6/29/23, 11:41 PM SHARP Pathway Feedback Search Clinical Topics Home Studies SHARP SHARP Disease Disease Chronic kidney disease Dyslipidemia Trial question What is the role of simvastatin plus ezetimibe in patients with advanced CKD? Study design Multi-center Double blinded RCT Population Characteristics of study participants 37.0% female N = 9270 63.0% male 9270 patients (3470 female, 5800 male) Inclusion criteria: patients with advanced CKD Key exclusion criteria: history of MI or coronary revascularization procedure, history of chronic liver disease, active inflammatory muscle disease, previous adverse reaction to a statin or to ezetimibe, concurrent treatment with a contraindicated drug, or child-bearing potential Interventions N=4650 simvastatin plus ezetimibe (20 mg simvastatin and 10 mg ezetimibe daily) N=4620 placebo (matching placebo daily) Primary outcome Major atherosclerotic events https://web.pathway.md/studies/recCX2JiFqmVbhuyK 1/2 6/29/23, 11:41 PM SHARP Pathway 13.4 % 13.4 11.3 10.1 % 6.7 % Significant decrease 3.4 % NNT = 48 0.0 % Simvastatin plus ezetimibe Placebo Significant decrease in major atherosclerotic events (11.3% vs. 13.4%; RR 0.83, 95% CI 0.74 to 0.94) Secondary outcomes No significant difference in nonfatal myocardial infarction or death from coronary artery disease (4.6% vs. 5%; RR 0.92, 95% CI 0.76 to 1.11) Significant decrease in non-hemorrhagic stroke (2.8% vs. 3.8%; RR 0.75, 95% CI 0.6 to 0.94) Significant decrease in arterial revascularisation procedures (6.1% vs. 7.6%; RR 0.79, 95% CI 0.68 to 0.93) Safety outcomes No significant differences in excess risk of myopathy (0.2% vs. 0.1%), hepatitis (0.5% vs. 0.4%) gallstones (2.3% vs. 2.3%), or cancer (9.4% vs. 9.5%, p=0.89), or excess of death from any non- vascular cause (14.4% vs. 13.2%, p=0.13). Conclusion In patients with advanced CKD, simvastatin plus ezetimibe was superior to placebo with respect to major atherosclerotic events. Reference Baigent C, Landray MJ, Reith C et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011 Jun 25;377(9784):2181-92. Open reference URL https://web.pathway.md/studies/recCX2JiFqmVbhuyK 2/2