BACKGROUND Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent microalbuminuria in normoalbuminuric type 2 diabetic patients. We assessed whether combined therapy with the 2 medications may prevent microalbuminuria better than ACE inhibitor or ARB monotherapy. METHODS AND FINDINGS VARIETY was a prospective, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether, at similar blood pressure (BP) control, combined therapy with benazepril (10 mg/day) and valsartan (160 mg/day) would prevent microalbuminuria more effectively than benazepril (20 mg/day) or valsartan (320 mg/day) monotherapy in 612 type 2 diabetic patients with high-normal albuminuria included between July 2007 and April 2013 by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS and 8 diabetology or nephrology units in Italy. Time to progression to microalbuminuria was the primary outcome. Analyses were intention to treat. Baseline characteristics were similar among groups. During a median [interquartile range, IQR] follow-up of 66 [42 to 83] months, 53 patients (27.0%) on combination therapy, 57 (28.1%) on benazepril, and 64 (31.8%) on valsartan reached microalbuminuria. Using an accelerated failure time model, the estimated acceleration factors were 1.410 (95% CI: 0.806 to 2.467, P = 0.229) for benazepril compared to combination therapy, 0.799 (95% CI: 0.422 to 1.514, P = 0.492) for benazepril compared to valsartan, and 1.665 (95% CI: 1.007 to 2.746, P = 0.047) for valsartan compared to combination therapy. Between-group differences in estimated acceleration factors were nonsignificant after adjustment for predefined confounders. BP control was similar across groups. All treatments were safe and tolerated well, with a slight excess of hyperkalemia and hypotension in the combination therapy group. The main study limitation was the lower than expected albuminuria at inclusion. CONCLUSIONS Risk/benefit profile of study treatments was similar. Dual renin-angiotensin system (RAS) blockade is not recommended as compared to benazepril or valsartan monotherapy for prevention of microalbuminuria in normoalbuminuric type 2 diabetic patients. TRIAL REGISTRATION EudraCT 2006-005954-62; ClinicalTrials.gov NCT00503152.

中文翻译：

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使用贝那普利、缬沙坦和贝那普利 - 缬沙坦联合治疗预防高蛋白尿的糖尿病患者出现微量白蛋白尿：一项前瞻性、随机、开放标签、盲法终点 (PROBE) 研究。

背景血管紧张素转换酶（ACE）抑制剂和血管紧张素受体阻滞剂（ARB）可预防正常白蛋白尿的2型糖尿病患者的微量白蛋白尿。我们评估了与 2 种药物联合治疗是否可以比 ACEI 或 ARB 单药治疗更好地预防微量白蛋白尿。方法和发现 VARIETY 是一项前瞻性、随机、开放标签、盲法终点 (PROBE) 试验，评估在相似的血压 (BP) 控制下，在 612 例高正常值的 2 型糖尿病患者中，贝那普利（10 毫克/天）和缬沙坦（160 毫克/天）联合治疗比贝那普利（20 毫克/天）或缬沙坦（320 毫克/天）单药治疗更有效地预防微量白蛋白尿2007 年 7 月至 2013 年 4 月期间，Istituto di Ricerche Farmacologiche Mario Negri IRCCS 和意大利的 8 个糖尿病或肾脏病学单位包括了蛋白尿。进展为微量白蛋白尿的时间是主要结果。分析是意向治疗。各组之间的基线特征相似。在中位 [四分位距，IQR] 66 [42 至 83] 个月的随访期间，联合治疗组 53 名患者 (27.0%)、贝那普利组 57 名 (28.1%) 和缬沙坦组 64 名 (31.8%) 患者出现微量白蛋白尿。使用加速失效时间模型，估计加速因子为 1.410（95% CI：0.806 到 2。467，P = 0.229）贝那普利与联合治疗相比，贝那普利与缬沙坦相比为 0.799（95% CI：0.422 至 1.514，P = 0.492），1.665（95% CI：1.007 至 P = 2.70）缬沙坦与联合治疗相比。调整预定义的混杂因素后，估计加速因素的组间差异不显着。各组的血压控制相似。所有治疗均安全且耐受性良好，联合治疗组的高钾血症和低血压略高。主要研究限制是纳入时的蛋白尿低于预期。结论 研究治疗的风险/收益概况是相似的。与贝那普利或缬沙坦单药治疗相比，不推荐使用双肾素-血管紧张素系统 (RAS) 阻断剂来预防正常白蛋白尿的 2 型糖尿病患者的微量白蛋白尿。试验注册 EudraCT 2006-005954-62；ClinicalTrials.gov NCT00503152。