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

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

Background / Prevalence of VTE PE is responsible for up to 200K deaths per year in the United States¹ 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 10%² PE remains the most common preventable cause of hospital death, accounting for up to 10%² DVT/PE is much more common in the hospitalized patient -- medical and surgical³ DVT/PE is much more common in the hospitalized patient -- medical and surgical³ 1. Horlander, KT, Mannino, DM, Leeper, KV. Arch Intern Med 2003; 163: Pendleton R et al. Am J Hemat. 2005;79: Edelsberg J et al. Am J Health Syst Pharm 2006; 63: 16S-22S

Background / Prevalence VTE is more than 130 times greater among hospitalized patients than community residents¹ 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 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/c’d, or NH patients! 60% of all cases occurred in either hospitalized, recently d/c’d, or NH patients! Hospitalization for acute medical illness is associated with up to an 8-fold increase in relative risk for VTE 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

Background / Prevalence Death occurs in about 6% of DVT cases within one month of diagnosis 1 Death occurs in about 6% of DVT cases within one month of diagnosis 1 Death occurs in about 12% of PE cases within one month of diagnosis 1 Death occurs in about 12% of PE cases within one month of diagnosis 1 Up to 25% of distal DVT can propagate into proximal DVT² Up to 25% of distal DVT can propagate into proximal DVT² Pulmonary emboli are detected in approximately 50% of patients with proximal DVT² Pulmonary emboli are detected in approximately 50% of patients with proximal DVT² Recurrent DVT: Recurrent DVT: Can occur in 30% of DVT patients within 10 years after initial treatment³ 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. 1998;279: Prandoni P et al. Haemotologia 2007; 92:

Background / Prevalence¹ Without prophylaxis, overall DVT incidence in hospitalized medical and general surgical patients is 10-40% Without prophylaxis, overall DVT incidence in hospitalized medical and general surgical patients is 10-40% 40-60% following major orthopedic surgery 40-60% following major orthopedic surgery Without prophylaxis, fatal PE occurs with the following frequency in hospitalized patients: Without prophylaxis, fatal PE occurs with the following frequency in hospitalized patients: % undergoing elective general surgery % undergoing elective general surgery 2-3% undergoing elective hip replacement 2-3% undergoing elective hip replacement 4-7% undergoing surgery for fractured hip! 4-7% undergoing surgery for fractured hip! Geerts WH et al. Chest. 2004;126(3 suppl):338S-400S

Background / Prevalence Without prophylaxis, reported VTE occurrence in the ICU ranges between <10% to nearly 100%!! Without prophylaxis, reported VTE occurrence in the ICU ranges between <10% to nearly 100%!! Virtually all critical care patients are at moderate to high risk Virtually all critical care patients are at moderate to high risk Up to 10% to 15% of patients with cancer may develop a VTE 1 Up to 10% to 15% of patients with cancer may develop a VTE 1 Malignancy independent factor for decreased early and late survival after VTE event² Malignancy independent factor for decreased early and late survival after VTE event² 1. Viale PH, Schwartz RN. Clin J Onco Nurs. 2004;8: Heit JA et al. Arch Intern Med. 1999;159:

Consequences of Unprevented VTE Fatal PE -- usually occurs without warning and often with no potential to resuscitate¹ Fatal PE -- usually occurs without warning and often with no potential to resuscitate¹ Patient discomfort associated with VTE Patient discomfort associated with VTE Initial pain and discomfort Initial pain and discomfort Post-thrombotic syndrome (PTS)² Post-thrombotic syndrome (PTS)² Chronic Thromboembolic Pulmonary Hypertension (CTPH)³ Chronic Thromboembolic Pulmonary Hypertension (CTPH)³ $$ spent in the investigation of suspected and treatment of documented VTE $$ spent in the investigation of suspected and treatment of documented VTE Risk of treatment once VTE occurs Risk of treatment once VTE occurs Increased length of initial hospital stay Increased length of initial hospital stay More frequent hospital readmission More frequent hospital readmission Increased future risk of VTE (4) Increased future risk of VTE (4) 1. Anderson FA et al. Arch Intern Med 1991; 151: Büller, HR et al. Chest. 2004;126: Pengo V et al. N EnglJ Med. 2004;350: Heit JA et al. Arch Intern Med 2000; 160:761-8

