HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis

Palmer Suetonia C.; Navaneethan Sankar D.; Craig Jonathan C.; Johnson David W.; Perkovic Vlado; Hegbrant Jorgen; Strippoli Giovanni F. M.

摘要

BACKGROUND: Cardiovascular disease (CVD) is the most frequent cause of death in people with early stages of chronic kidney disease (CKD), for whom the absolute risk of cardiovascular events is similar to people who have existing coronary artery disease. This is an update of a review published in 2009, and includes evidence from 27 new studies (25,068 participants) in addition to the 26 studies (20,324 participants) assessed previously; and excludes three previously included studies (107 participants). This updated review includes 50 studies (45,285 participants); of these 38 (37,274 participants) were meta-analysed. OBJECTIVES: To evaluate the benefits (such as reductions in all-cause and cardiovascular mortality, major cardiovascular events, MI and stroke; and slow progression of CKD to end-stage kidney disease (ESKD)) and harms (muscle and liver dysfunction, withdrawal, and cancer) of statins compared with placebo, no treatment, standard care or another statin in adults with CKD who were not on dialysis. METHODS: Search methods: We searched the Cochrane Renal Group's Specialised Register to 5 June 2012 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of statins with placebo, no treatment, standard care, or other statins, on mortality, cardiovascular events, kidney function, toxicity, and lipid levels in adults with CKD not on dialysis were the focus of our literature searches. Data collection and analysis: Two or more authors independently extracted data and assessed study risk of bias. Treatment effects were expressed as mean difference (MD) for continuous outcomes (lipids, creatinine clearance and proteinuria) and risk ratio (RR) for dichotomous outcomes (major cardiovascular events, all-cause mortality, cardiovascular mortality, fatal or non-fatal myocardial infarction (MI), fatal or non-fatal stroke, ESKD, elevated liver enzymes, rhabdomyolysis, cancer and withdrawal rates) with 95% confidence intervals (CI). MAIN RESULTS: We included 50 studies (45,285 participants): 47 studies (39,820 participants) compared statins with placebo or no treatment and three studies (5547 participants) compared two different statin regimens in adults with CKD who were not yet on dialysis. We were able to meta-analyse 38 studies (37,274 participants). The risk of bias in the included studies was high. Seven studies comparing statins with placebo or no treatment had lower risk of bias overall; and were conducted according to published protocols, outcomes were adjudicated by a committee, specified outcomes were reported, and analyses were conducted using intention-to-treat methods. In placebo or no treatment controlled studies, adverse events were reported in 32 studies (68%) and systematically evaluated in 16 studies (34%). Compared with placebo, statin therapy consistently prevented major cardiovascular events (13 studies, 36,033 participants; RR 0.72, 95% CI 0.66 to 0.79), all-cause mortality (10 studies, 28,276 participants; RR 0.79, 95% CI 0.69 to 0.91), cardiovascular death (7 studies, 19,059 participants; RR 0.77, 95% CI 0.69 to 0.87) and MI (8 studies, 9018 participants; RR 0.55, 95% CI 0.42 to 0.72). Statins had uncertain effects on stroke (5 studies, 8658 participants; RR 0.62, 95% CI 0.35 to 1.12). Potential harms from statin therapy were limited by lack of systematic reporting and were uncertain in analyses that had few events: elevated creatine kinase (7 studies, 4514 participants; RR 0.84, 95% CI 0.20 to 3.48), liver function abnormalities (7 studies, RR 0.76, 95% CI 0.39 to 1.50), withdrawal due to adverse events (13 studies, 4219 participants; RR 1.16, 95% CI 0.84 to 1.60), and cancer (2 studies, 5581 participants; RR 1.03, 95% CI 0.82 to 130). Statins had uncertain effects on progression of CKD. Data for relative effects of intensive cholesterol lowering in people with early stages of kidney disease were sparse. Statins clearly reduced risks of death, major cardiovascular events, and MI in people with CKD who did not have CVD at baseline (primary prevention). AUTHORS' CONCLUSIONS: Statins consistently lower death and major cardiovascular events by 20% in people with CKD not requiring dialysis. Statin-related effects on stroke and kidney function were found to be uncertain and adverse effects of treatment are incompletely understood. Statins have an important role in primary prevention of cardiovascular events and mortality in people who have CKD.

