阿托伐他汀和瑞舒伐他汀在伴有进行性肾脏疾病的糖尿病患者中的肾脏作用（PLANET I）：一项随机临床试验。
Renal effects of atorvastatin and rosuvastatin in patients with diabetes who have progressive renal disease (PLANET I): a randomised clinical trial.
机构信息
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
AstraZeneca, Wilmington, DE, USA.
出版信息
Lancet Diabetes Endocrinol. 2015 Mar;3(3):181-90. doi: 10.1016/S2213-8587(14)70246-3. Epub 2015 Feb 4.
BACKGROUND
The role of lipid-lowering treatments in renoprotection for patients with diabetes is debated. We studied the renal effects of two statins in patients with diabetes who had proteinuria.
METHODS
PLANET I was a randomised, double-blind, parallel-group trial done in 147 research centres in Argentina, Brazil, Bulgaria, Canada, Denmark, France, Hungary, Italy, Mexico, Romania, and the USA. We enrolled patients with type 1 or type 2 diabetes aged 18 years or older with proteinuria (urine protein:creatinine ratio [UPCR] 500-5000 mg/g) and taking stable angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or both. We randomly assigned participants to atorvastatin 80 mg, rosuvastatin 10 mg, or rosuvastatin 40 mg for 52 weeks. The primary endpoint was change from baseline to week 52 of mean UPCR in each treatment group. The study is registered with ClinicalTrials.gov, number NCT00296374.
FINDINGS
We enrolled 353 patients: 118 were assigned to rosuvastatin 10 mg, 124 to rosuvastatin 40 mg, and 111 to atorvastatin 80 mg; of these, 325 were included in the intention-to-treat population. UPCR baseline:week 52 ratio was 0·87 (95% CI 0·77-0·99; p=0·033) with atorvastatin 80 mg, 1·02 (0·88-1·18; p=0·83) with rosuvastatin 10 mg, and 0·96 (0·83-1·11; p=0·53) with rosuvastatin 40 mg. In a post-hoc analysis to compare statins, we combined data from PLANET I with those from PLANET II (a similar randomised parallel study of 237 patients with proteinuria but without diabetes; registered with ClinicalTrials.gov, NCT00296400). In this analysis, atorvastatin 80 mg lowered UPCR significantly more than did rosuvastatin 10 mg (-15·6%, 95% CI -28·3 to -0·5; p=0·043) and rosuvastatin 40 mg (-18·2%, -30·2 to -4·2; p=0·013). Adverse events occurred in 69 (60%) of 116 patients in the rosuvastatin 10 mg group versus 79 (64%) of 123 patients in the rosuvastatin 40 mg group versus 63 (57%) of 110 patients in the atorvastatin 80 mg group; renal events occurred in nine (7·8%) versus 12 (9·8%) versus five (4·5%).
INTERPRETATION
Despite high-dose rosuvastatin lowering plasma lipid concentrations to a greater extent than did high-dose atorvastatin, atorvastatin seems to have more renoprotective effects for the studied chronic kidney disease population.
FUNDING
AstraZeneca.
背景
降脂治疗在糖尿病患者的肾脏保护中的作用存在争议。我们研究了两种他汀类药物在伴有蛋白尿的糖尿病患者中的肾脏作用。
方法
PLANET I 是一项在阿根廷、巴西、保加利亚、加拿大、丹麦、法国、匈牙利、意大利、墨西哥、罗马尼亚和美国的 147 个研究中心进行的随机、双盲、平行组试验。我们招募了年龄在 18 岁及以上、有蛋白尿（尿蛋白：肌酐比值 [UPCR] 500-5000mg/g）且正在服用稳定的血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂或两者的 1 型或 2 型糖尿病患者。我们将参与者随机分配至阿托伐他汀 80mg、瑞舒伐他汀 10mg 或瑞舒伐他汀 40mg 治疗 52 周。主要终点是每组治疗的平均 UPCR 从基线到第 52 周的变化。该研究在 ClinicalTrials.gov 上注册，编号为 NCT00296374。
结果
我们共招募了 353 名患者：118 名患者被分配至瑞舒伐他汀 10mg 组，124 名患者被分配至瑞舒伐他汀 40mg 组，111 名患者被分配至阿托伐他汀 80mg 组；其中 325 名患者被纳入意向治疗人群。UPCR 基线：第 52 周比值为 0.87（95%CI 0.77-0.99；p=0.033），阿托伐他汀 80mg 组为 1.02（0.88-1.18；p=0.83），瑞舒伐他汀 10mg 组为 0.96（0.83-1.11；p=0.53），瑞舒伐他汀 40mg 组为 0.96（0.83-1.11；p=0.53）。在一项事后分析中，我们将 PLANET I 的研究数据与 PLANET II（一项针对 237 名伴有蛋白尿但无糖尿病的患者的类似随机平行研究；在 ClinicalTrials.gov 上注册，编号为 NCT00296400）的数据进行了合并。在这项分析中，阿托伐他汀 80mg 比瑞舒伐他汀 10mg 显著降低 UPCR（-15.6%，95%CI-28.3 至-0.5；p=0.043）和瑞舒伐他汀 40mg（-18.2%，-30.2 至-4.2；p=0.013）。在瑞舒伐他汀 10mg 组中，116 名患者中有 69 名（60%）发生不良事件，瑞舒伐他汀 40mg 组中有 123 名患者中有 79 名（64%）发生不良事件，阿托伐他汀 80mg 组中有 110 名患者中有 63 名（57%）发生不良事件；在瑞舒伐他汀 10mg 组中有 9 名（7.8%）发生肾脏事件，瑞舒伐他汀 40mg 组中有 12 名（9.8%）发生肾脏事件，阿托伐他汀 80mg 组中有 5 名（4.5%）发生肾脏事件。
解释
尽管高剂量瑞舒伐他汀降低血浆脂质浓度的程度大于高剂量阿托伐他汀，但阿托伐他汀似乎对所研究的慢性肾病患者具有更强的肾脏保护作用。
资金来源
阿斯利康。
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