Benefits / Rationale of VTE Prophylaxis DVT and PE are prevalent and serious complications 1 DVT and PE are prevalent and serious complications 1 Difficult to predict with any certainty which patients will develop VTE² Difficult to predict with any certainty which patients will develop VTE² Patients can experience VTE weeks after surgery 2 Patients can experience VTE weeks after surgery 2 Clinical consequences of VTE, including mortality, are common 3 Clinical consequences of VTE, including mortality, are common 3 Health burden associated with VTE is expected to grow dramatically during coming years, in part due to aging population (4) Health burden associated with VTE is expected to grow dramatically during coming years, in part due to aging population (4) Geerts WH et al. Chest. 2004;126(3 suppl):338S-400S. 2. White RH et al. Arch Intern Med. 1998;158: Pengo V et al. N Engl J Med. 2004;350: Stein PQ et al. Arch Intern Med :

Benefits / Rationale of VTE Prophylaxis¹ Hospital-acquired DVT/PE is usually clinically silent -- only 1/3 present with classic symptoms² Hospital-acquired DVT/PE is usually clinically silent -- only 1/3 present with classic symptoms² Overall incidence likely underestimated³ Overall incidence likely underestimated³ Screening, either by physical exam or noninvasive testing, is not clinically effective or cost effective 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 Prophylaxis is far more effective for preventing death/morbidity from VTE than is treatment of established disease 1. Geerts WH et al. Chest. 2004;126(3 suppl):338S-400S 2. Turkstra F et al. Ann Intern Med 1997; 126: Kyrle PA et al. Lancet 2005; 365:

Benefits / Rationale of VTE prophylaxis Effective and safe prophylactic measures are available for most high-risk patients (1,2) 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%! 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 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 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) 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; 10: Clagett, GP, Reisch, JS. Ann Surg 1988; 208: Patel R et al. J Crit Care 2005; 20: Dorfman, et al. J Clin Pharm Therap 2006; 31: 455-9

Benefits of VTE Prophylaxis Appropriate VTE prophylaxis achieves two very desirable results: Appropriate VTE prophylaxis achieves two very desirable results: Improved patient outcomes Improved patient outcomes Reduced costs Reduced costs

No definitive way to predict which patients will acquire VTE 1 No definitive way to predict which patients will acquire VTE 1 Risk factors for VTE have been reported 1,2 Risk factors for VTE have been reported 1,2 Preexisting and surgical risk factors for VTE can be cumulative for patients undergoing surgery 3 Preexisting and surgical risk factors for VTE can be cumulative for patients undergoing surgery 3 Patients undergoing hip or knee replacement or hip fracture surgery are among those at highest risk 1 Patients undergoing hip or knee replacement or hip fracture surgery are among those at highest risk 1 1. Geerts WH et al. Chest. 2004;126(3 suppl):338S-400S. 2. Heit JA et al Arch Intern Med. 2000;160: Geerts WH, et al. Chest. 2001;119:132S-175S. Risk Factors: Predicting VTE

VTE Risk: Medical and Surgical Patient Characteristics (1,2) History of VTE History of VTE Family history VTE Family history VTE Malignancy Malignancy Increased age (possibly ≥ 41) Increased age (possibly ≥ 41) CHF CHF AMI AMI Ischemic CVA Ischemic CVA Pregnancy/Postpartum Pregnancy/Postpartum Infection/Sepsis Infection/Sepsis Prolonged immobilization Prolonged immobilization Acute/chronic lung disease Acute/chronic lung disease Hypotension/shock Hypotension/shock Inflammatory disease (including IBD) Estrogen therapy Obesity (BMI>25) Tobacco use Varicose veins Inhibitor deficiency states Antiphospholipid Ab’s Protein C/S Factor V Leiden (3-7%) Prothrombin Gene Mutation (2%) AT III 1. Geerts WH et al. Chest. 2004;126(3 suppl):338S-400S; Heit JA et al. Arch Intern Med. 2000;160: Kikura, M, Takada, T, Sato, S. Preexisting morbidity as an independent risk factor for perioperative acute thromboembolism syndrome. Arch Surg 2005; 140:1210 thromboembolism syndrome. Arch Surg 2005; 140:1210

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

Virchow’s Triad ¹ Vascular Injury ² Recurrent DVT/PE Surgery Cancer treatment TraumaVenipunctureAtherosclerosis IV drug administration Risk Factors are Cumulative 3 1. Anderson, FA et al. Circulation.2003;107:I-9--I Viale PH, Schwartz RN. Clin J Onco Nurs. 2004;8: Rosendaal FR. Lancet. 1999;353: Hypercoaguable State 2 Hereditary risk factors Bleeding disorders Malignancy Venous Stasis ² Obesity Immobility Chronic heart disease Age above 40

