VTE Prophylaxis in the Hospitalized Patient: Importance and Strategies for Improved Compliance

1
VTE Prophylaxis in the Hospitalized Patient
Importance and Strategies for Improved Compliance

• Andrew H. Dombro, M.D.
• Instructor of Medicine
• Division of General Internal Medicine, Hospital
  Medicine Section
• University of Colorado Health Sciences Center

2
Overview

• Background / Prevalence of VTE
• Benefits / Rationale for VTE prophylaxis
• Identification of hospitalized patients most at
  risk
• Methods of VTE prophylaxis
• National Consensus Standards for Prevention and
  Care of VTE (CMS as well?)
• Factors related to under-use of established
  guidelines
• Strategies to improve compliance

3
Background / Prevalence of VTE

• PE is responsible for up to 200K deaths per year
  in the United States¹
• PE remains the most common preventable cause of
  hospital death, accounting for up to 10²
• DVT/PE is much more common in the hospitalized
  patient -- medical and surgical³
• 1. Horlander, KT, Mannino, DM, Leeper, KV. Arch
  Intern Med 2003 1631711
• 2. Pendleton R et al. Am J Hemat.
  200579229-237.
• 3. Edelsberg J et al. Am J Health Syst Pharm
  2006 63 16S-22S

4
Background / Prevalence

• VTE is more than 130 times greater among
  hospitalized patients than community residents¹
• half of community-based cases nursing home
  patients or within 90 days of hospital discharge
• 60 of all cases occurred in either hospitalized,
  recently d/cd, or NH patients!
• Hospitalization for acute medical illness is
  associated with up to an 8-fold increase in
  relative risk for VTE
• 1. Heit, JA, Melton, LJ, Lohse, CM, et al. Mayo
  Clin Proc 2001 76 1102

5
Background / Prevalence

• Death occurs in about 6 of DVT cases within one
  month of diagnosis1
• Death occurs in about 12 of PE cases within one
  month of diagnosis1
• Up to 25 of distal DVT can propagate into
  proximal DVT²
• Pulmonary emboli are detected in approximately
  50 of patients with proximal DVT²
• Recurrent DVT
• Can occur in 30 of DVT patients within 10 years
  after initial treatment³
• 1. American Heart Association. Heart Disease and
  Stroke Statistics 2005 Update.
• 2. Anand, SA et al. JAMA. 19982791094-1099.
• 3. Prandoni P et al. Haemotologia 2007 92
  199-205

6
Background / Prevalence¹

• Without prophylaxis, overall DVT incidence in
  hospitalized medical and general surgical
  patients is 10-40
• 40-60 following major orthopedic surgery
• Without prophylaxis, fatal PE occurs with the
  following frequency in hospitalized patients
• 0.1-0.8 undergoing elective general surgery
• 2-3 undergoing elective hip replacement
• 4-7 undergoing surgery for fractured hip!
• 1. Geerts WH et al. Chest. 2004126(3
  suppl)338S-400S

7
Background / Prevalence

• Without prophylaxis, reported VTE occurrence in
  the ICU ranges between lt10 to nearly 100!!
• Virtually all critical care patients are at
  moderate to high risk
• Up to 10 to 15 of patients with cancer may
  develop a VTE1
• Malignancy independent factor for decreased early
  and late survival after VTE event²
• 1. Viale PH, Schwartz RN. Clin J Onco Nurs.
  20048455-461.
• 2. Heit JA et al. Arch Intern Med.
  1999159445-453

8
Consequences of Unprevented VTE

• Fatal PE -- usually occurs without warning and
  often with no potential to resuscitate¹
• Patient discomfort associated with VTE
• Initial pain and discomfort
• Post-thrombotic syndrome (PTS)²
• Chronic Thromboembolic Pulmonary Hypertension
  (CTPH)³
• spent in the investigation of suspected and
  treatment of documented VTE
• Risk of treatment once VTE occurs
• Increased length of initial hospital stay
• More frequent hospital readmission
• Increased future risk of VTE (4)
• 1. Anderson FA et al. Arch Intern Med 1991 151
  933-8
• 2. Büller, HR et al. Chest. 20041264018-4288.
• 3. Pengo V et al. N EnglJ Med. 20043502257-2264.
  
