Prevention of Syncope Trial 2 - POST 2


The goal of the trial was to assess the safety and efficacy of fludocortisone for patients with vasovagal syncope.

Contribution to the Literature: The POST 2 trial showed that fludocortisone does not reduce the risk of recurrent syncope at 12 months compared with placebo in patients with vasovagal syncope.

Study Design

Patients were randomized in a 1:1 open-label fashion to either oral fludocortisone 0.2 mg daily (n = 105) or placebo (n = 105).

  • Total number of enrollees: 210
  • Duration of follow-up: 364 days (median)
  • Mean patient age: 30 years
  • Female: 73%

Inclusion criteria:

  • Age ≥14 years
  • Score greater than -3 on Calgary Syncope Symptom Score
  • >2 lifetime syncopal spells

Exclusion criteria:

  • Other causes of syncope
  • Significant comorbidities (pacemaker, glaucoma, type 2 diabetes mellitus, hepatic disease, hypertension)
  • Clinical need for or contraindication to fludocortisone, previous use of fludocortisone
  • Postural tachycardia or orthostatic hypotension during 5-minute stand test

Other salient features/characteristics:

  • Lifetime spells: 18
  • Syncope frequency per year: 2.3
  • Mean systolic blood pressure: 113 mm Hg

Principal Findings:

The primary outcome, syncopal event rates at 12 months for fludocortisone vs. placebo, was 44% vs. 60.5% (hazard ratio [HR] 0.69, 95% confidence interval 0.46-1.03, p = 0.069).

Secondary outcomes for fludocortisone vs. placebo:

  • Restricting analysis only to syncope occurring after 2 weeks: HR 0.62, p = 0.029
  • Further restricting to those who achieved stabilized dose of 0.2 mg: HR 0.51, p = 0.019


The results of this trial indicate that fludocortisone does not reduce the risk of recurrent syncope at 12 months compared with placebo in patients with vasovagal syncope. Given the trend towards benefit though, it is unknown if a longer duration of follow-up in this trial or another trial with a larger sample size would show a significant benefit in favor of fludocortisone. This condition, although benign, is reasonably common in younger patients, particularly females. None of the other medications, such as midodrine or selective serotonin reuptake inhibitors, have convincingly been helpful in this patient population either.


Sheldon R, Raj SR, Rose MS, et al. Fludrocortisone for the Prevention of Vasovagal Syncope: A Randomized, Placebo-Controlled Trial. J Am Coll Cardiol 2016;68:1-9.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Arrhythmias, Cardiac, Fludrocortisone, Midodrine, Primary Prevention, Risk Reduction Behavior, Serotonin Uptake Inhibitors, Syncope, Syncope, Vasovagal, Systole

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