Extended VTE Risk Following Hospital Discharge VTE can occur for up to 3 months after total knee and hip arthroplasty 1 VTE can occur for up to 3 months after total knee and hip arthroplasty 1 Hypercoagulability can persist for 6 weeks after hip fracture 2 Hypercoagulability can persist for 6 weeks after hip fracture 2 Venous function was significantly impaired for up to 42 days following hip fracture surgery 3 Venous function was significantly impaired for up to 42 days following hip fracture surgery 3 Recurrent DVT: Recurrent DVT: 30% of DVT patients 8 to 10 years after initial treatment 4 30% of DVT patients 8 to 10 years after initial treatment 4 1. White RH et al. Arch Intern Med. 1998;158: Wilson D et al. Injury. 2001;32: Wilson D et al. Injury. 2002;33: American Heart Association. Heart Disease and Stroke Statistics – 2005 Update.

Features of an Ideal VTE Prophylaxis Regimen Effective Effective Safe Safe Good compliance Good compliance Easily administered Easily administered No laboratory monitoring needed No laboratory monitoring needed Cost effective Cost effective

Methods of VTE Prophylaxis Mechanical: Mechanical: Graduated Compression Stockings (GCS) Graduated Compression Stockings (GCS) Intermittent Pneumatic Compression Devices (IPC) Intermittent Pneumatic Compression Devices (IPC) Pharmacologic Pharmacologic

Mechanical Prophylaxis Advantages Lack of bleeding potential 1 Lack of bleeding potential 1 No clinically important side effects No clinically important side effects No laboratory monitoring needed 2 No laboratory monitoring needed 2 IPC stimulates endogenous fibrinolytic activity (r educes plasminogen activator inhibitor-1 levels by unknown mechanism) 2 IPC stimulates endogenous fibrinolytic activity (r educes plasminogen activator inhibitor-1 levels by unknown mechanism) 2 Disadvantages No mechanical prophylaxis options have been shown to reduce the risk of death or PE 1 Must be worn continuously: pre-, intra- and postoperatively for 72 hours 1 GCS can cause impairment in tissue oxygenation (PVD) 3 GCS need to be sized and fitted properly 3 1. Geerts WH et al. Chest. 2004;126(3 suppl):338S-400S. 2. Davis P. J Ortho Nurs. 2004;8: Agu O et al. Br J Surg. 1999;86:

Pharmacologic Prophylaxis Aspirin – NOT recommended as sole prophylaxis agent 1 Low-dose unfractionated heparin (LDUH) 2 Low molecular weight heparin (LMWH) 2 Enoxaparin Dalteparin Tinzaparin Vitamin K antagonist (VKA) 1 Warfarin Factor Xa inhibitor 2 Fondaparinux Choice of pharmacologic agent depends on VTE risk reduction, complication rate and proper dosing of agent 2 1. Geerts WH et al. Chest. 2004;126(3 suppl):338S-400S. 2. Pendleton R et al. Am J Hemat. 2005;79:

Risky Business The majority of hospitalized medical and surgical patients are at increased risk of VTE² The majority of hospitalized medical and surgical patients are at increased risk of VTE² Risks appear to be cumulative¹ 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 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) Guidelines, however, do exist (2,3) 1. Dorfman, et al. J Clin Pharm Therap 2006; 31: Edelsberg, J et al. Am J Health-Syst Pharm : S16-S22 3. Geerts WH et al. Chest. 2004;126(3 suppl):338S-400S.

ACCP Recommendations (since 1986) Geerts, WH, et al. CHEST 2004; 126: 338s-400s Geerts, WH, et al. CHEST 2004; 126: 338s-400s

VTE Prophylaxis Usage Varies markedly, overall remaining abysmally low Varies markedly, overall remaining abysmally low Audit of 384 patients with VTE¹: Audit of 384 patients with VTE¹: 201 (52%) received prophylaxis (112 anticoagulation, 31 mechanical prophylaxis, 58 combination) 201 (52%) received prophylaxis (112 anticoagulation, 31 mechanical prophylaxis, 58 combination) 183 (48%) No prophylaxis 183 (48%) No prophylaxis 13 deaths due to PE 13 deaths due to PE One study showed that only 46% of hospitalized medical patients, with risk factors for VTE, received appropriate prophylaxis² 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) Various studies show a VTE prophylaxis rate in surgical patients varying from 38% to 94% (3,4) true even amongst orthopedic surgeons³ true even amongst orthopedic surgeons³ 1. Goldhaber et al. Chest 2000:118: Ageno et al. Haematologia 2002; 87: Stratton et al. Arch Intern Med 2000; 160: Anderson et al. J Thromb Thrombol 1998; 5: S7-S11

