SHARP trial

1. SHARP trial Study of Heart and Renal Protection : a randomised placebo-controlled trial The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with CKD Lancet June 9, 2011

2. To assess the safety and efficacy of reducing LDL cholesterol in CKD Inclusion criteria 1)History of CKD……. pre-dialysis …..creatinine>1.7 mg/dl in men ; >1.5 mg/dl in women dialysis 2)Men or women aged >40 years • 9270 patients with CKD (3023 on dialysis and 6247 not) with no known h/o MI or coronary revascularisation

3. Randomised to simvastatin 20 mg plus ezetimibe 10 mg daily(4650pts) versus matching placebo(4620 pts). • The key prespecified outcome was first major atherosclerotic event (non-fatal MI or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). • All analyses were by intention to treat.

4. Baseline characteristics were well balanced… • Median duration of follow up….4.9 yrs • Simvastatin plus ezetimibegrp….yielded an average LDL cholesterol difference of 0·85 mmol/L and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibevs619 [13·4%] placebo; p=0·0021). • Significant redn in nonhgic stroke (131 vs 174…P 0.01), arterial revascularisationprocedures(284 vs 352 ….P=0.0036) • Nonfatal MI…Nonsignifreduction

6. Among the ‘not on dialysis’ grp(6247 pts)…. simvastatin plus ezetimibe …. No significant reductions in : • ESRD defined as commencement of maintenance dialysis or transplantation (1057 [33·9%] vs 1084 [34·6%]; p=0·41); • ESRD or death (1477 [47·4%] vs 1513 [48·3%]; p=0·34); • ESRD or doubling of baseline creatinine (1190 [38·2%] vs 1257 [40·2%]; p=0·09).

7. Conclusion…….lowering LDL with the combination of simvastatin plus ezetimibe safely reduces the risk of major atherosclerotic events in a wide range of patients with CKD.

8. THANK YOU

11. MDRD equation