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)

  • Author Footnotes
    1 On behalf of the IRIS (Innohep® in Renal Insufficiency Study) Steering Committee.
    Alain Leizorovicz
    Correspondence
    Corresponding author at: Faculté de Médecine Laennec, Service de Pharmacologie Clinique, Rue Guillaume Paradin, 69008, Lyon, France. Tel.: +33 4 7878 5759; fax: +33 4 7877 6917.
    Footnotes
    1 On behalf of the IRIS (Innohep® in Renal Insufficiency Study) Steering Committee.
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  • Author Footnotes
    1 On behalf of the IRIS (Innohep® in Renal Insufficiency Study) Steering Committee.
    Virginie Siguret
    Footnotes
    1 On behalf of the IRIS (Innohep® in Renal Insufficiency Study) Steering Committee.
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  • Author Footnotes
    1 On behalf of the IRIS (Innohep® in Renal Insufficiency Study) Steering Committee.
    Dominique Mottier
    Footnotes
    1 On behalf of the IRIS (Innohep® in Renal Insufficiency Study) Steering Committee.
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  • Author Footnotes
    1 On behalf of the IRIS (Innohep® in Renal Insufficiency Study) Steering Committee.

      Abstract

      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.

      Abbreviations:

      ACCP (American College of Chest Physicians), ADR (adverse drug reaction), AE (adverse event), APTT (activated partial thromboplastin time), BMI (body mass index), CI (confidence interval), CRB (clinically relevant bleedings), CrCl (creatinine clearance), CEC (Critical Event Committee), COPD (chronic obstructive pulmonary disease), DMC (Data Monitoring Committee), DVT (deep vein thrombosis), GIST (gastrointestinal stromal tumor), HIT (heparin-induced thrombocytopenia), INR (international normalized ratio), IRIS (Innohep® in Renal Insufficiency Study), IV (intravenous), LMWH (low molecular weight heparin), NIM (non-inferiority margin), NSAID (non-steroidal anti-inflammatory drug), PE (pulmonary embolism), RR (relative risk), SC (subcutaneous), SAE (serious adverse event), UFH (unfractionated heparin), VKA (vitamin K antagonist), VQ scan (ventilation/perfusion scan), VTE (venous thromboembolism)

      Keywords

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