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Evaluation of standard versus reduced dose apixaban for the treatment of venous thromboembolism in patients with severe renal disease (ESRD-VTE)

      Highlights

      • Optimal apixaban dosing for VTE in severe renal disease is currently debated.
      • Rates of bleeding and VTE were compared between standard vs reduced dose apixaban.
      • Clinically relevant bleed rate was significantly lower with reduced dose apixaban.

      Abstract

      Background

      There are no clear dosing recommendations when using apixaban for venous thromboembolism (VTE) treatment in patients with severe or end-stage renal disease; clinical trials excluded patients with a creatinine clearance (CrCl) <25 mL/min or on dialysis. This study compares bleeding rates in patients with severe or end-stage renal disease taking standard versus reduced dose apixaban for VTE treatment.

      Materials and methods

      This was a multicenter, retrospective cohort study using electronic medical records between January 1, 2013, and August 31, 2021. This study included patients 18 years or older who had severe or end-stage renal disease when prescribed apixaban for VTE treatment. Severe or end-stage renal disease was defined as at least one of the following: CrCl <25 mL/min, SCr >2.5 mg/dL, CKD stage 4 or 5, or on dialysis. The primary endpoint was rate of clinically relevant bleeding within six months of starting apixaban. Secondary endpoints were VTE recurrence within six months of starting apixaban, time to clinically relevant bleed, and time to VTE recurrence.

      Results

      A total of 203 patients were included in the final analysis (n = 125 on 5 mg; n = 78 on 2.5 mg). Clinically relevant bleeding rate was significantly higher in the standard dose group (14.4 % vs 3.8 %, p = 0.02). Rates of VTE recurrence appear similar (6.4 % vs 7.7 %, p = 0.21).

      Conclusions

      A reduced dose of apixaban may be considered when treating VTE in patients with severe or end-stage renal disease.

      Keywords

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      References

      1. Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2021. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2021.

        • Wattanakit K.
        • Cushman M.
        • Stehman-Breen C.
        • et al.
        Chronic kidney disease increases risk for venous thromboembolism.
        J Am Soc Nephrol. 2008; 19: 135-140https://doi.org/10.1681/ASN.2007030308
        • Wattanakit K.
        • Cushman M.
        Chronic kidney disease and venous thromboembolism: epidemiology and mechanisms.
        Curr. Opin. Pulm. Med. 2009; 15: 408-412https://doi.org/10.1097/MCP.0b013e32832ee371
        • Stevens S.M.
        • Woller S.C.
        • Baumann Kreuziger L.
        • et al.
        Executive summary: antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report.
        Chest. 2021; 160: 2247-2259https://doi.org/10.1016/j.chest.2021.07.056
        • Ruff C.T.
        • Giugliano R.P.
        • Braunwald E.
        • et al.
        Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.
        Lancet. 2014; 383: 955-962
        • van der Hulle T.
        • Kooiman J.
        • den Exter P.L.
        • et al.
        Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis.
        J. Thromb. Haemost. 2014; 12: 320-328
      2. Eliquis. Package insert. Bristol-Myers Squibb/Pfizer; 2021.

