title: Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER.
abstract: Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.
authors.affiliation: Medical Department M, Aarhus Komunehospital, Aarhus University Hospital, 8000 Aarhus, Denmark. carl.erik.mogensen@afdm.au.dk
authors.forename: Carl Erik
authors.initials: CE
authors.lastname: Mogensen
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Viberti
authors.forename: Serge
authors.initials: S
authors.lastname: Halimi
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.forename: Luis
authors.initials: L
authors.lastname: Ruilope
authors.forename: György
authors.initials: G
authors.lastname: Jermendy
authors.forename: Jiri
authors.initials: J
authors.lastname: Widimsky
authors.forename: Pinchas
authors.initials: P
authors.lastname: Sareli
authors.forename: Jan
authors.initials: J
authors.lastname: Taton
authors.forename: Juan
authors.initials: J
authors.lastname: Rull
authors.forename: Gürbüz
authors.initials: G
authors.lastname: Erdogan
authors.forename: Pieter W
authors.initials: PW
authors.lastname: De Leeuw
authors.forename: Arthur
authors.initials: A
authors.lastname: Ribeiro
authors.forename: Ramiro
authors.initials: R
authors.lastname: Sanchez
authors.forename: Rachid
authors.initials: R
authors.lastname: Mechmeche
authors.forename: John
authors.initials: J
authors.lastname: Nolan
authors.forename: Jana
authors.initials: J
authors.lastname: Sirotiakova
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hamani
authors.forename: André
authors.initials: A
authors.lastname: Scheen
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hess
authors.forename: Anton
authors.initials: A
authors.lastname: Luger
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000188:drug therapy* / Q000209:etiology / Q000652:urine; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003371:Cough / Q000139:chemically induced; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007190:Indapamide / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D004656:Enalapril; D007190:Indapamide; D020913:Perindopril