Medical Management and Risk Factor Modification SVS clinical research priorities meeting 2011

1. Medical Management and Risk Factor ModificationSVS clinical research priorities meeting 2011 Peter Henke, MD University of Michigan

2. Overview • Epidemiology of atherosclerotic/-atherothrombotic manifestations in vascular surgical patients • Current medical management of arterial vascular disease patients • Evidence for major therapies • Preoperative risk assessment pathways • Current and potential study areas/questions

3. Background Issues • Goals of medical management and risk factor modification for the vascular surgeon • Clinic setting and peri-operative setting • Local practice patterns often dictate the vascular medicine interest • Do it all yourself to consult specialists for everything • Costs saved for preventative care by vascular surgeons • Costs incurred due to multiple consultants and elaborate workups with no discernable patient benefit

4. Epidemiology • All our patients have atherosclerosis Lloyd-Jones D, etal Circulation 2010;121:e1

5. Epidemiology REACH Registry N = 64,977 with CAD, CVOD, PAD or >3 risk factors Steg PG, etal. JAMA 2007;297:1197

6. Epidemiology REACH Registry N = 68,236 with CAD, CVOD, PAD Focus on AAA patients comorbidities Baumgartner I, etal. J Vasc Surg 2008;48:808

7. Epidemiology Baumgartner I, etal. J Vasc Surg 2008;48:808

8. Epidemiology REACH Registry N = 45,227 patients with CAD, CVOD, PAD or > 3 risks 4 yr outcome Sig increased risk with DM (OR = 1.44); prior event (1.71); polyvasc Dz (1.99) Bhatt, D, etal. JAMA 2010;304:1350

9. Atherothrombotic Costs It’s expensive! AHA statistics 2010 Heidenreich PA, etal. Circ 2011;123:933

10. Strong Evidence exists for Treating our Patients • Anti-platelet therapy (ASA, IA) • Lipid mngt (LDL<100 mg/dL, IB) • HTN control (BP < 140/90 or 130/80, IB) • RAAS (IA) and B-blockers (IA) • Smoking cessation (IB) • Fitness and weight mngt (IB) Smith SC, etal. Circulation 2006;113:2363

11. Medications: ASA Meta-analysis of ASA for primary prevention N = 95,000 12% reduction in serious vascular events ATT collaboration. Lancet 2009;373:1849

12. Medications: ASA Metaanalysis of 50,279 patients with CAD for risk of events with DC Biondi-Zoccai GL, etal. Eur Heart J 2006;27:2667

13. Medications: B-blockers N= ~ 663,000 Propensity matched cohort from 329 US hospitals Major non cardiac surgery Adjusted Odds Ratio of In-hospital Mortality Associated with Beta Blocker Therapy in Major Noncardiac Surgery Stratified by Revised Cardiac Index (RCRI) Score Lindenaeur PK, et al. N Engl J Med 2005;353:349-61

14. Medications: B-blockers Bauer SM, etal. J Vasc Surg 2010;51:242

15. 40 Standard care 30 Percentage of Patients 20 P<0.001 10 Bisoprolol 0 0 7 14 21 28 Days after Surgery Medications: B-blockers N = 112 High risk vasc surgery Bisoprolol 7-89 days pre-op (mean 37) D(%) MI(%) p CONT 17 17 0.02 BIS 3.4 0 <0.001 Poldermans D et al. NEJM 1999;341:1789

16. Medications: Statins Bauer SM, etal. J Vasc Surg 2010;51:242

17. Medications: Statins N = 497 RCT, mean duration of use 37d MI, Trop T was primary composite outcome Decreased CRP, IL-6 All on b-blocker Schauten O, etal. NEJM 2009;361:10

18. Medications: Statins Schauten O, etal. NEJM 2009;361:10

19. Medications: Statins Metaanalysis of ~800,000 pts for perioperative risk reduction effects Kapoor AS, etal. BMJ doi:10.1136

20. Database study of 2839 patients with PAD Reviewed by ICD-9 codes, pharmacy, and labs How well do we do? Rehring TF, etal. J Vasc Surg 2005;41:816

21. How well do we do? N = 325 vascular surgical patients MarchallC, etal. Vasc Endovasc Surg 2009;43:238

22. How well do we do? NHANES 1999-2004 ABI < .9 Risk adjusted rates of mortality with multiple preventative therapy: HR= .35; 95% CI .2-.86 Prande RL, etal. Circ 2011;124:17.

