Long-term comparison between perindopril and nifedipine in normotensive patients with type 1 diabetes and microalbuminuria.
The aim of this study is to compare the efficacy of an angiotensin-converting enzyme inhibitor with a dihydropyridine calcium channel blocker in preventing progression to macroalbuminuria and/or a decline in renal function in normotensive patients with type 1 diabetes and microalbuminuria. Forty-two patients were randomized to treatment with either perindopril, slow-release nifedipine, or placebo. In the first 3 months, drug dosage was titrated to achieve a decrease in diastolic blood pressure of at least 5 mm HG: Thirty-three patients had a minimum of 24 months' data, and 25 patients were followed up beyond 36 months (mean, 67 +/- 4 months). Patients were studied every 3 months and at the end of the treatment period; those who remained normotensive discontinued therapy and were followed up for an additional 3 months. Baseline geometric mean albumin excretion rates (AERs) were as follows: perindopril, 66 microg/min; nifedipine, 59 microg/min; and placebo, 66 microg/min. During the first 3 years, 7 of the perindopril-treated but none of the placebo or nifedipine-treated patients reverted to normoalbuminuria (P < 0.01). Median AERs at 3 years of treatment in each group were 23 microg/min for perindopril, 122 microg/min for nifedipine, and 112 microg/min for placebo patients (P < 0.01). In patients with more than 3 years' follow-up, median AERs decreased by 45% in the first year and then stabilized in the perindopril group, but increased by 17.6% in the nifedipine group and 27.6% in the placebo group (P < 0.03) in the first year, then increased progressively. In these same patients, there was a significant decline in glomerular filtration rate in the nifedipine group (-7.8 +/- 1.8 mL/min/1.73 m(2)/y), but not in the other two groups (perindopril, -1.0 +/- 1.2 mL/min/1.73 m(2)/y; placebo, -1.3 +/- 1.1 mL/min/1.73 m(2)/y; P = 0.004). At the end of the study, cessation of treatment for 3 months was associated with a doubling of AERs in the perindopril-treated group, but no change in the other two groups (P < 0.001). In conclusion, long-term perindopril therapy is more effective than nifedipine or placebo in delaying the progression of diabetic nephropathy and reducing AER to the normoalbuminuric range (<20 microg/min) in normotensive patients with type 1 diabetes and microalbuminuria.
Jerums
G
G
Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg 3084, VIC, Australia. endo@austin.unimelb.edu.au
Allen
T J
TJ
Campbell
D J
DJ
Cooper
M E
ME
Gilbert
R E
RE
Hammond
J J
JJ
Raffaele
J
J
Tsalamandris
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000517:prevention & control*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000652:urine; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use*; D020913:Perindopril / Q000627:therapeutic use*; D011446:Prospective Studies; D013223:Statistics as Topic
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D009543:Nifedipine; D020913:Perindopril