title: Effectiveness of Chlorthalidone Plus Amiloride for the Prevention of Hypertension: The PREVER-Prevention Randomized Clinical Trial.
abstract: Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension (PREVER-Prevention) trial aimed to evaluate the efficacy and safety of a low-dose diuretic for the prevention of hypertension and end-organ damage.
  
  
  
  This randomized, parallel, double-blind, placebo-controlled trial was conducted in 21 Brazilian academic medical centers. Participants with prehypertension who were aged 30 to 70 years and who did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new-onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms. The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with 358 allocated to placebo (hazard ratio 0.56, 95% CI 0.38-0.82), resulting in a cumulative incidence of 11.7% in the diuretic arm versus 19.5% in the placebo arm (P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow-Lyon voltage and voltage-duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02).
  
  
  
  A combination of low-dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension.
  
  
  
  URL: http://www.ClinicalTrials.gov, www.ensaiosclinicos.gov. Unique identifiers: NCT00970931, RBR-74rr6s.
authors.affiliation: Division of Cardiology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil sfuchs@hcpa.edu.br.
authors.forename: Sandra Costa
authors.initials: SC
authors.lastname: Fuchs
authors.affiliation: Faculdade de Medicina, Hospital São Lucas, PUCRS, Porto Alegre, Brazil.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Poli-de-Figueiredo
authors.affiliation: Hospital Universitário, Universidade Federal do Maranhão, São Luis, Brazil.
authors.forename: José A
authors.initials: JA
authors.lastname: Figueiredo Neto
authors.affiliation: Hospital Universitário Júlio Müller, Universidade Federal de Mato Grosso, Cuiabá, Brazil.
authors.forename: Luiz César N
authors.initials: LC
authors.lastname: Scala
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Whelton
authors.affiliation: Division of Cardiology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Francisca
authors.initials: F
authors.lastname: Mosele
authors.affiliation: Division of Cardiology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Renato Bandeira
authors.initials: RB
authors.lastname: de Mello
authors.affiliation: Faculdade de Medicina de São José do Rio Preto e Hospital de Base, São José do Rio Preto, Brazil.
authors.forename: José F
authors.initials: JF
authors.lastname: Vilela-Martin
authors.affiliation: Division of Cardiology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Leila B
authors.initials: LB
authors.lastname: Moreira
authors.affiliation: Universidade Federal de Pernambuco, Recife, Brazil.
authors.forename: Hilton
authors.initials: H
authors.lastname: Chaves
authors.affiliation: Hospital do Coração, Maceio, Brazil.
authors.forename: Marco
authors.initials: M
authors.lastname: Mota Gomes
authors.affiliation: Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Marcos R
authors.initials: MR
authors.lastname: de Sousa
authors.affiliation: Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, Brazil.
authors.forename: Ricardo Pereira E
authors.initials: RP
authors.lastname: Silva
authors.affiliation: Instituto de Cardiologia, Porto Alegre, Brazil.
authors.forename: Iran
authors.initials: I
authors.lastname: Castro
authors.affiliation: Faculdade de Ciências Farmacêuticas, USP Ribeirão Preto, Ribeirão Preto, Brazil.
authors.forename: Evandro José
authors.initials: EJ
authors.lastname: Cesarino
authors.affiliation: Hospital das Clínicas da Universidade Federal de Goiás, Goiania, Brazil.
authors.forename: Paulo Cesar
authors.initials: PC
authors.lastname: Jardim
authors.affiliation: Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brazil.
authors.forename: João Guilherme
authors.initials: JG
authors.lastname: Alves
authors.affiliation: Universidade Federal de Pelotas, Pelotas, Brazil.
authors.forename: André Avelino
authors.initials: AA
authors.lastname: Steffens
authors.affiliation: Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Andréa Araujo
authors.initials: AA
authors.lastname: Brandão
authors.affiliation: Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, Brazil.
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Consolim-Colombo
authors.affiliation: Division of Cardiology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Paulo Ricardo
authors.initials: PR
authors.lastname: de Alencastro
authors.affiliation: Hospital do Coração Anis Rassi, Goiania, Brazil.
authors.forename: Abrahão Afiune
authors.initials: AA
authors.lastname: Neto
authors.affiliation: Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niteroi, Brazil.
authors.forename: Antônio C
authors.initials: AC
authors.lastname: Nóbrega
authors.affiliation: Faculdade de Medicina de Botucatu, Botucatu, Brazil.
authors.forename: Roberto Silva
authors.initials: RS
authors.lastname: Franco
authors.affiliation: Hospital Universitário PROCAPE, Recife, Brazil.
authors.forename: Dario C
authors.initials: DC
authors.lastname: Sobral Filho
authors.affiliation: Division of Cardiology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Alexandro
authors.initials: A
authors.lastname: Bordignon
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, USP Ribeirão Preto, Ribeirão Preto, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Nobre
authors.affiliation: Division of Cardiology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Rosane
authors.initials: R
authors.lastname: Schlatter
authors.affiliation: Division of Cardiology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Miguel
authors.initials: M
authors.lastname: Gus
authors.affiliation: Division of Cardiology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Felipe C
authors.initials: FC
authors.lastname: Fuchs
authors.affiliation: Research Institute HCor Hospital do Coração, São Paulo, Brazil.
authors.forename: Otávio
authors.initials: O
authors.lastname: Berwanger
authors.affiliation: Division of Cardiology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Flávio D
authors.initials: FD
authors.lastname: Fuchs
mesh_terms: D000328:Adult; D000368:Aged; D000584:Amiloride / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002752:Chlorthalidone / Q000008:administration & dosage*; D004232:Diuretics / Q000008:administration & dosage*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000503:physiopathology / Q000517:prevention & control*; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D004232:Diuretics; D004338:Drug Combinations; D000584:Amiloride; D002752:Chlorthalidone
keywords: amiloride; blood pressure; cardiovascular diseases; chlorthalidone; clinical trials; diuretics; hypertension; left ventricular mass; microalbuminuria; potassium‐sparing antihypertensive agents; prehypertension; prevention