VTE Prophylaxis Usage Even when used, guideline recommendations often not followed 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 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 Retrospective study – overall compliance rate 13.3% in greater than 120,000 hospital admissions² 2.8% Neurosurgery 2.8% Neurosurgery 52.4 % Orthopedic Surgery 52.4 % Orthopedic Surgery 13.3 % Medicine 13.3 % Medicine 1. Statton et al. Arch Intern Med 2000; 160: Yu HT et al. Am J Health Syst Pharm : 69-76

VTE Prophylaxis Usage Hospitalists found superior!¹ Hospitalists found superior!¹ Pneumonia Care + VTE prophylaxis Pneumonia Care + VTE prophylaxis 96.0% vs. 61.9% 96.0% vs. 61.9% 1. William D et al. Am J Manag Care :129-32

Contributing Factors to Under Use – Physician Related (1,2) Lack of awareness / unfamiliarity with guidelines Lack of awareness / unfamiliarity with guidelines Perception that VTE is not a significant or frequent problem Perception that VTE is not a significant or frequent problem Patients will be ambulatory “soon enough” Patients will be ambulatory “soon enough” Concern over bleeding risks (surgical sites and elsewhere) Concern over bleeding risks (surgical sites and elsewhere) Guidelines seem complicated or difficult to apply Guidelines seem complicated or difficult to apply Patients so ill on admission that VTE concerns don’t “hit the radar screen” Patients so ill on admission that VTE concerns don’t “hit the radar screen” More difficult to change habits than to incorporate a new habit 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:

Contributing Factors to Under use -- Environmental¹ Not under physicians’ direct control, such as acquisition of new resources or facilities Not under physicians’ direct control, such as acquisition of new resources or facilities Lack of time Lack of time Financial constraints (increased practice costs, lack of reimbursement) Financial constraints (increased practice costs, lack of reimbursement) Increased legal liability Increased legal liability 1. Cabana et al. JAMA 1999; 282: Cabana et al. JAMA 1999; 282:

Contributing Factors to Under Use – Institution Related¹ Lack of standardized order sets for VTE prophylaxis Lack of standardized order sets for VTE prophylaxis Lack of user-friendly patient risk assessment tools/mechanisms 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” Logistical limitations of health care management systems, for instance lack of medical informatics systems with computerized “prompts” 1. Cabana et al. JAMA 1999; 282:

National Consensus Standards for Prevention and Care of VTE JCAHO and National Quality Forum (NQF) -- project began 9/04 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: 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 hospital admission VTE Risk Assessment (RA)/Prophylaxis within 24 hours of transfer to ICU VTE Risk Assessment (RA)/Prophylaxis within 24 hours of transfer to ICU Incidence of Potentially Preventable Hospital-acquired VTE Incidence of Potentially Preventable Hospital-acquired VTE

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

The Literature – What Has Worked? Respected leaders within institutions¹ Respected leaders within institutions¹ Clinical audits with feedback (2,3) Clinical audits with feedback (2,3) Clinical decision support tools (83% → 95%) (4) Clinical decision support tools (83% → 95%) (4) Clinical guidelines combined with chart monitoring (5) Clinical guidelines combined with chart monitoring (5) Nursing/patient education for increased compliance with SCD’s (6) Nursing/patient education for increased compliance with SCD’s (6) Establishment of protocols, combined with staff education and a daily computer driven reminder (reporting tool) for morning rounds in ICU (7) 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) Computer based reminders (8) 1. Winkler, et al. Arch Intern Med 1985; 145: Williams, et al. Ann R Coll Surg Engl 1997; 79: Greco, et al. NEJM 1993; 329: Durieux, et al. JAMA 2000; 283: Phillips, et al. Thromb Haemost 1997; 77: Stewart, D et al. Ann Surg : Wahl, WL et al. Surgery : Patterson R. Proc AMIA Symp

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

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

Methods Using established risk factors, develop simple, useable method of risk stratifications for clinicians, using methods that have proved effective¹ Using established risk factors, develop simple, useable method of risk stratifications for clinicians, using methods that have proved effective¹ Initially paper admission/transfer orders Initially paper admission/transfer orders With CPOE, add as “pop-up”² With CPOE, add as “pop-up”² Include current ACCP guidelines Include current ACCP guidelines Use medication reconciliation sheets/orders as reminder Use medication reconciliation sheets/orders as reminder Forms would be mandatory for all admissions/transfers Forms would be mandatory for all admissions/transfers Again, with CPOE, would be contained therein 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 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; 4: Paterno MD et al. AMIA Annu Symp Proc 2006; 1058

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

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