Leizorovicz, Alain IR - Leizorovicz A FIR - Siguret, Virginie IR - Siguret V FIR - Mottier, Dominique IR - Mottier D FIR - Bauersachs, Rupert IR - Bauersachs R FIR - Ribera Casado, Jose-Manuel IR - Ribera Casado JM FIR - Maksimovic, Zivan IR - Maksimovic Z FIR - Gutowski, Piotr IR - Gutowski P FIR - Fiessinger, Jean Noel IR - Fiessinger JN FIR - Girard, Philippe IR - Girard P FIR - Parent, Florence IR - Parent F FIR - Boddaert, Jacques IR - Boddaert J FIR - Bost, Vincent IR - Bost V FIR - Steg, Gabriel IR - Steg G FIR - Baumelou, Alain IR - Baumelou A FIR - Bounameaux, Henri IR - Bounameaux H FIR - Torres, Ferran IR - Torres F FIR - Matthes, Bettina Kemkes IR - Matthes BK FIR - Tornqvist, Kristine IR - Tornqvist K FIR - Pedersen, Trine Fischer IR - Pedersen TF FIR - Rasmussen, Irene IR - Rasmussen I FIR - Clonier, Fabrice IR - Clonier F FIR - Janas, Mette IR - Janas M FIR - Stinson, John IR - Stinson J EDAT- 2011/04/12 06:00 MHDA- 2011/11/04 06:00 CRDT- 2011/04/12 06:00 PHST- 2010/10/29 00:00 [received] PHST- 2011/03/04 00:00 [revised] PHST- 2011/03/06 00:00 [accepted] PHST- 2011/04/12 06:00 [entrez] PHST- 2011/04/12 06:00 [pubmed] PHST- 2011/11/04 06:00 [medline] AID - S0049-3848(11)00114-9 [pii] AID - 10.1016/j.thromres.2011.03.002 [doi] PST - ppublish SO - Thromb Res. 2011 Jul;128(1):27-34. doi: 10.1016/j.thromres.2011.03.002. Epub 2011 Apr 7.