Angiotensin-Receptor Blockade versus ConvertingEnzyme Inhibition in Type 2 Diabetes and Nephropathy
Anthony H. Barnett, M.D., Stephen C. Bain, M.D., Paul Bouter, Ph.D., Bengt Karlberg, M.D., Sten Madsbad, M.D., Jak Jervell, Ph.D., Jukka Mustonen, Ph.D., for the Diabetics Exposed to Telmisartan and Enalapril Study Group
Background Few studies have directly compared the renoprotectiveeffects of angiotensin IIreceptor blockers and angiotensin-convertingenzyme(ACE) inhibitors in persons with type 2 diabetes.
Methods In this prospective, multicenter, double-blind, five-yearstudy, we randomly assigned 250 subjects with type 2 diabetesand early nephropathy to receive either the angiotensin IIreceptorblocker telmisartan (80 mg daily, in 120 subjects) or the ACEinhibitor enalapril (20 mg daily, in 130 subjects). The primaryend point was the change in the glomerular filtration rate (determinedby measuring the plasma clearance of iohexol) between the baselinevalue and the last available value during the five-year treatmentperiod. Secondary end points included the annual changes inthe glomerular filtration rate, serum creatinine level, urinaryalbumin excretion, and blood pressure; the rates of end-stagerenal disease and cardiovascular events; and the rate of deathfrom all causes.
Results After five years, the change in the glomerular filtrationrate was 17.9 ml per minute per 1.73 m2 of body-surfacearea, where the minus sign denotes a decrement, with telmisartan(in 103 subjects), as compared with 14.9 ml per minuteper 1.73 m2 with enalapril (in 113 subjects), for a treatmentdifference of 3.0 ml per minute per 1.73 m2 (95 percentconfidence interval, 7.6 to 1.6 ml per minute per 1.73m2). The lower boundary of the confidence interval, in favorof enalapril, was greater than the predefined margin of 10.0ml per minute per 1.73 m2, indicating that telmisartan was notinferior to enalapril. The effects of the two agents on thesecondary end points were not significantly different afterfive years.
Conclusions Telmisartan is not inferior to enalapril in providinglong-term renoprotection in persons with type 2 diabetes. Thesefindings do not necessarily apply to persons with more advancednephropathy, but they support the clinical equivalence of angiotensinIIreceptor blockers and ACE inhibitors in persons withconditions that place them at high risk for cardiovascular events.
Source Information
From the Division of Medical Sciences, University of Birmingham and Birmingham Heartlands and Solihull National Health Service Trust (Teaching), Birmingham, United Kingdom (A.H.B., S.C.B.); the Department of Internal Medicine, Bosch Medicentre, Den Bosch, the Netherlands (P.B.); University Hospital, Linköping, Linköping, Sweden (B.K.); the Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark (S.M.); University Hospital of Oslo, Oslo (J.J.); and the Department of Internal Medicine, Tampere University Hospital, Tampere, Finland (J.M.).
Address reprint requests to Dr. Barnett at the Undergraduate Center, Birmingham Heartlands Hospital, Bordesley Green E., Birmingham B9 5SS, United Kingdom, or at anthony.barnett{at}heartsol.wmids.nhs.uk.
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