Venous Thromboembolism Venous Thromboembolism Venous

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					Low Molecular Weight Heparin versus
Unfractionated Heparin for Prophylaxis                                             Venous Thromboembolism
   of Venous Thromboembolism in                                                    Deep Vein Thrombosis & Pulmonary Embolism
          Medicine Patients
     A Pharmacoeconomic Analysis                                              !   VTE is associated with significant morbidity,
                                                                                  mortality, and resource expenditure in
                                                                                  hospitalized patients
                                                                              !   Predominantly complicates care of non-
                                                                                  surgical patients

         Kerry Wilbur, BScPharm, ACPR, PharmD                                 !   Heterogeneous medicine population possess
         Assistant Professor, College of Pharmacy                     Title       diversity of intrinsic and extrinsic risk factors

                    Faculty Seminar Series
                      December 3, 2008

      Venous Thromboembolism                                                       Venous Thromboembolism
      Deep Vein Thrombosis & Pulmonary Embolism                                    UFH and LMWH thromboprophylaxis

                                                    Virchow’s Triad


      Venous Thromboembolism                                                       Venous Thromboembolism
      Deep Vein Thrombosis & Pulmonary Embolism                                    Deep Vein Thrombosis & Pulmonary Embolism

 !    Prevention of in-hospital VTE is identified
      internationally as a priority to improve patient                        !   Thromboprophylaxis with either low-dose
      safety                                                                      unfractionated heparin or low molecular
 !    In September 2008, the U.S. Surgeon                                         weight heparin is advocated for hospitalized
      General issued a nation-wide “call to                                       medicine patients
      action” to increase awareness about
      DVT and PE and stimulate evidence-
      based practices and research on
      causes, prevention and treatment of
      this public health problem                                                                   American College of Chest Physicians (ACCP)
                                                                                          Antithrombotic and Thrombolytic Therapy, 8th edition. ACCP Guidelines
            US Department of Health and Human Services
    Pharmacoeconomic Analysis                                                  LMWH vs UFH
!   Meta-analysis of UFH vs LMWH in medicine                                   Meta Analysis
    patients showed no difference in incidence
    of DVT, PE, or death

!   LMWH was associated with a 52% relative
    reduction in major bleeding (p=0.049)

!   Absolute major bleeding rate still very low
    27/2,226 UFH (1.2%) and 10/2,243 LMWH (0.44%)

                                                                                                       Mismetti P et al. Thromb Haemost 2000;83:14-9

    Heparin Thromboprophylaxis                                                 Pharmacoeconomic Analysis
        Feature                UFH                  LMWH                       ICER Explained
        administration         SC                   SC                     !   Decision analysis provides a structured
                               10,000 Unit MDV      single dose syringes
                                                    300 mg/3mL MDV
                                                                               process for comparing costs and consequences
        frequency              BID-TID              daily                      of alternative treatment strategies
        renal function         "                    "
                                                    ok in prophylaxis
                                                                                   Cost:     A $20 - B $5 = $15                  ICER +
        pregnancy              "                    "
                                                                                   Efficacy: A 0.90 - B 0.70 0.20
        monitoring             aPTT                 anti Xa                        Cost:     A $5 - B $20 = -$15                 ICER -
                               not in prophylaxis   not in prophylaxis             Efficacy: A 0.90 - B 0.70 0.20
        HIT                    low (~0.5-1.0%)      lower? (~0.5-1.0%)
                                                                                   Cost:     A $20 - B $5 =      $15             ICER -
        cost                   $3.50                $6.04
                                                                                   Efficacy: A 0.70 - B 0.90    -0.20
        MDV: multi-dose vial
                                                                                   Cost:     A $5 - B $20 =     -$15             ICER +
                                                                                   Efficacy: A 0.70 - B 0.90    -0.20

     Pharmacoeconomic Analysis                                                 LMWH vs UFH
     Cost-Effectiveness Plane                                                  Pharmacoeconomic Analyses
            NW                                                             !   Cost-effective strategies have been identified
                                                                               to prevent VTE in patients following knee
                                                                               and hip arthroplasty, surgery and trauma

                                                                               Other groups have found LMWH to be cost

                                                                               neutral or cost saving when compared to UFH
                                                                               in the medicine population from European
                                                                               and American economic perspectives
                                            Dominant Strategy
              SW                                             SE
    LMWH vs UFH                                              LMWH vs UFH
    Objective                                                Methods
                                                         !   Decision analysis model used to compare
!   To determine incremental cost-effectiveness
                                                             enoxaparin 40 mg SC daily with UFH 5,000 Units
    of LMWH relative to UFH for prevention of                twice daily
    VTE in adult medicine patients
                                                         !   Institutional perspective
                                                         !   Period of hospitalization time horizon
                                                         !   Base case scenario of interest was costs per any
                                                             untoward effect averted (DVT, PE, major bleeding,

    LMWH vs UFH                                          Doritos vs Cheetos
    Decision Tree                                        Decision Tre(at)


                                                        Got the                 Orange

                                                                Satiety                   Still hungry...

