title: The effects of amlodipine and enalapril on renal function in adults with hypertension and nondiabetic nephropathies: a 3-year, randomized, multicenter, double-blind, placebo-controlled study.
abstract: BACKGROUND
  Placebo-controlled trials have found that angiotensin-converting enzyme inhibitors (ACEIs) decrease proteinuria and slow the progression of nondiabetic nephropathies. However, head-to-head comparisons of ACEIs and calcium channel blockers (CCBs) have shown conflicting results. Indeed, a recent metaanalysis concluded that there is still uncertainty about the greater renoprotection seen with ACEIs or angiotensin II receptor blockers in nondiabetic patients with renal disease, particularly when using true glomerular filtration rate (GFR) as the primary outcome.
  
  
  OBJECTIVE
  The objective of this 3-year, randomized, multicenter, double-blind, placebo-controlled study was to compare true GFR decline (measured by yearly 51Cr-EDTA blood clearance) in nondiabetic, nonnephrotic adult hypertensive patients with estimated creatinine clearance of 20 to 60 mL/min.1.73 m(2), when randomized to a CCB (amlodipine, 5-10 mg/d) or an ACEI (enalapril, 5-20 mg/d).
  
  
  METHODS
  Patients (aged 18-80 years) entered a 4-week placebo run-in washout period and previous antihypertensive drugs were tapered off over 2 weeks. Add-on treatments were atenolol (50-100 mg/d), loop diuretics (furosemide, 20-500 mg/d or torsemide, 5-200 mg/d), alpha-blockers (prazosin, 2.5-5 mg/d or doxazosin, 1-16 mg/d), and centrally acting drugs (rilmenidine, 1-2 mg/d or methyldopa, 250-500 mg/d). The primary end point was true GFR measured by yearly (51)Cr-EDTA blood clearance. Secondary end points included a clinical composite of renal events and tolerability collected by a full clinical and laboratory evaluation at each study visit. Post hoc analyses for the change in GFR, proteinuria, and time to clinical events were also planned on baseline proteinuria subgroups (<1 and >or=1 g/d) before unblinding the database.
  
  
  RESULTS
  Three hundred eighteen patients entered the run-in period and 263 patients (156 men/107 women; mean age, 58 years) were randomized to receive either amlodipine (5 mg/d, n=132) or enalapril (5 mg/d, n=131). Blood pressure declined from 165/102 mm Hg to 138/84 mm Hg and 138/85 mm Hg with amlodipine and enalapril, respectively (no between-group significance). Only 20.8% of the patients randomized to ACEI treatment received diuretics at the last observation. No statistically significant difference was found between amlodipine and enalapril in GFR decline (-4.92 and -3.98 mL/min.1.73 m(2), respectively, at last observation) and composite secondary end point after a median follow-up of 2.9 years, including in the subgroup of patients with proteinuria >1 g/d at baseline. Protein excretion rate decreased significantly from baseline in patients taking enalapril plus diuretics (median -270 mg/d; P<0.001) but not in patients taking amlodipine plus diuretics (-25 mg/d at last observation).
  
  
  CONCLUSIONS
  In this cohort of nondiabetic, nonnephrotic hypertensive patients, no statistically significant difference in true GFR decline was found over 3 years between amlodipine-treated patients and enalapril-treated patients with main add-on treatment with ss-blockers, including in the subgroup of patients with proteinuria >1 g/d.
authors.affiliation: Pasteur Hospital, Université de Nice-Sofia Antipolis, Nice, France. esnault.v@chu-nice.fr
authors.forename: Vincent L M
authors.initials: VL
authors.lastname: Esnault
authors.forename: Edwina A
authors.initials: EA
authors.lastname: Brown
authors.forename: Eduard
authors.initials: E
authors.lastname: Apetrei
authors.forename: Jacques
authors.initials: J
authors.lastname: Bagon
authors.forename: Carlos
authors.initials: C
authors.lastname: Calvo
authors.forename: Rudolf
authors.initials: R
authors.lastname: DeChatel
authors.forename: Hallvard
authors.initials: H
authors.lastname: Holdaas
authors.forename: Silvester
authors.initials: S
authors.lastname: Krcmery
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Kobalava
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017311:Amlodipine / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D010919:Placebos; D017311:Amlodipine; D004656:Enalapril; D003404:Creatinine