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背景无肾病者用他汀类药物降低LDL胆固醇以减少心肌梗死、缺血性脑卒中风险,也是冠脉血管重建的需要,但尚未确定其对中至重度肾病者的作用。此心肾保护研究试验目的 :对这些病人用辛伐他汀加依替米贝联合治疗的有效性及安全性做出评价。方法 本随机双盲试验含9 270例慢性肾病病人(3 023例做透析,6 247例未做透析),无心肌梗死或冠脉血管重建史。将病人随机分组:每日辛伐他汀20 mg加依替米贝10 mg组,或安慰剂对照组。主要预先指定结果为首发严重动脉粥样硬化事件(非致命性心肌梗死或冠心病死亡、非出血性脑卒中或任何动脉血管重建术)。所有分析均采用了治疗意向法。发现将4 650例病人纳入辛伐他汀加依替米贝组,4 620例病人纳入安慰剂组。跟踪中位年为4.9年,辛伐他汀加依替米贝组所产生的平均LDL胆固醇差异为0.85 mmol/L(SE 0.02,治疗依从为2/3);严重动脉粥样硬化事件减少比例17%[辛伐他汀加依替米贝(526,11.3%)对安慰剂组(619,13.4%);RR=0.83,95%CI(0.74,0.94);log-rank P=0.0021]。辛伐他汀加依替米贝组,病人患非致命性心肌梗死或死于冠心病未见明显减少[213,4.6%对230,5.0%;RR=0.92,95%CI(0.76,1.11);P=0.37];而患非出血性脑卒中[131,2.8%对174,3.8%;RR=0.75,95%CI(0.60,0.94);P=0.01]及做动脉血管脉重建术[284,6.1%对352,7.6%;RR=0.79,95%CI(0.68,0.93);P=0.0036]明显要少。亚群组相关LDL胆固醇减少加权检验后,就严重动脉粥样硬化事件而言,未获得此比例作用与被调查的任何亚群组所概述的比率有所不同的良好证据;尤其做透析与未做透析病人,呈现出的作用相似。用此联合疗法,疾病过多风险仅为2/10 000例病人/年(9,0.2%对5,0.1%)。未获得肝炎(21,0.5%对18,0.4%)、胆结石(106,2.3%对106,2.3%)、或癌症(438,9.4%对439,9.5%,P=0.89)过多风险证据,也未发现血管源明显过多死亡(668,14.4%对612,13.2%,P=0.13)。解释 每日用阿伐他汀20 mg加依替米贝10 mg降低LDL胆固醇,安全地减少了大多数慢性肾病病人严重动脉粥样硬化事件的发生率。
BackgroundNine-nephropathy with statins to reduce LDL cholesterol in order to reduce the risk of myocardial infarction, ischemic stroke is also a need for coronary revascularization, but its role in moderate to severe nephropathy has not yet been determined. This Heart-Kidney Protection Study Objectives: To evaluate the efficacy and safety of simvastatin plus ezetimibe in these patients. Methods This randomized double-blind trial included 9,270 patients with chronic kidney disease (3,023 dialysis and 6,247 without dialysis), no history of myocardial infarction or coronary revascularization. Patients were randomized into groups: daily 20 mg simvastatin plus 10 mg ezetimibe, or placebo control. The primary prespecified result is the first severe atherothrombotic event (non-fatal myocardial infarction or coronary heart disease death, non-hemorrhagic stroke or any arterial revascularization). All analyzes used a treatment intention method. A total of 4,650 patients were enrolled in simvastatin plus ezetimibe and 4,620 patients in the placebo group. The mean LDL cholesterol difference between simvastatin and ezetimibe was 0.85 mmol / L (SE 0.02, treatment adherence was 2/3) with a median follow-up of 4.9 years. The rate of reduction of severe atherosclerosis was 17 % [Simvastatin plus ezetimibe (526, 11.3%) vs placebo (619, 13.4%); RR = 0.83, 95% CI (0.74, 0.94); log-rank P = 0.0021]. Simvastatin plus ezetimibe did not show any significant reduction in patients with non-fatal myocardial infarction or death from coronary heart disease [213,4,6% vs 230,5.0%; RR = 0.92,95% CI (0.76,1.11); (P = 0.37); P = 0.37]; and non-hemorrhagic stroke [131,2.8% vs 174,3.8%; RR = 0.75,95% CI 6.1% vs. 352,7.6%; RR = 0.79, 95% CI (0.68, 0.93); P = 0.0036] was significantly less. Subgroup-based LDL-cholesterol-reduced-weighted test for good atherosclerotic events did not give good evidence that this ratio differs from the rates outlined in any of the sub-groups under investigation; in particular, dialysis vs. not Dialysis patients, showing similar role. With this combination the overdose risk is only 2/10 000 patients / year (9,0.2% vs 5,0.1%). No evidence of excessive risk of hepatitis (21,0.5% vs 18,0.4%), gallstone (106,2,3% vs 106,2,3%), or cancer (438,9,4% vs 439,9,5%, P = 0.89) No significant excess of vascular origin was found (668, 14.4% vs. 612, 13.2%, P = 0.13). Explain daily lowering of LDL cholesterol with atvastatin 20 mg plus etimicin 10 mg safely reduces the incidence of severe atherosclerosis in most patients with chronic kidney disease.