        • Liu X.
        • Johnson M.
        • Mardekian J.
        • et al.
        Apixaban reduces hospitalizations in patients with venous thromboembolism: an analysis of the apixaban for the initial management of pulmonary embolism and deep-vein thrombosis as first-line therapy (AMPLIFY) trial.
        J. Am. Heart Assoc. 2015; 4https://doi.org/10.1161/jaha.115.002340
        • Stanifer J.W.
        • Pokorney S.D.
        • Chertow G.M.
        • et al.
        Apixaban versus warfarin in patients with atrial fibrillation and advanced chronic kidney disease.
        Circ. Res. 2020; 141: 1384-1392https://doi.org/10.1161/CIRCULATIONAHA.119.044059
        • Schafer J.H.
        • Casey A.L.
        • Dupre K.A.
        • et al.
        Safety and efficacy of apixaban versus warfarin in patients with advanced chronic kidney disease.
        Ann. Pharmacother. 2018; 52: 1078-1084https://doi.org/10.1177/1060028018781853
        • Granger C.B.
        • Alexander J.H.
        • McMurray J.J.
        • et al.
        Apixaban versus warfarin in patients with atrial fibrillation.
        N. Engl. J. Med. 2011; 365: 981-992https://doi.org/10.1056/NEJMoa1107039
        • Mavrakanas T.A.
        • Samer C.F.
        • Nessim S.J.
        • et al.
        Apixaban pharmacokinetics at steady state in hemodialysis patients.
        J Am Soc Nephrol. 2017; 28: 2241-2248https://doi.org/10.1681/ASN.2016090980
        • Harris P.A.
        • Taylor R.
        • Thielke R.
        • et al.
        Research electronic data capture (REDCap) – a metadata-driven methodology and workflow process for providing translational research informatics support.
        J. Biomed. Inform. 2009; 42: 377-381
        • Harris P.A.
        • Taylor R.
        • Minor B.L.
        • et al.
        The REDCap consortium: building an international community of software partners.
        J. Biomed. Inform. 2019; https://doi.org/10.1016/j.jbi.2019.103208
        • Schulman S.
        • Kearon C.
        Subcommittee on control of anticoagulation of the scientific and standardization committee of the international society on thrombosis and haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients.
        J. Thromb. Haemost. 2005; 3: 692-694https://doi.org/10.1111/j.1538-7836.2005.01204.x
        • Stanifer J.W.
        • Pokorney S.D.
        • Chertow G.M.
        • et al.
        Apixaban versus warfarin in patients with atrial fibrillation and advanced chronic kidney disease.
        Circ. Res. 2020; 141: 1384-1392https://doi.org/10.1161/CIRCULATIONAHA.119.044059
        • Steuber T.D.
        • Shiltz D.L.
        • Cairns A.C.
        • et al.
        A multicenter analysis of factors associated with apixaban-related bleeding in hospitalized patients with end-stage renal disease on hemodialysis.
        Ann. Pharmacother. 2017; 51: 954-960https://doi.org/10.1177/1060028017717282
        • Chen J.
        • Nguyen S.
        • Ruegger M.
        • et al.
        Evaluation of outcomes with apixaban use for venous thromboembolism in hospitalized patients with end-stage renal disease receiving renal replacement therapy.
        J Thromb. 2022; https://doi.org/10.1007/s11239-022-02650-4
        • Starr J.A.
        • Pinner N.A.
        • Mannis M.
        • et al.
        A review of direct oral anticoagulants in patients with stage 5 or end-stage kidney disease.
        Ann. Pharmacother. 2021; 56: 691-703https://doi.org/10.1177/10600280211040093
        • Reed D.
        • Palkimas S.
        • Hockman R.
        • et al.
        Safety and effectiveness of apixaban compared to warfarin in dialysis patients.
        Res Pract Thromb Haemost. 2018; 2: 291-298https://doi.org/10.1002/rth2.12083
        • Wetmore J.B.
        • Herzog C.A.
        • Yan H.
        • et al.
        Apixaban versus warfarin for treatment of venous thromboembolism in patients receiving long-term dialysis.
        Clin. J. Am. Soc. Nephrol. 2022; 17: 693-702https://doi.org/10.2215/CJN.14021021
        • Schulman S.
        • Rhedin A.
        • Lindmarker P.
        • et al.
        A comparison of six weeks with six months of Oral anticoagulant therapy after a first episode of venous thromboembolism.
        N. Engl. J. Med. 1995; 332: 1661-1665https://doi.org/10.1056/NEJM199506223322501
        • Klok F.A.
        • Barco S.
        • Turpie A.G.
        • et al.
        Predictive value of venous thromboembolism (VTE)-BLEED to predict major bleeding and other adverse events in a practice-based cohort of patients with VTE: results of the XALIA study.
        Br. J. Haematol. 2018; 183: 457-465https://doi.org/10.1111/bjh.15533