SVS Clinical Research Priorities Hemodialysis Access

1. SVS Clinical Research Priorities Hemodialysis Access Thomas S. Huber, MD, PhD Professor and ChiefDivision of Vascular Surgery University of Florida College of Medicine

2. Patient Counts by Treatment for ESRD

3. Prevalent Counts by Modality 65% 30% 5%

4. 5-year Mortality by Incident Access

5. Admission and LOS by Modality

6. Catheter Events and Complications

7. Fistula Events and Complications

8. Medicare Patients and Cost - 2006

9. Medicare Expenditure – ESRD pt/yr $77K $72K $53K

11. Kidney Disease Outcomes Quality Initiative (KDOQI) – Access • NKF guidelines and practice recommendations. • Access guidelines – 1997, 2000, 2006. • Evidence-based approach. • Literature review. • Multidisciplinary work group. • THE GUIDELINES for access care.

12. KDOQI – Overall Goals • Increase use of AV fistula (autogenous). • Detect access dysfunction before thrombosis. • 2006 - AVF > 65%, catheters < 10%.

13. KDOQI – Guidelines • Patient preparation for permanent access. • Selection and placement of access. • Cannulation and accession. • Access dysfunction.

14. KDOQI – Guidelines • Treatment of AV fistula complications. • Treatment of AV graft complications. • Treatment of catheter complications. • Clinical outcome goals.

15. SVS Clinical Practice Guidelines • Multidisciplinary group to optimize AV fistula. • Systematic review of evidence (external). • Timing of access referral. • Type of access. • Effectiveness of surveillance.

16. SVS Clinical Practice Guidelines • Timing of referral to access surgeon. • Strategies to optimize AV fistula. • First choice of access – forearm AV fistula. • Choice of access after forearm AV fistula.

17. SVS Clinical Practice Guidelines • Role of monitoring and surveillance. • Conversion of AV graft to AV fistula. • Management of non-functional access.

18. Fistula First Breakthrough Initiative (FFBI) • CMS multi-year initiative to increase AV fistula rates (2003 – 2006). • Multidisciplinary approach - ESRD networks. • KDOQI AV fistula goals • Initial – 50% incidence, 40% prevalence. • Updated – 66% prevalence by 2009.

19. Mission of FFBI • Maximize AVF in all suitable patients. • Minimize dialysis catheter use. • Avoid all types of access complications. *Implemented through “Change Concepts”

20. FFBI AVF Total CVC Total CVC

22. Limitations - Guidelines/Initiatives • Quality of the underlying evidence. • Outcomes may not be achievable. • Potential unintended consequences of emphasis on AV fistula. • Increased catheter use. • Increased AV fistula failure. *New emphasis on “functional” access.

23. Randomized Trials and Meta-analyses • Preoperative strategies. • Ultrasound vein survey (benefit). • MR vs contrast venogram (comparable). • Intraoperative strategies. • Anticoagulation (no benefit). • Anesthesia –stellate block (benefit). • Staples vs suture (likely comparable).

24. Randomized Trials and Meta-analyses • Selection of access type. • AVF vs prosthetic (AVF better). • Role of radiocephalic (high failure). • Radiocephalic vs forearm prosthetic. • Brachiobasilic vs prosthetic (BB better). • Brachiobasilic vs brachiocephalic (comparable). • Elderly patients (proximal access). • One vs two stage brachiobasilic (two stage better).

25. Randomized Trials and Meta-analyses • Choice of prosthetic/biologic graft. • Biologic vs PTFE (likely comparable). • PTFE vs PTFE (comparable). • Cuffed vs non-cuffed PTFE (cuff better). • PTFE vs TTFE (comparable). • Taper vs non taper PTFE (likely comparable).

26. Randomized Trials and Meta-analyses • Strategies to increase patency/decrease neointimal hyperplasia. • Medical. • Antiplatelet agents (no benefit). • Fish oil (no benefit). • Multiple others (unpublished or in progress). • Topical. • Paclitaxel (unpublished or in progress). • Radiation (no benefit).

27. Randomized Trials and Meta-analyses • Surveillance/remediation (potential benefit). • Ultrasound. • Flow. • Venous pressures. • Pre-emptive angioplasty.

