Barnett Anthony H, Bain Stephen C, Bouter Paul, Karlberg Bengt, Madsbad Sten, Jervell Jak, Mustonen Jukka
Division of Medical Sciences, University of Birmingham and Birmingham Heartlands and Solihull National Health Service Trust (Teaching), Birmingham, United Kingdom.
N Engl J Med. 2004 Nov 4;351(19):1952-61. doi: 10.1056/NEJMoa042274. Epub 2004 Oct 31.
Few studies have directly compared the renoprotective effects of angiotensin II-receptor blockers and angiotensin-converting-enzyme (ACE) inhibitors in persons with type 2 diabetes.
In this prospective, multicenter, double-blind, five-year study, we randomly assigned 250 subjects with type 2 diabetes and early nephropathy to receive either the angiotensin II-receptor blocker telmisartan (80 mg daily, in 120 subjects) or the ACE inhibitor enalapril (20 mg daily, in 130 subjects). The primary end point was the change in the glomerular filtration rate (determined by measuring the plasma clearance of iohexol) between the baseline value and the last available value during the five-year treatment period. Secondary end points included the annual changes in the glomerular filtration rate, serum creatinine level, urinary albumin excretion, and blood pressure; the rates of end-stage renal disease and cardiovascular events; and the rate of death from all causes.
After five years, the change in the glomerular filtration rate was -17.5 ml per minute per 1.73 m2 (where the minus sign denotes a decrement) in the telmisartan-treated subjects, as compared with -15.0 ml per minute per 1.73 m2 in the enalapril-treated subjects; the treatment difference was thus -2.6 ml per minute per 1.73 m2 (95 percent confidence interval, -7.1 to 2.0 ml per minute per 1.73 m2)[corrected] The lower boundary of the confidence interval, in favor of enalapril, was greater than the predefined margin of -10.0 ml per minute per 1.73 m2, indicating that telmisartan was not inferior to enalapril. The effects of the two agents on the secondary end points were not significantly different after five years.
Telmisartan is not inferior to enalapril in providing long-term renoprotection in persons with type 2 diabetes. These findings do not necessarily apply to persons with more advanced nephropathy, but they support the clinical equivalence of angiotensin II-receptor blockers and ACE inhibitors in persons with conditions that place them at high risk for cardiovascular events.
很少有研究直接比较血管紧张素II受体阻滞剂和血管紧张素转换酶（ACE）抑制剂对2型糖尿病患者的肾脏保护作用。
在这项前瞻性、多中心、双盲、为期五年的研究中，我们将250例2型糖尿病早期肾病患者随机分为两组，分别接受血管紧张素II受体阻滞剂替米沙坦（每日80毫克，120例患者）或ACE抑制剂依那普利（每日20毫克，130例患者）治疗。主要终点是五年治疗期内肾小球滤过率（通过测量碘海醇的血浆清除率来确定）从基线值到最后一个可用值的变化。次要终点包括肾小球滤过率、血清肌酐水平、尿白蛋白排泄量和血压的年度变化；终末期肾病和心血管事件的发生率；以及全因死亡率。
五年后，替米沙坦治疗组患者的肾小球滤过率变化为每分钟每1.73平方米-17.5毫升（负号表示下降），依那普利治疗组为每分钟每1.73平方米-15.0毫升；因此治疗差异为每分钟每1.73平方米-2.6毫升（95%置信区间为每分钟每1.73平方米-7.1至2.0毫升）[已校正]。置信区间的下限有利于依那普利，大于预先定义的每分钟每1.73平方米-10.0毫升的界值，表明替米沙坦不劣于依那普利。五年后，两种药物对次要终点的影响无显著差异。
在为2型糖尿病患者提供长期肾脏保护方面，替米沙坦不劣于依那普利。这些发现不一定适用于肾病更严重的患者，但它们支持血管紧张素II受体阻滞剂和ACE抑制剂在心血管事件高危患者中的临床等效性。