机译：背景：心血管疾病（CVD）是慢性肾脏病（CKD）早期阶段最常见的死亡原因，对于他们来说，发生心血管事件的绝对风险与患有冠心病的人相似。这是对2009年发表的评论的更新，除先前评估的26项研究（20,324名参与者）外，还包括27项新研究（25,068名参与者）的证据;并排除了之前纳入的三项研究（107名参与者）。这份更新后的评论包括50项研究（45,285名参与者）;在这38名（37,274名参与者）中进行了荟萃分析。目的：评估益处（例如降低全因和心血管疾病死亡率，重大心血管事件，心梗和中风;以及将CKD缓慢进展为终末期肾脏疾病（ESKD））和危害（肌肉和肝功能障碍，停药）他汀类药物与安慰剂相比，未经治疗，标准治疗或其他他汀类药物成人未经透析的CKD的比较。方法：搜索方法：我们通过与试验的搜索协调员联系，使用与此评价相关的搜索词，搜索了截至2012年6月5日的Cochrane肾脏小组的专业登记册。选择标准：比较了他汀类药物与安慰剂，未治疗，标准护理或其他他汀类药物对成年CKD成人死亡率，心血管事件，肾功能，毒性和脂质水平的影响的随机对照试验（RCT）和准RCT不是透析是我们文献检索的重点。数据收集和分析：两个或更多作者独立提取数据并评估研究偏倚的风险。治疗效果表示为连续结果（脂质，肌酐清除率和蛋白尿）的平均差（MD）和二分结果（重大心血管事件，全因死亡率，心血管死亡率，致命或非致命性心肌梗塞的风险比）（MI），致命或非致命性中风，ESKD，肝酶升高，横纹肌溶解，癌症和停药率），置信区间（CI）为95％。主要结果：我们纳入了50项研究（45,285名参与者）：47项研究（39,820名参与者）比较了他汀类药物与安慰剂或未治疗的比较，三项研究（5547名参与者）比较了两种尚未接受透析的CKD成人他汀类药物方案。我们能够进行荟萃分析38项研究（37,274名参与者）。纳入研究的偏倚风险很高。七项比较他汀类药物与安慰剂或不治疗的研究总体上有较低的偏倚风险;并根据已发布的方案进行，结果由委员会裁决，报告特定结果，并使用意向性治疗方法进行分析。在安慰剂或无治疗对照研究中，不良事件在32项研究中报告（68％），在16项研究中系统评价（34％）。与安慰剂相比，他汀类药物疗法始终预防重大心血管事件（13个研究，36,033名参与者; RR 0.72，95％CI 0.66至0.79），全因死亡率（10个研究，28,276名参与者; RR 0.79，95％CI 0.69至0.91），心血管死亡（7个研究，19059名参与者; RR 0.77，95％CI 0.69至0.87）和MI（8个研究，9018名参与者; RR 0.55，95％CI 0.42至0.72）。他汀类药物对中风的影响不确定（5个研究，8658名参与者; RR 0.62，95％CI 0.35至1.12）。他汀类药物治疗的潜在危害由于缺乏系统的报道而受到限制，并且在很少发生事件的分析中不确定：肌酸激酶升高（7个研究，4514名参与者; RR 0.84，95％CI 0.20至3.48），肝功能异常（7个研究， RR 0.76，95％CI 0.39至1.50），因不良事件而退出治疗（13个研究，4219名参与者; RR 1.16，95％CI 0.84至1.60）和癌症（2个研究，5581名参与者; RR 1.03，95％CI 0.82至130）。他汀类药物对CKD进展的影响不确定。在早期肾脏疾病患者中，密集的降低胆固醇的相对作用的数据很少。他汀类药物明显降低了基线时没有CVD的CKD患者的死亡，重大心血管事件和MI的风险（一级预防）。作者的结论：在不需要透析的CKD患者中，他汀类药物可将死亡和重大心血管事件持续降低20％。发现他汀类药物对中风和肾功能的影响尚不确定，并且对治疗的不良影响尚不完全清楚。他汀类药物在患有CKD的人的心血管事件和死亡率的一级预防中具有重要作用。

HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis

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