title: Rationale and design of the GISSI-Atrial Fibrillation Trial: a randomized, prospective, multicentre study on the use of valsartan, an angiotensin II AT1-receptor blocker, in the prevention of atrial fibrillation recurrence.
abstract: BACKGROUND
  The possibility of preventing atrial fibrillation recurrence with anti-arrhythmic agents is very limited, given the discouraging results obtained with current drugs in many patients. Data from experimental studies suggest that angiotensin II AT1-receptor blockers can influence atrial remodelling, a key factor in atrial fibrillation initiation and maintenance. Moreover, some preliminary clinical data show that angiotensin II AT1 -receptor blockers can prevent atrial fibrillation episodes. The GISSI-Atrial Fibrillation (AF) trial is a randomized, prospective, parallel group, placebo-controlled, multicentre study designed to test whether angiotensin II AT1-receptor blockers can reduce atrial fibrillation recurrence.
  
  
  OBJECTIVE
  The primary objective of the study is to demonstrate that, in patients with a history of recent atrial fibrillation who are treated with the best recommended therapies, the addition of the angiotensin II AT1-receptor blocker valsartan (titrated up to 320 mg) is superior to placebo in reducing atrial fibrillation recurrence. A substudy will analyse the effect of valsartan on left atrial dimensions and on neurohormones. The study population consists of patients with symptomatic atrial fibrillation (at least two electrocardiogram documented atrial fibrillation episodes in the previous 6 months or successful cardioversion in the last 2 weeks) with underlying cardiovascular diseases or comorbidities. With approximately 100 centres participating in Italy, a total of 1402 patients are randomized in a 1 : 1 ratio to receive valsartan or placebo. The enrolment period will last 12 months and the patients will be followed for 12 months from study entry.
  
  
  CONCLUSIONS
  The GISSI-AF is the largest trial aimed at assessing the role of angiotensin receptor blockade in reducing the recurrence of atrial fibrillation and its possible mechanisms of action in terms of its effects on atrium remodelling and neurohormones.
authors.affiliation: Department of Cardiology, S. Chiara Hospital, Trento, Italy. centro_studi@anmco.it
authors.forename: Marcello
authors.initials: M
authors.lastname: Disertori
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.forename: Aldo Pietro
authors.initials: AP
authors.lastname: Maggioni
authors.forename: Pietro
authors.initials: P
authors.lastname: Delise
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Pasquale
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Franzosi
authors.forename: Lidia
authors.initials: L
authors.lastname: Staszewsky
authors.forename: Gianni
authors.initials: G
authors.lastname: Tognoni
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000517:prevention & control*; D004311:Double-Blind Method; D004452:Echocardiography; D006801:Humans; D007558:Italy; D011446:Prospective Studies; D012008:Recurrence; D012107:Research Design; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine