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

• 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

• 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.

• • Baseline characteristics were well balanced… Median duration of follow up….4.9 yrs • Simvastatin plus ezetimibe grp….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 ezetimibe vs 619 [13·4%] placebo; p=0·0021). • • Significant redn in nonhgic stroke (131 vs 174…P 0.01), arterial revascularisation procedures(284 vs 352 ….P=0.0036) Nonfatal MI…Nonsignif reduction

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

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.

THANK YOU

• MDRD equation