    LMWH vs UFH                                              LMWH vs UFH
    Methods                                                  Methods
!   Patients in the model were assumed to be             !   All costs were assessed in 2006 Canadian dollars
    routinely monitored for DVT symptoms (clinically)    !   Only direct medial costs resulting from
!   Suspected DVT were confirmed by diagnostic               thromboprophylaxis and management of ADR
    screening (detection probabilities modelled)             were assessed (including prolonged hospitalization)

!   DVT treatment same regardless of prophylaxis         !   Drug and diagnostic costs were obtained from
                                                             Vancouver General Hospital and the BC Medical
!   Probability of PE (and its accurate diagnosis) in        Association Guide to Fees (2006)
    patients with detected and undetected DVT was        !   Other costs obtained from published
    modelled                                                 pharmacoeconomic analyses
    LMWH vs UFH                                                                          LMWH vs UFH
    Methods                                                                              Results
!   At-risk hospitalized patients would be identified on                                 Compared with UFH, LMWH was associated with:
    day 1 and treated for length of stay (7 days)
                                                                                     !   $4,345 reduction in costs
!   One-way analysis performed varying drug costs,                                   !   3.7 fewer untoward events
    PE or major bleeding management costs, baseline
                                                                                     !   incremental cost effectiveness ratio (ICER)
    DVT rate and progression to PE if not treated
                                                                                         of -1,081
!   Sensitivity analyses evaluated cost-effectiveness in
    subgroups of medicine patients: age >75                                          !   LMWH was cost-effective in almost all medicine
                                                               prior DVT                 patients subgrouped according to VTE risk
                                                               respiratory disease

    LMWH vs UFH                                                                          LMWH vs UFH
    Results                                                                              Results
      Group                                    ICER                   ICER                                     $40.0
                                              (DVT/PE)          (All events)
                                                                                            Incremental Cost
      Base Case                                -1,659                 -1081                                    $20.0
      Age > 75 years                           -1,734                 -1,316                                   $10.0

      Malignancy                               -2,692                 -2,166                                     $0.0
      History of DVT                           -3,245                 -2,294
      Infection                                -2,783                 -2,222
      Respiratory Disease                       -60                    417                                     -$40.0
!   Increasing baseline DVT rate in the sensitivity                                                            -$60.0
                                                                                                                    -0.0170     -0.0070    0.0030        0.0130
    analysis shifted cost-saving in this group                                                                                Incremental Effectiveness
                                                                                                                                 (all untoward events)

    LMWH vs UFH                                                                          LMWH vs UFH
    Results                                                                              Discussion
         Net monetary benefit sensitivity analysis                                   !   Our results are consistent with other European

                                                                                         studies conducted in the medicine population

                       12.0                                                          !   Our model was robust through analyses
            Cost UFH

                                                                                         varying efficacy and safety outcome probability


                        6.0                                                              and outcomes in at-risk medicine subgroups


                           0.0   4.0    8.0     12.0   16.0   20.0

                                       Cost LMWH
!   UFH becomes cost-effective only when acquisition
    cost for daily treatment > ! $5 vs LMWH
     LMWH vs UFH                                                                                       LMWH vs UFH
     Discussion                                                                                        Conclusion
!    Cost-effectiveness is valuable information, yet                                               !   LMWH is the cost-effective alternative to UFH
     current emphasis is on actual administration
                                                                                                       for thromboprophylaxis in hospitalized
     of any appropriate thromboprophylaxis strategy
                                                                                                       medicine patients in Canada
                                                                                                   !   LMWH is the dominant thromboprophylaxis
                                                                                                       strategy across a number of at-risk subgroups
                                                                                                       within this heterogeneous patient population
                                                                                                   !   Greater acquisition cost should not be a
                                                                                                       deterrent to LMWH use for this indication

                                   Patel K, Loewen PS, Wilbur K. Can J Hosp Pharm 2006;59:258-63

!    This study was funded in part by a research
     Grant awarded by the Canadian Society of
     Hospital Pharmacists (CSHP) Research &
     Education Foundation

!    Larry Lynd, BSP PhD1,2
     Mohsen Sadatsafavi MD, MSc2
1.   Faculty Pharmaceutical Sciences, UBC
2.   Centre for Evaluation of Outcome Sciences (CHEOS)