Fludrocortisone for the Prevention of Vasovagal Syncope: A Randomized, Placebo-Controlled Trial
Robert Sheldon, Satish R Raj, M Sarah Rose, Carlos A Morillo, Andrew D Krahn, Eduardo Medina, Mario Talajic, Teresa Kus, Colette M Seifer, Malgorzata Lelonek, Thomas Klingenheben, Ratika Parkash, Debbie Ritchie, Maureen McRae, POST 2 Investigators, R S Sheldon, S M Rose, D A Ritchie, M McCrae, C Morillo, V M Malcolm, A D Krahn, B Spindler, E Medina, M Talajic, T Kus, A Langlois, M Lelonek, S Raj, C Seifer, M Gardner, M Romeo, P Poirier, C Simpson, H Abdollah, J Reynolds, P Dorian, D Birnie, M Giuffre, D Gilligan, D Benditt, R S Sheldon, S R Raj, M S Rose, A Krahn, C Morillo, E Medina, Robert Sheldon, Satish R Raj, M Sarah Rose, Carlos A Morillo, Andrew D Krahn, Eduardo Medina, Mario Talajic, Teresa Kus, Colette M Seifer, Malgorzata Lelonek, Thomas Klingenheben, Ratika Parkash, Debbie Ritchie, Maureen McRae, POST 2 Investigators, R S Sheldon, S M Rose, D A Ritchie, M McCrae, C Morillo, V M Malcolm, A D Krahn, B Spindler, E Medina, M Talajic, T Kus, A Langlois, M Lelonek, S Raj, C Seifer, M Gardner, M Romeo, P Poirier, C Simpson, H Abdollah, J Reynolds, P Dorian, D Birnie, M Giuffre, D Gilligan, D Benditt, R S Sheldon, S R Raj, M S Rose, A Krahn, C Morillo, E Medina
Abstract
Background: There is limited evidence whether being on fludrocortisone prevents vasovagal syncope.
Objectives: The authors sought to determine whether treatment with fludrocortisone reduces the proportion of patients with recurrent vasovagal syncope by at least 40%, representing a pre-specified minimal clinically important relative risk reduction.
Methods: The multicenter POST 2 (Prevention of Syncope Trial 2) was a randomized, placebo-controlled, double-blind trial that assessed the effects of fludrocortisone in vasovagal syncope over a 1-year treatment period. All patients had >2 syncopal spells and a Calgary Syncope Symptom Score >-3. Patients received either fludrocortisone or matching placebo at highest tolerated doses from 0.05 mg to 0.2 mg daily. The main outcome measure was the first recurrence of syncope.
Results: The authors randomized 210 patients (71% female, median age 30 years) with a median 15 syncopal spells over a median of 9 years equally to fludrocortisone or placebo. Of these, 96 patients had ≥1 syncope recurrences, and only 14 patients were lost to follow-up before syncope recurrence. There was a marginally nonsignificant reduction in syncope in the fludrocortisone group (hazard ratio [HR]: 0.69: 95% confidence interval [CI]: 0.46 to 1.03; p = 0.069). In a multivariable model, fludrocortisone significantly reduced the likelihood of syncope (HR: 0.63; 95% CI: 0.42 to 0.94; p = 0.024). When the analysis was restricted to outcomes after 2 weeks of dose stabilization, there was a significant benefit due to fludrocortisone (HR: 0.51; 95% CI: 0.28 to 0.89; p = 0.019).
Conclusions: The study did not meet its primary objective of demonstrating that fludrocortisone reduced the likelihood of vasovagal syncope by the specified risk reduction of 40%. The study demonstrated a significant effect after dose stabilization, and there were significant findings in post hoc multivariable and on-treatment analyses. (A randomised clinical trial of fludrocortisone for the prevention of vasovagal syncope; ISRCTN51802652; Prevention of Syncope Trial 2 [POST 2]; NCT00118482).
Keywords: faint; mineralocorticoid; recurrence; reflex.
Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Source: PubMed