title: Rationale for the Assessment of Metoprolol in the Prevention of Vasovagal Syncope in Aging Subjects Trial (POST5).
abstract: BACKGROUND
  Vasovagal syncope (VVS) is a common problem associated with a poor quality of life, which improves when syncope frequency is reduced. Effective pharmacological therapies for VVS are lacking. Metoprolol is a β-adrenergic receptor antagonist that is ineffective in younger patients, but may benefit older (≥40 years) VVS patients. Given the limited therapeutic options, a placebo-controlled clinical trial of metoprolol for the prevention of VVS in older patients is needed.
  
  
  METHODS
  The POST5 is a multicenter, international, randomized, placebo-controlled study of metoprolol in the prevention of VVS in patients ≥40 years old. The primary endpoint is the time to first recurrence of syncope. Patients will be randomized 1:1 to receive metoprolol 25 to 100 mg BID or matching placebo, and followed up for 1 year. Secondary end points include syncope frequency, presyncope, quality of life, and cost analysis. Primary analysis will be intention to treat, with a secondary on-treatment analysis.
  A sample size of 222, split equally between the groups achieves 85% power to detect a hazard rate of 0.3561 when the event rates are 50% and 30% in the placebo and metoprolol arms. Allowing for 10% dropout, we propose to enroll 248 patients.
  
  
  CONCLUSIONS
  This study will be the first adequately powered trial to determine whether metoprolol is effective in preventing VVS in patients ≥40 years. If effective, metoprolol may become the first line pharmacological therapy for these patients.
authors.affiliation: Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada; Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN. Electronic address: satish.raj@ucalgary.ca.
authors.forename: Satish R
authors.initials: SR
authors.lastname: Raj
authors.affiliation: Alberta Health Services, Calgary, AB, Canada.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Faris
authors.affiliation: Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Semeniuk
authors.affiliation: Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada.
authors.forename: Braden
authors.initials: B
authors.lastname: Manns
authors.affiliation: Heart Rhythm Services, Division of Cardiology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Krahn
authors.affiliation: McMaster University, Hamilton, ON, Canada.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Morillo
authors.affiliation: Cardiac Arrhythmia and Syncope Center, University of Minnesota, Minneapolis, MN.
authors.forename: David G
authors.initials: DG
authors.lastname: Benditt
authors.affiliation: Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sheldon
mesh_terms: D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000375:Aging; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage*; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D012008:Recurrence; D019462:Syncope, Vasovagal / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D008790:Metoprolol