1. Medical Patients – VTE Prevention Dale W. Bratzler, DO, MPH Professor and Associate Dean, College of Public Health Professor of Medicine, College of Medicine Chief Quality Officer – OU Physicians Group University of Oklahoma Health Sciences Center August 3, 2012

3. During 2007–2009, an estimated annual average of 547,596 adult hospitalizations occurred for which a discharge diagnosis of VTE was recorded; 348,558 of these hospitalizations had a discharge diagnosis of DVT, and 277,549 had a discharge diagnosis of PE. A total of 78,511 had both discharge diagnoses. MMWR. 2012; 61:401-4.

4. VTE in Medical Patients  Medical patients account for: - 80% of fatal PE in hospitals - 60% of symptomatic VTE in hospitals  No prophylaxis + routine screening for DVT: DVT 10-20% (greater in stroke) Proximal DVT 4-5%

5. Burden of VTE in Hospital Patients Why are medical patients so important? VTE risk per patient Examples: SCI THR, TKR other surgery medical patients maj trauma 100% 25% 75% 50%

6. ACP Meta-Analysis of VTE Prophylaxis in Medical Patients: Summary 1.In medical patients, anticoagulant prophylaxis reduced PE but not total mortality or symptomatic DVT with more bleeding events (but not more major bleeding). 2.In acute stroke patients, anticoagulant prophylaxis did not reduce total mortality, PE or symptomatic DVT but increased major bleeding (but not all bleeding). 3.In medical + acute stroke patients, anticoagulant prophylaxis reduced PE but not total mortality (p=0.056) or symptomatic DVT with increased major and all bleeding. 4.No difference in any outcomes for LDH vs LMWH. Lederle – Ann Intern Med 2011;155:602

7. ACP VTE Prophylaxis in Medical Patients: Recommendations 1.Assess risk of VTE and bleeding before starting prophylaxis i.e. individual risk assessment [strong recommendation; moderate quality evidence] 2.Use anticoagulant prophylaxis (heparin, LMWH, fonda) unless bleeding risk outweighs likely benefit [strong recommendation; moderate quality evidence] 3.Don’t use graduated compression stockings [strong recommendation; moderate quality evidence] 4.ACP does not support use of performance measures in medical patients that promote universal prophylaxis regardless of risk Qaseem – Ann Intern Med 2011;155:625

8. ACP Meta-Analysis of VTE Prophylaxis in Medical Patients: Limitations -1 1.Asked a question for which the answer was already known (Lederle, 1998, 2006; Dentali 2007; Wein 2007; etc). 2.Combined very different patient groups (GIM, ICU, ischemic stroke, palliative care) to get greater power BUT… 3.Expanding the sample increases heterogeneity not truth. 4.More than ½ of the included studies used prophylaxis options (agent or dose) we don’t use (17/32 trials). 5.Many studies followed patients for only 7-30 days. Lederle – Ann Intern Med 2011;155:602

9. Symptomatic VTE in Medical Patients  Meta-analysis of RCTs of anticoagulant vs no prophylaxis  9 studies with 19,958 medical patients Outcome No prophylaxis Prophylaxis RR [95% CI] NNT PE 49/10043 20/9915 0.43 [0.26-0.71] 345 Fatal PE 39/9823 14/96870.38 [0.21-0.69] 400 Sympt DVT 21/2587 10/26190.47 [0.22-1.00] Death 165/3679 158/36760.97 [0.77-1.21] Maj Bleed 19/4304 25/43011.32 [0.73-2.37] Dentali – Ann Intern Med 2007;146:278

10. Meta-analysis of Thromboprophylaxis in Medical Patients No Prophylaxis vs Anticoagulant Prophylaxis No Rel Outcome Trials Patients Prophy Prophy Risk p DVT 22 8,333 11.0% > 4.9% 0.45 <0.001 PE 19 39,762 1.0% > 0.6% 0.48 <0.001 Mortality 20 42,960 7.5% 7.3% 0.95 0.15 Bleeding 16 40,031 1.7% < 3.8% 1.71 <0.001 Wein – Arch Intern Med 2007;167:1476

