title: A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double-blind controlled trial.
abstract: BACKGROUND
  Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted.
  
  
  METHODS
  This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution.
  
  
  CONCLUSIONS
  The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00971165.
authors.affiliation: Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. ffuchs@hcpa.ufrgs.br
authors.forename: Flávio D
authors.initials: FD
authors.lastname: Fuchs
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Fuchs
authors.forename: Leila B
authors.initials: LB
authors.lastname: Moreira
authors.forename: Miguel
authors.initials: M
authors.lastname: Gus
authors.forename: Antônio C
authors.initials: AC
authors.lastname: Nóbrega
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Poli-de-Figueiredo
authors.forename: Décio
authors.initials: D
authors.lastname: Mion
authors.forename: Luiz
authors.initials: L
authors.lastname: Bortolotto
authors.forename: Fernanda
authors.initials: F
authors.lastname: Consolim-Colombo
authors.forename: Fernando
authors.initials: F
authors.lastname: Nobre
authors.forename: Eduardo Barbosa
authors.initials: EB
authors.lastname: Coelho
authors.forename: José F
authors.initials: JF
authors.lastname: Vilela-Martin
authors.forename: Heitor
authors.initials: H
authors.lastname: Moreno
authors.forename: Evandro José
authors.initials: EJ
authors.lastname: Cesarino
authors.forename: Roberto
authors.initials: R
authors.lastname: Franco
authors.forename: Andréa Araujo
authors.initials: AA
authors.lastname: Brandão
authors.forename: Marcos R
authors.initials: MR
authors.lastname: de Sousa
authors.forename: Antônio Luiz Pinho
authors.initials: AL
authors.lastname: Ribeiro
authors.forename: Paulo Cesar
authors.initials: PC
authors.lastname: Jardim
authors.forename: Abrahão
authors.initials: A
authors.lastname: Afiune Neto
authors.forename: Luiz César N
authors.initials: LC
authors.lastname: Scala
authors.forename: Marco
authors.initials: M
authors.lastname: Mota
authors.forename: Hilton
authors.initials: H
authors.lastname: Chaves
authors.forename: João Guilherme
authors.initials: JG
authors.lastname: Alves
authors.forename: Dario C
authors.initials: DC
authors.lastname: Sobral Filho
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pereira e Silva
authors.forename: José A
authors.initials: JA
authors.lastname: Figueiredo Neto
authors.forename: Maria Cláudia
authors.initials: MC
authors.lastname: Irigoyen
authors.forename: Iran
authors.initials: I
authors.lastname: Castro
authors.forename: André Avelino
authors.initials: AA
authors.lastname: Steffens
authors.forename: Rosane
authors.initials: R
authors.lastname: Schlatter
authors.forename: Renato Bandeira
authors.initials: RB
authors.lastname: de Mello
authors.forename: Francisca
authors.initials: F
authors.lastname: Mosele
authors.forename: Flávia
authors.initials: F
authors.lastname: Ghizzoni
authors.forename: Otávio
authors.initials: O
authors.lastname: Berwanger
mesh_terms: D000328:Adult; D000368:Aged; D000584:Amiloride / Q000009:adverse effects / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D001938:Brazil; D002752:Chlorthalidone / Q000009:adverse effects / Q000627:therapeutic use*; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012107:Research Design; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D004232:Diuretics; D000584:Amiloride; D019808:Losartan; D002752:Chlorthalidone