Robert Sheldon1, Satish R Raj2, M Sarah Rose3, Carlos A Morillo4, Andrew D Krahn5, Eduardo Medina6, Mario Talajic7, Teresa Kus8, Colette M Seifer9, Malgorzata Lelonek10, Thomas Klingenheben11, Ratika Parkash12, Debbie Ritchie3, Maureen McRae3. 1. Division of Cardiology, Department of Cardiac Sciences, University of Calgary, Calgary, Canada. Electronic address: sheldon@ucalgary.ca. 2. Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee. 3. Division of Cardiology, Department of Cardiac Sciences, University of Calgary, Calgary, Canada. 4. Division of Cardiology, Department of Medicine, McMaster University, Hamilton, Canada. 5. Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, Canada. 6. Neurocardiology Department, CES University, Medellin, Colombia. 7. Division of Cardiology, Department of Medicine, University of Montreal, Montreal, Canada. 8. Department of Pharmacology, Universite de Montreal, Montreal, Canada. 9. Division of Cardiology, Department of Medicine, University of Manitoba, Winnipeg, Canada. 10. Department of Cardiology, Medical University of Lodz, Lodz, Poland. 11. Praxis für Kardiologie, JW Goethe University, Frankfurt, Germany. 12. Division of Cardiology, Department of Medicine, Dalhousie University, Halifax, Canada.
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 tofludrocortisone 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).
RCT Entities:
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).
Authors: Awaneesh Kumar; Keith Wright; Domingo E Uceda; Peter A Vasallo; Perry L Rabin; David Adams; Johnson Wong; Mithilesh Das; Shien-Fong Lin; Peng-Sheng Chen; Thomas H Everett Journal: Heart Rhythm Date: 2019-10-09 Impact factor: 6.343