- The document discusses the evidence for lipid lowering therapy in patients with chronic kidney disease (CKD). It summarizes data from major trials showing proportional reductions in major vascular events with reductions in LDL cholesterol. - For patients at high risk of atherosclerotic events like those with diabetes or known heart disease, statin therapy may provide similar benefits regardless of kidney function, though the evidence is less clear for patients on dialysis or with mild CKD. - Ongoing trials like SHARP and AURORA aim to provide more evidence on the risks and benefits of statin therapy in patients with CKD or on dialysis.

1. Lipid lowering therapy in CKD What is the evidence? Conall O’ Seaghdha Renal Meeting Royal North Shore Hospital 29/08/07

3. Patients with known CHD, or other high-risk condition (e.g. diabetes mellitus)

6. Proportional effects on MAJOR VASCULAR EVENTS* by mean difference in LDL cholesterol * MI, coronary death, stroke or coronary revascularisation

8. Cholesterol Treatment Trialists' (CTT) Collaborators. Lancet 2005 Proportional effects on cause-specific mortality per 1mmol/L LDL-cholesterol reduction 1.01 (0.91-1.12) 2.4 2.4 Cancer 0.95 (0.90-1.01) 4.0 3.8 Any nonvascular 0.83 (0.79-0.87) 5.7 4.7 Any vascular 0.95 (0.78-1.16) 0.7 0.6 Other vascular 0.91 (0.74-1.11) 0.6 0.6 Stroke 0.93 (0.83-1.03) 1.3 1.2 Any non-coronary-heart-disease 0.81 (0.76-0.85) 4.4 3.4 Coronary heart disease 0.88 (0.84-0.91) 9.7 8.5 All-cause Relative risk (95% CI) Control-arm events, % (n=45 002) Treatment-arm events, % (n=45 054 ) Cause of death

10. Cholesterol Treatment Trialists' (CTT) Collaborators. Lancet 2005 Proportional effects on major coronary events per 1-mmol/L LDL-cholesterol reduction subdivided by baseline LDL cholesterol 22% (15%, 28%) 23% (20%, 26%) 1120 (12.9) 4420 (9.8) 801 (9.3) 3337 (7.4) >4.5 mmol/l Overall 23% (17%, 29%) 1814 (9.6) 1374 (7.3) 3.5-4.5 mmol/l 24% (16%, 32%) 1443 (8.7) 1130 (6.8) <3.5 mmol/l Rate Reduction (95% CI) Control-arm events, % Treatment-arm events, % Groups

11. K/DOQI Stages of Chronic Kidney Disease RRT/Conservative 0-14 5 More Complications Referral/Preparation 15-29 4 Complications Progression/Referral 30-59 3 Hypertension Structural problem 60-89 2* Hypertension Structural problem >90 1* Comment GFR (ml/min/1.73m2) Stage

13. Benefits of pravastatin on major coronary event or revascularisation in the CARE, LIPID and WOSCOPS trials, by eGFR Pravastatin Pooling Project Tonelli et al. Circulation 2004;110;1557-1563 0.71-1.01 0.85 >90 0.74-0.88 0.81 60-89.9 0.71-0.88 0.79 <60 95% confidence interval Relative risk eGFR (ml/min/1.73m2)

14. Among patients with known CHD , proportional benefits of statins appear similar irrespective of eGFR

16. K/DOQI Stages of Chronic Kidney Disease RRT/Conservative 0-14 5 More Complications Referral/Preparation 15-29 4 Complications Progression/Referral 30-59 3 Hypertension Structural problem 60-89 2* Hypertension Structural problem >90 1* Comment GFR (ml/min/1.73m2) Stage

17. Cardiovascular Mortality in Dialysis Patients Sarnak, M. J. et al. Circulation 2003;108:2154-2169

18. Reverse Epidemiology: Cholesterol Lowrie EG Am J Kidney Dis 15:458-482, 1990

20. Causes of death in dialysis patients USRDS 1996 Annual Data Report

21. Causes of death in dialysis patients USRDS 1996 Annual Data Report

22. Causes of death in dialysis patients USRDS 1996 Annual Data Report

24. ECHO findings predict survival in haemodialysis patients Parfrey P et al NDT 1996

25. Coronary Calcification in Dialysis Patients

26. Atorvastatin in Patients with Type 2 Diabetes Mellitus Undergoing Hemodialysis Christoph Wanner, M.D., Vera Krane, M.D., Winfried Marz, M.D., Manfred Olschewski, M.Sc., Johannes F.E. Mann, M.D., Gunther Ruf, M.D., Eberhard Ritz, M.D. and the German Diabetes and Dialysis Study Investigators N Engl J Med Volume 353;3:238-248 July 21, 2005

30. Study Protocol Wanner, C. et al. N Engl J Med 2005;353:238-248

31. Baseline Characteristics of Patients Wanner, C. et al. N Engl J Med 2005;353:238-248

32. Baseline Characteristics of Patients Wanner, C. et al. N Engl J Med 2005;353:238-248

33. Median Level of Low-Density Lipoprotein (LDL) Cholesterol Wanner, C. et al. N Engl J Med 2005;353:238-248

34. Estimated Cumulative Incidence of the Composite Primary End Point Wanner, C. et al. N Engl J Med 2005;353:238-248

35. Rates of Primary and Secondary End Points Wanner, C. et al. N Engl J Med 2005;353:238-248

36. Adverse Events Wanner, C. et al. N Engl J Med 2005;353:238-248

38. Different causes of death in 4D and CTT 44% 50% Non-vascular 7% 6% Stroke 7% 35% Other cardiac 42% 9% CHD CTT 4D Cause of death

39. Expected versus observed effects on endpoints in the 4D trial 0.93 (0.79-1.08) 0.93 All-cause mortality 1.33 (0.90-1.97) 0.75 Stroke 0.82 (0.68-0.99) 0.84 Cardiac events 0.92 (0.77-1.10) 0.83 Primary endpoint Observed Expected Endpoint

41. K/DOQI Stages of Chronic Kidney Disease RRT/Conservative 0-14 5 More Complications Referral/Preparation 15-29 4 Complications Progression/Referral 30-59 3 Hypertension Structural problem 60-89 2* Hypertension Structural problem >90 1* Comment GFR (ml/min/1.73m2) Stage

45. Transplant patients