BACKGROUND: Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD). METHODS: Patients with advanced CKD (blood creatinine >/= 1.7 mg/dL [>/= 150 mumol/L] in men or >/= 1.5 mg/dL [ >/= 130 mumol/L] in women) with no known history of myocardial infarction or coronary revascularization were randomized in a ratio of 4:4:1 to ezetimibe 10 mg plus simvastatin 20 mg daily versus matching placebo versus simvastatin 20 mg daily (with the latter arm rerandomized at 1 year to ezetimibe 10 mg plus simvastatin 20 mg daily vs placebo). The key outcome will be major atherosclerotic events, defined as the combination of myocardial infarction, coronary death, ischemic stroke, or any revascularization procedure. RESULTS: A total of 9,438 CKD patients were randomized, of whom 3,056 were on dialysis. Mean age was 61 years, two thirds were male, one fifth had diabetes mellitus, and one sixth had vascular disease. Compared with either placebo or simvastatin alone, allocation to ezetimibe plus simvastatin was not associated with any excess of myopathy, hepatic toxicity, or biliary complications during the first year of follow-up. Compared with placebo, allocation to ezetimibe 10 mg plus simvastatin 20 mg daily yielded average LDL cholesterol differences of 43 mg/dL (1.10 mmol/L) at 1 year and 33 mg/dL (0.85 mmol/L) at 2.5 years. Follow-up is scheduled to continue until August 2010, when all patients will have been followed for at least 4 years. CONCLUSIONS: SHARP should provide evidence about the efficacy and safety of lowering LDL cholesterol with the combination of ezetimibe and simvastatin among a wide range of patients with CKD.
AN - 21095263 BT - American Heart Journal ET - 2010/11/26 LA - eng M1 - 5 N1 - British Heart Foundation/United KingdomMedical Research Council/United KingdomComparative StudyMulticenter StudyRandomized Controlled TrialResearch Support, Non-U.S. Gov'tUnited StatesAmerican heart journalAm Heart J. 2010 Nov;160(5):785-794.e10. Epub 2010 Sep 18. N2 -BACKGROUND: Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD). METHODS: Patients with advanced CKD (blood creatinine >/= 1.7 mg/dL [>/= 150 mumol/L] in men or >/= 1.5 mg/dL [ >/= 130 mumol/L] in women) with no known history of myocardial infarction or coronary revascularization were randomized in a ratio of 4:4:1 to ezetimibe 10 mg plus simvastatin 20 mg daily versus matching placebo versus simvastatin 20 mg daily (with the latter arm rerandomized at 1 year to ezetimibe 10 mg plus simvastatin 20 mg daily vs placebo). The key outcome will be major atherosclerotic events, defined as the combination of myocardial infarction, coronary death, ischemic stroke, or any revascularization procedure. RESULTS: A total of 9,438 CKD patients were randomized, of whom 3,056 were on dialysis. Mean age was 61 years, two thirds were male, one fifth had diabetes mellitus, and one sixth had vascular disease. Compared with either placebo or simvastatin alone, allocation to ezetimibe plus simvastatin was not associated with any excess of myopathy, hepatic toxicity, or biliary complications during the first year of follow-up. Compared with placebo, allocation to ezetimibe 10 mg plus simvastatin 20 mg daily yielded average LDL cholesterol differences of 43 mg/dL (1.10 mmol/L) at 1 year and 33 mg/dL (0.85 mmol/L) at 2.5 years. Follow-up is scheduled to continue until August 2010, when all patients will have been followed for at least 4 years. CONCLUSIONS: SHARP should provide evidence about the efficacy and safety of lowering LDL cholesterol with the combination of ezetimibe and simvastatin among a wide range of patients with CKD.
PY - 2010 SN - 1097-6744 (Electronic)0002-8703 (Linking) SP - 785 EP - 794 e10 T2 - American Heart Journal TI - Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease VL - 160 ER -