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.
Bibliographical noteFunding Information:
The POST 2 trial was supported by an Open Competition Operating Grant from the Canadian Institutes for Health Research, Ottawa, Canada. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Shire Pharmaceuticals provided placebo. Dr. Raj is a consultant for Lundbeck Pharmaceuticals, Medtronic, and GE Healthcare; and has received research funding from GE Healthcare. Dr. Morillo has received grants from Bayer, Boston Scientific, and Pfizer/BMS; is on the Advisory Board of Boston Scientific; and has been on speaker tours for Bayer, Boehringer Ingelheim, and Medtronic. Dr. Krahn has received research support from Medtronic and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Investigators in the POST 2 are listed in the Acknowledgments.
© 2016 American College of Cardiology Foundation.