Study of Heart and Renal Protection (SHARP): Randomized trial to assess the effects of lowering low-density lipoprotein cholesterolamong 9,438patients with chronic kidney disease
摘要：患者采用他汀类药物治疗后，低密度脂蛋白胆固醇明显下降，动脉粥样硬化事件的发生率也有所下降。但是对于患有长期肾病的患者，效果不明确有待进一步的研究。结论：通过对患有慢性肾病的9,438患者进行随机调查研究，证实依折麦布/辛伐他汀联合用药具有良好的治疗疗效和安全性耐受性。
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 μmol/L] in men or ≥1.5 mg/dL [ ≥ 130 μmol/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.
