title: Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension: results from the PREVER-treatment randomized trial.
abstract: OBJECTIVE
  To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of stage I hypertension.
  
  
  METHODS
  In a randomized, double-blind, controlled trial, 655 participants were followed for 18 months in 21 Brazilian academic centers. Trial participants were adult volunteers aged 30-70 years with stage I hypertension (BP 140-159 or 90-99 mmHg) following 3 months of a lifestyle intervention. Participants were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 333) or 50 mg of losartan (N = 322). If BP remained uncontrolled after 3 months, study medication dose was doubled, and if uncontrolled after 6 months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg twice daily) were added as open-label drugs in a progressive fashion. At the end of follow-up, 609 (93%) participants were evaluated.
  
  
  RESULTS
  The difference in SBP during 18 months of follow-up was 2.3 (95% confidence interval: 1.2 to 3.3) mmHg favoring chlorthalidone/amiloride. Compared with those randomized to diuretic, more participants allocated to losartan had their initial dose doubled and more of them used add-on antihypertensive medication. Levels of blood glucose, glycosilated hemoglobin, and incidence of diabetes were no different between the two treatment groups. Serum potassium was lower and serum cholesterol was higher in the diuretic arm. Microalbuminuria tended to be higher in patients with diabetes allocated to losartan (28.5 ± 40.4 versus 16.2 ± 26.7 mg, P = 0.09).
  
  
  CONCLUSIONS
  Treatment with a combination of chlorthalidone and amiloride compared with losartan yielded a greater reduction in BP.
  
  
  BACKGROUND
  NCT00971165.
authors.affiliation: aHospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rio Grande do SulbHospital Universitário Júlio Müller - Universidade Federal de Mato Grosso, Mato GrossocFaculdade de Medicina São José do Rio Preto, São PaulodDepartment of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USAeFaculdade de Medicina Hospital São Lucas, PUCRSfHospital Universitário Walter Cantídio, Universidade Federal do CearágInstituto do Coração, Faculdade de Medicina, Universidade de São PaulohFaculdade de Ciências Farmacêuticas, USP Ribeirão Preto, São PauloiInstituto de Cardiologia, Rio Grande do SuljHospital Universitário, Universidade Federal do Maranhão, MaranhãokUniversidade Federal de Pernambuco, PernambucolUniversidade Federal de Pelotas, Rio Grande do SulmInstituto de Medicina Integral Prof Fernando Figueira, PernambuconUniversidade do Estado do Rio de Janeiro, Rio de JaneirooHospital das Clínicas da Universidade Federal de Minas Gerais, Minas GeraispHospital das Clínicas de Goiânia, Universidade Federal de Goiás, GoiásqFaculdade de Medicina de Botucatu, São PaulorHospital do Coração, AlagoassAnis Rassi Hospital, GoiástHospital Universitário Procape, PernambucouHospital Universitário Antônio Pedro, UFF, Rio de JaneirovFaculdade de Medicina de Ribeirão Preto, USP Ribeirão PretowInstituto de Pesquisa, Hospital do Coração, São Paulo, Brazil.
authors.forename: Flávio D
authors.initials: FD
authors.lastname: Fuchs
authors.forename: Luiz César N
authors.initials: LC
authors.lastname: Scala
authors.forename: José F
authors.initials: JF
authors.lastname: Vilela-Martin
authors.forename: Renato Bandeira
authors.initials: RB
authors.lastname: de Mello
authors.forename: Francisca
authors.initials: F
authors.lastname: Mosele
authors.forename: Paul K
authors.initials: PK
authors.lastname: Whelton
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Poli-de-Figueiredo
authors.forename: Paulo Ricardo
authors.initials: PR
authors.lastname: de Alencastro
authors.forename: Ricardo Pereira
authors.initials: RP
authors.lastname: E Silva
authors.forename: Miguel
authors.initials: M
authors.lastname: Gus
authors.forename: Luiz Aparecido
authors.initials: LA
authors.lastname: Bortolotto
authors.forename: Rosane
authors.initials: R
authors.lastname: Schlatter
authors.forename: Evandro José
authors.initials: EJ
authors.lastname: Cesarino
authors.forename: Iran
authors.initials: I
authors.lastname: Castro
authors.forename: José A Figueiredo
authors.initials: JA
authors.lastname: Neto
authors.forename: Hilton
authors.initials: H
authors.lastname: Chaves
authors.forename: André Avelino
authors.initials: AA
authors.lastname: Steffens
authors.forename: João Guilherme
authors.initials: JG
authors.lastname: Alves
authors.forename: Andréa Araujo
authors.initials: AA
authors.lastname: Brandão
authors.forename: Marcos R
authors.initials: MR
authors.lastname: de Sousa
authors.forename: Paulo Cesar
authors.initials: PC
authors.lastname: Jardim
authors.forename: Leila B
authors.initials: LB
authors.lastname: Moreira
authors.forename: Roberto Silva
authors.initials: RS
authors.lastname: Franco
authors.forename: Marco Mota
authors.initials: MM
authors.lastname: Gomes
authors.forename: Abrahão Afiune
authors.initials: AA
authors.lastname: Neto
authors.forename: Felipe Costa
authors.initials: FC
authors.lastname: Fuchs
authors.forename: Dario C Sobral
authors.initials: DC
authors.lastname: Filho
authors.forename: Antônio C
authors.initials: AC
authors.lastname: Nóbrega
authors.forename: Fernando
authors.initials: F
authors.lastname: Nobre
authors.forename: Otávio
authors.initials: O
authors.lastname: Berwanger
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Fuchs
mesh_terms: D000328:Adult; D000368:Aged; D000584:Amiloride / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002752:Chlorthalidone / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged
chemical_list: D000959:Antihypertensive Agents; D000584:Amiloride; D019808:Losartan; D002752:Chlorthalidone