• 4. Heit JA et al. Arch Intern Med 2000 160761-8

9
Benefits / Rationale of VTE Prophylaxis

• DVT and PE are prevalent and serious
  complications1
• Difficult to predict with any certainty which
  patients will develop VTE²
• Patients can experience VTE weeks after surgery2
• Clinical consequences of VTE, including
  mortality, are common3
• Health burden associated with VTE is expected to
  grow dramatically during coming years, in part
  due to aging population (4)
• 1. Geerts WH et al. Chest. 2004126(3
  suppl)338S-400S.
• 2. White RH et al. Arch Intern Med.
  19981581525-1531.
• 3. Pengo V et al. N Engl J Med.
  20043502257-2264.
• 4. Stein PQ et al. Arch Intern Med 2004.
  1642260-65

10
Benefits / Rationale of VTE Prophylaxis¹

• Hospital-acquired DVT/PE is usually clinically
  silent --only 1/3 present with classic symptoms²
• Overall incidence likely underestimated³
• Screening, either by physical exam or noninvasive
  testing, is not clinically effective or cost
  effective
• Prophylaxis is far more effective for preventing
  death/morbidity from VTE than is treatment of
  established disease
• 1. Geerts WH et al. Chest. 2004126(3
  suppl)338S-400S
• 2. Turkstra F et al. Ann Intern Med 1997 126
  775-81
• 3. Kyrle PA et al. Lancet 2005 365 1163-74

11
Benefits / Rationale of VTE prophylaxis

• Effective and safe prophylactic measures are
  available for most high-risk patients (1,2)
• pharmacologic prophylaxis lowers the risk of
  symptomatic and asymptomatic VTE in medical
  patients by 50-75!
• little or no increase in rates of clinically
  important bleeding complications
• Based on solid principles and scientific evidence
  from large numbers of randomized clinical trials³
• Most hospitalized patients have one or more risk
  factor for VTE and importantly, these are
  cumulative(4)
• 1. Gerotziafas, GT, Samama, MM. Curr Opin Pulm
  Med 2004 10356
• 2. Clagett, GP, Reisch, JS. Ann Surg 1988
  208227
• 3. Patel R et al. J Crit Care 2005 2034-7
• 4. Dorfman, et al. J Clin Pharm Therap 2006 31
  455-9

12
Benefits of VTE Prophylaxis

• Appropriate VTE prophylaxis achieves two very
  desirable results
• Improved patient outcomes
• Reduced costs

13
Risk Factors Predicting VTE

• No definitive way to predict which patients will
  acquire VTE1
• Risk factors for VTE have been reported1,2
• Preexisting and surgical risk factors for VTE can
  be cumulative for patients undergoing surgery3
• Patients undergoing hip or knee replacement or
  hip fracture surgery are among those at highest
  risk1

1. Geerts WH et al. Chest. 2004126(3
suppl)338S-400S. 2. Heit JA et al Arch Intern
Med. 2000160809-815. 3. Geerts WH, et al.
Chest. 2001119132S-175S.
14
VTE Risk Medical and Surgical Patient
Characteristics (1,2)

• History of VTE
• Family history VTE
• Malignancy
• Increased age (possibly 41)
• CHF
• AMI
• Ischemic CVA
• Pregnancy/Postpartum
• Infection/Sepsis
• Prolonged immobilization
• Acute/chronic lung disease
• Hypotension/shock

• Inflammatory disease (including IBD)
• Estrogen therapy
• Obesity (BMIgt25)
• Tobacco use
• Varicose veins
• Inhibitor deficiency states
• Antiphospholipid Abs
• Protein C/S
• Factor V Leiden (3-7)
• Prothrombin Gene Mutation (2)
• AT III

1. Geerts WH et al. Chest. 2004126(3
suppl)338S-400S Heit JA et al. Arch Intern Med.
2000160809-815. 2. Kikura, M, Takada, T, Sato,
S. Preexisting morbidity as an independent risk
factor for perioperative acute
thromboembolism syndrome. Arch Surg 2005
1401210
15
Surgical Risk Factors

• Procedure
• Surgical site
• Surgical technique
• Anesthetic
• Duration of procedure
• Presence of infection
• Postoperative immobilization

16
Virchows Triad¹

• Vascular Injury²
• Recurrent DVT/PE
• Surgery
• Cancer treatment
• Trauma
• Venipuncture
• Atherosclerosis
• IV drug administration

Venous Stasis² Obesity Immobility Chronic heart
disease Age above 40
Hypercoaguable State2 Hereditary risk
factors Bleeding disorders Malignancy
Risk Factors are Cumulative3
1. Anderson, FA et al. Circulation.2003107I-9--I
-10. 2. Viale PH, Schwartz RN. Clin J Onco Nurs.
20048455-461. 3. Rosendaal FR. Lancet.
19993531167-1173.
17
Extended VTE Risk Following Hospital Discharge

• VTE can occur for up to 3 months after total knee
  and hip arthroplasty1
• Hypercoagulability can persist for 6 weeks after
  hip fracture2
• Venous function was significantly impaired for up
  to 42 days following hip fracture surgery3
• Recurrent DVT
• 30 of DVT patients 8 to 10 years after initial
  treatment4