28. Randomized Trials and Meta-analyses • Management of complications. • Access thrombosis. • Open vs endovascular (open likely better). • Mechanical vs chemical (comparable). • Venous outflow stenosis. • Cutting balloons (no benefit). • Stents vs angioplasty (no benefit). • Covered stent vs angioplasty (covered better). • Covered stent vs non-covered (covered better). • Heparin-coated balloons (no benefit).

29. Limitations – RCT/Meta-analysis • Device/medication development trials. • Predominantly industry funding source. • Experimental design. • Small sample size. • Single center.

30. Dialysis Access Consortium (DAC) • NIDDK/NIH Consortium started in 2000. • Develop access clinical trials. • Role of pharmacologic agents. • Background of national AVF initiatives.

31. Dember JAMA 2008;299:2164

32. AVF/Clopidogrel - Hypothesis • Clopidogrel will reduce the occurrence of early AVF thrombosis and increase the proportion of new AVF that can be used for hemodialysis.

33. *Clopidogrel did not facilitate AVF maturation – 62% failure, no difference in adverse events including bleeding.

34. Dixon NEJM 2009;360:2191.

35. AVG/DP/ASA - Hypothesis • DP/ASA can prevent stenosis and prolong survival of AVGs.

36. *no difference in cumulative patency, death, adverse outcome. Median cumulative patency rate 22.5 mos

37. Identification of Factors Associated with Failure of Arteriovenous Fistulas to Mature in Hemodialysis Patients (U01) Prospective multi-center observational cohort study investigating clinical factors predictive of and/or associated with failure of newly placed AVF to mature

38. Hemodialysis Fistula Maturation (HFM) Study Objectives Domains - anatomy, biology , patient-specific attributes, process of care 38 • To identify predictors of AVF maturation. • To evaluate mechanisms of AVF maturation.

39. HFM Study Design 39 • Prospective cohort study of 600 patients undergoing construction of AVF. • Participating centers • Clinical sites (Boston, Cincinnati, Utah, Florida, Washington, Texas-SW. • Cores (Histology, Ultrasound, Physiology). • Data coordinating (Cleveland Clinic).

40. HFM Outcome Measures • Primary - unassisted clinical maturation • Use of the AVF with two needles for 75% of dialysis sessions within a 4-week period • Secondary – other maturation endpoints

41. HFM Unique Features • Vascular physiological testing. • Attributes of clinical care. • Serial ultrasound measurements. • Stored blood and tissue samples.

43. Challenges/Specific Questions • AV fistula vs AV graft (specific scenarios). • Impact of comorbidities on access choice. • Access choice after failed forearm access. • Two stage vs one stage brachiobasilic. • Impact of graft modification on patency.

44. Challenges/Specific Questions • Role of surveillance and remediation. • Management of access complications. • Central vein stenoses. • Access-related hand ischemia • Venous outflow stenosis. • Thrombosed accesses.

45. Challenges/Specific Questions • Algorithm for “complex” access. • Impact of access on quality of life. • Development of catheter-free algorithms. • Optimal process of care

46. Low quality evidence from inconsistent studies with limited protection against bias shows that autogenous access for chronic hemodialysis is superior to prosthetic access. J Vasc Surg 2008;48:34S.

47. Very low quality evidence yielding imprecise results suggests a potentially beneficial effect of AV access surveillance followed by interventions to restore patency. J Vasc Surg 2008;48:48S.

48. Proposed Research Emphasis • Develop a patient-centric, cost-effective algorithm for hemodialysis access. • Initial/subsequent access. • Strategies to facilitate AV fistula maturation. • Surveillance and remediation. • Management of complications.

49. Feasibility of Hemodialysis Access Trial • Significant problem with large patient population. • Low quality evidence with multiple questions. • National funding agency receptive. • Recognize magnitude of problem. • Commitment to clinical problem. • Ongoing discussion about next trial. • Potential for surgeon leadership. *Key to identify “the” most compelling question.

50. Summary • Maintaining hemodialysis access is a tremendous public health problem in terms of the number of affected lives, associated morbidity/mortality and overall societal cost. • The national guidelines and initiatives have defined access care although the supporting evidence is limited.