11. Meta-analysis of Thromboprophylaxis in Medical Patients Low Dose Heparin vs Low Molecular Weight Heparin Outcome Trials Patients LDH LMWH Rel Risk p DVT 9 4,421 5.4% > 3.7% 0.68 0.004 PE 7 4,231 0.6% 0.3% 0.65 0.36 Mortality 10 4,881 2.9% 3.3% 1.14 0.46 Total Bldg 9 4,715 3.3% 2.7% 0.83 0.26 Major Bldg 7 4,497 1.8% 1.4% 0.78 0.29  platelets 3 2,574 0.5% 0.1% 0.29 0.13 Wein – Arch Intern Med 2007;167:1476

12. RCTs of Medical Prophylaxis with LMWH/LDH Lederle – Am J Med 2006;119:54 All-cause mortality

13. ACP Meta-Analysis of VTE Prophylaxis in Medical Patients: Limitations - 2 6. Inappropriate to use total mortality at 120 days as the primary outcome: a) Only 3/40 trials used it as the primary outcome b) 3 trials didn’t even report death as an outcome c) All-cause deaths have nothing to do with VTE d) Prophylaxis given for 5-14 days - ? relevance of all-cause death at120 days 7. Did not assess for symptomatic VTE (also problematic with the studies included). 8. Clinical VTE outcomes (symptomatic VTE, fatal PE) are underestimated in studies with a routine screening test for asymptomatic DVT. Lederle – Ann Intern Med 2011;155:602

14. 6.0 Medical Patients 6.0.1 For acutely ill medical patients admitted to hospital with congestive heart failure or severe respiratory disease, or who are confined to bed and have one or more additional risk factors, including active cancer, previous VTE, sepsis, acute neurological disease, or inflammatory bowel disease, we recommend prophylaxis with LMWH [Grade 1A], LDUH [Grade 1A], or fondaparinux [Grade 1A]. 6.0.2 For medical patients with risk factors for VTE, and in whom there is a contraindication to anticoagulant prophylaxis, we recommend the optimal use of mechanical prophylaxis with GCS or IPC [Grade 1A]. 8 th ACCP Guidelines on Antithrombotic Therapy

15. ACCP 9 th Edition General Overview For acutely ill hospitalized medical patients at increased risk of thrombosis, we recommend anticoagulant thromboprophylaxis with LMWH, LDUH, or fondaparinux (Grade 1B) – Mechanical prophylaxis (GCS or IPC) if bleeding or high risk for bleeding Similar recommendation for critically ill patients

16. Prophylaxis Use in Medical Patients 1,894 medical patients in 29 hospitals in 6 provinces Khan – Thromb Res 2007;119:145 90% Prophylaxis Prophylaxis Recommended indicated given prophylaxis 23%15% 100% 75% 50% 25% 0 Knowledge- care gap Appropriate use

17. Thromboprophylaxis in Medical Patients Acute medical illness with:  CHF  respiratory decompensation  stroke  bedrest + active cancer, prior VTE, sepsis, IBD 1.Individual decision 2.Daily reassessment Prophylaxis indicated  LMWH  Heparin 5,000 U bid (or tid) Anticoagulant prophylaxis contraindicated  mechanical prophylaxis - Grad compr stockings - Int pneumatic compr  anticoag when C/I gone No Yes

18. Is Prophylaxis Perfect? Surgery Type Cases (VTE event) N/D (%)* Controls N/D (%)* All Procedures72/116 (62.1)83/116 (71.6) Orthopedic surgery55/63 (87.3) Knee Replacement28/31 (90.3)23/25 (92.0) Hip Replacement17/20 (85.0)24/26 (92.3) General Surgery13/34 (38.2)17/31 (54.8) Urologic Surgery0/8 (0)2/7 (28.6) Thoracic Surgery2/5 (40.0)5/8 (62.5) Lower extremity amputation2/6 (33.3)4/7 (57.1) Boraecki AM, et al. Jt Comm J Qual Patient Saf. 2012; 38:348-57. *Appropriate pharmacologic prophylaxis.

19. Other Findings Underuse of prophylaxis for patients with malignancy Clinicians often failed to document reasons for lack of pharmacoprophylaxis (medicolegal issue) Some reasons documented for failure to use pharmacoprophylaxis are questionable (e.g., epidural use Higher rates of “mechanical prophylaxis only” in cases

21. Group name: Hospital Quality Share Group home page: http://groups.google.com/group/hospital-quality-share Group email address hospital-quality-share@googlegroups.com

22. dale-bratzler@ouhsc.edu