1. White RH et al. Arch Intern Med.
19981581525-1531. 2. Wilson D et al. Injury.
200132765-770. 3. Wilson D et al. Injury.
20023333-39. 4. American Heart Association.
Heart Disease and Stroke Statistics 2005 Update.
18
Features of an Ideal VTE Prophylaxis Regimen

• Effective
• Safe
• Good compliance
• Easily administered
• No laboratory monitoring needed
• Cost effective

19
Methods of VTE Prophylaxis

• Mechanical
• Graduated Compression Stockings (GCS)
• Intermittent Pneumatic Compression Devices (IPC)
• Pharmacologic

20
Mechanical Prophylaxis

• Disadvantages
• No mechanical prophylaxis options have been shown
  to reduce the risk of death or PE1
• Must be worn continuously pre-, intra- and
  postoperatively for 72 hours1
• GCS can cause impairment in tissue oxygenation
  (PVD)3
• GCS need to be sized and fitted properly3

• Advantages
• Lack of bleeding potential1
• No clinically important side effects
• No laboratory monitoring needed2
• IPC stimulates endogenous fibrinolytic activity
  (reduces plasminogen activator inhibitor-1 levels
  by unknown mechanism) 2

1. Geerts WH et al. Chest. 2004126(3
suppl)338S-400S. 2. Davis P. J Ortho Nurs.
2004850-56. 3. Agu O et al. Br J Surg.
199986992-1004.
21
Pharmacologic Prophylaxis

• Aspirin NOT recommended as sole prophylaxis
  agent1
• Low-dose unfractionated heparin (LDUH)2
• Low molecular weight heparin (LMWH)2
• Enoxaparin
• Dalteparin
• Tinzaparin
• Vitamin K antagonist (VKA)1
• Warfarin
• Factor Xa inhibitor2
• Fondaparinux

Choice of pharmacologic agent depends on VTE risk
reduction, complication rate and proper dosing of
agent2
1. Geerts WH et al. Chest. 2004126(3
suppl)338S-400S. 2. Pendleton R et al. Am J
Hemat. 200579229-237.
22
Risky Business

• The majority of hospitalized medical and surgical
  patients are at increased risk of VTE²
• Risks appear to be cumulative¹
• Risk stratification is cumbersome, not adequately
  validated, and therefore not as widely
  agreed-upon in medical patients as in surgical
  patients
• Guidelines, however, do exist (2,3)
• 1. Dorfman, et al. J Clin Pharm Therap 2006 31
  455-9
• 2. Edelsberg, J et al. Am J Health-Syst Pharm
  2006. 63 S16-S22
• 3. Geerts WH et al. Chest. 2004126(3
  suppl)338S-400S.

23
ACCP Recommendations (since 1986)

• Geerts, WH, et al. CHEST 2004 126 338s-400s

24
VTE Prophylaxis Usage

• Varies markedly, overall remaining abysmally low
• Audit of 384 patients with VTE¹
• 201 (52) received prophylaxis (112
  anticoagulation, 31 mechanical prophylaxis, 58
  combination)
• 183 (48) No prophylaxis
• 13 deaths due to PE
• One study showed that only 46 of hospitalized
  medical patients, with risk factors for VTE,
  received appropriate prophylaxis²
• Various studies show a VTE prophylaxis rate in
  surgical patients varying from 38 to 94 (3,4)
• true even amongst orthopedic surgeons³
• 1. Goldhaber et al. Chest 20001181680-1684.
• 2. Ageno et al. Haematologia 2002 87 746-50
• 3. Stratton et al. Arch Intern Med 2000 160
  334-40
• 4.Anderson et al. J Thromb Thrombol 1998 5
  S7-S11

25
VTE Prophylaxis Usage

• Even when used, guideline recommendations often
  not followed
• Grade IA ACCP recommendations were followed from
  45 (hip fracture surgery) to 84 (elective THR)
  of the time¹
• Retrospective study overall compliance rate
  13.3 in greater than 120,000 hospital
  admissions²
• 2.8 Neurosurgery
• 52.4 Orthopedic Surgery
• 13.3 Medicine
• 1. Statton et al. Arch Intern Med 2000 160
  334-40
• 2. Yu HT et al. Am J Health Syst Pharm 2007. 64
  69-76

26
VTE Prophylaxis Usage

• Hospitalists found superior!¹
• Pneumonia Care VTE prophylaxis
• 96.0 vs. 61.9
• 1. William D et al. Am J Manag Care 2007.
  13129-32