23. Post Op MI Landesberg G, etal. Circulation 2009;119:2936

24. Post Op MI Landesberg G, etal. Circulation 2009;119:2936

25. Well established guidelines But are they actually followed?

26. Preoperative Evaluation • Accepted and non-controversial indications for full cardiac w/u prior to surgery Fleisher LA, etal. Circulation 2007;116:1971

27. Preop risk tools • RCRI Lee TH, etal. Circulation 1999;100:1043

28. Preoperative Evaluation • Derived from VSGNE (N = 10,081) • Validated • More sensitive in vascular surgical patients than RCRI Bertges DJ, etal. JVS 2010;52:674

29. Preop Risk: Biomarkers N = 2054 elective vascular surgery pts PMCE = MI, pul. edema, death RCRI improved ~ 20% on BB or statin Choi JH, etal. Heart 2010;96:56

30. Preop Risk: Biomarkers N = 91 LEB patients hsCRP, fibrinogen, SAA FU ~ 1 yr Owens CD, etal. JVS 2007;45:2

31. Preop Risk: Biomarkers Metaanalysis of 3,281 pts with perioperative CV complications Karthikeyan G, etal. JACC 2009;54:1599

32. Preop Evaluation Bauer SM, etal. J Vasc Surg 2010;51:242

33. Preop Stress testing Meta-analysis of 68 studies with N = 10,049 LR = 8.35; 5.6-12.5 of po MI if positive Beattie WS, etal. Anesth Analg 2006;102:8

34. Does preoperative stress testing help? N = 99 RCT of preop stress test vs. none after AHA guideline stratification No difference at one year; 1 % CV morbidity/mortality Falcone RA, etal. J Cardio Vasc Anesth 2003;17:694

35. Preop Evaluation: Costs Glance LG, etal. J Card Vasc Anesth 1999;23:265

36. Individual Costs of Preop Work Up EKG = $135 ($75) ECHO = $695 ($325) Stress ECHO = $1708 ($644) Nuclear Stress test = $725 ($282) Catheterization = $3000 ($1013) Consult = $267-453 Professional fees are in ( )

37. Preop Cardiac Revascularization N = 510 RCT of high risk vascular pts Excl: AS, EF < 20%, LM dz McFalls E, etal. NEJM 2004;351:27

38. Preop Cardiac Revascularization N = 101 RCT of high risk pts with ++ stress test 2.8 yr FU No major differences in endpoints Schouten O, etal, JACC 2009;103:897

39. Preop Cardiac Revascularization Biccard BM , etal. Anesthesia 2009;64:1105

40. What probably doesn’t need study • Individual comparison of antiplatelet, statin, b-blocker, and ACEI therapy in vascular disease patient outcomes • Evidence very strong from large CV trials, Registries, Guidelines • Preoperative cardiac revascularization in vascular surgical patients • Done twice; very intensive trials • Antiplatelet therapy types for primary/secondary prevention

41. Current Relevant Trialswww.clinicaltrials.gov • Predictors of po outcome in PV surgical patients • NCT01417910 • Cardiopulmonary exercise testing and preoperative risk stratification • NCT00737828 • Prospective study to assess screening value of NT-proBNP for the identification of pts that benefit from additional cardiac testing prior to vascular surgery • NCT00519961 • POISE-2 (ASA and clonidine) • NCT00144937

42. Current Relevant Trials • Multifactoral Intervention on CV risk factors in subjects with PAD • NCT00144937 • Multifactoral risk reduction for optimal management of PAD • NCT00537225 • Vascular events in noncardiac surgery patients cohort evaluation • NCT00512109

43. Potential Topics to Study • Preoperative cardiac risk stratification comparative study • Risk equation and added biomarkers to increase pretest probability • Preoperative stress testing usefulness • Postoperative MI care – heterogeneous • Large multicenter survey / Study best practices • Intensive vs. usual cardiovascular medical care in high risk arterial disease patients • GWtG/GAP paradigm for following AMI pathway • Active pathway intervention vs. simple recommendation reminders • Steno II paradigm of multimodal intensive therapy for DM

44. GWtG Lewis WR, etal. Arch Int Med 2006;168:1813

45. GAP Eagle KA, etal. JACC 2005;46:1242

46. GAP Eagle KA, etal. JACC 2005;46:1242

47. Steno-2 Model • N = 160 • RCT of intensive multimodality therapy vs. usual care • F/U ~ 8 yrs • Composite endpoint of death, CV morbidity, amputation Gaede P, etal. NEJM 2003;348:383

48. Steno-2 Model Gaede P, etal. NEJM 2003;348:383