27
Contributing Factors to Under Use Physician
Related (1,2)

• Lack of awareness / unfamiliarity with guidelines
• Perception that VTE is not a significant or
  frequent problem
• Patients will be ambulatory soon enough
• Concern over bleeding risks (surgical sites and
  elsewhere)
• Guidelines seem complicated or difficult to apply
• Patients so ill on admission that VTE concerns
  dont hit the radar screen
• More difficult to change habits than to
  incorporate a new habit
• 1. Geerts et al. Chest 2004 126 338S-400S
• 2. Cabana et al. JAMA 1999 282 1458-65

28
Contributing Factors to Under use --
Environmental¹

• Not under physicians direct control, such as
  acquisition of new resources or facilities
• Lack of time
• Financial constraints (increased practice costs,
  lack of reimbursement)
• Increased legal liability
• 1. Cabana et al. JAMA 1999 282 1458-65

29
Contributing Factors to Under Use Institution
Related¹

• Lack of standardized order sets for VTE
  prophylaxis
• Lack of user-friendly patient risk assessment
  tools/mechanisms
• Logistical limitations of health care management
  systems, for instance lack of medical informatics
  systems with computerized prompts
• 1. Cabana et al. JAMA 1999 282 1458-65

30
National Consensus Standards for Prevention and
Care of VTE

• JCAHO and National Quality Forum (NQF) -- project
  began 9/04
• Eight different measures have been recommended by
  the Technical Advisory Panel (TAP) for pilot
  testing this year. Regarding VTE prophylaxis,
  these include
• VTE Risk Assessment (RA)/Prophylaxis within 24
  hours of hospital admission
• VTE Risk Assessment (RA)/Prophylaxis within 24
  hours of transfer to ICU
• Incidence of Potentially Preventable
  Hospital-acquired VTE

31
Center for Medicare and Medicaid Services

• CMS is strongly considering using VTE prophylaxis
  as a core safety compliance and performance
  measure
• This will directly affect hospital / physician
  reimbursements (i.e., pay for performance)

32
The Literature What Has Worked?

• Respected leaders within institutions¹
• Clinical audits with feedback (2,3)
• Clinical decision support tools (83 ? 95) (4)
• Clinical guidelines combined with chart
  monitoring (5)
• Nursing/patient education for increased
  compliance with SCDs (6)
• Establishment of protocols, combined with staff
  education and a daily computer driven reminder
  (reporting tool) for morning rounds in ICU (7)
• Computer based reminders (8)
• 1. Winkler, et al. Arch Intern Med 1985
  145314-7
• 2. Williams, et al. Ann R Coll Surg Engl 1997
  7955-7
• 3. Greco, et al. NEJM 1993 329 1271-4
• 4. Durieux, et al. JAMA 2000 283 2816-21
• 5. Phillips, et al. Thromb Haemost 1997 77
  283-8
• 6. Stewart, D et al. Ann Surg 2006. 72 921-3
• 7. Wahl, WL et al. Surgery 2006. 140 648-9
• 8. Patterson R. Proc AMIA Symp 1998. 573-6

33
Future Directions -- UCHSC

• Increase overall VTE prophylaxis compliance
• Improved methods of risk stratification
• Increased adherence to established guidelines
• Proposed results
• Improved patient safety and outcomes
• Improved adherence to JHACO / CMS standards and
  institutionally established compliance
  targets/goals

34
Proposed Study - UCHSC

• Prospective historical controlled trial
• Develop simple, useable method of VTE risk
  stratification
• Utilize prompts written and eventually
  electronic
• Measure compliance rates compared to historic
  rates

35
Methods

• Using established risk factors, develop simple,
  useable method of risk stratifications for
  clinicians, using methods that have proved
  effective¹
• Initially paper admission/transfer orders
• With CPOE, add as pop-up²
• Include current ACCP guidelines
• Use medication reconciliation sheets/orders as
  reminder
• Forms would be mandatory for all
  admissions/transfers
• Again, with CPOE, would be contained therein
• Measure rates of physician compliance and choice
  of method on high-risk patients (2 or more risk
  factors) pre and post implementation
• 1. McCaffrey R et al. Worldviews Evid Based Nurs
  2007 414-20
• 2. Paterno MD et al. AMIA Annu Symp Proc 2006
  1058

36
General Conclusions

• VTE prophylaxis is justified, low-risk, and
  indicated in most hospitalized patients
• Good for patients
• Good for hospitals
• Overall, VTE prophylaxis is under-utilized
• Hospitals and physicians will soon be judged on
  compliance
• Each hospital needs a standardized approach for
  VTE prophylaxis to improve compliance
• protocols, pre-printed orders, risk
  stratification, etc.
• Multi-disciplinary approach
• auditing

37
Thanks