04 Jul Salt-Retaining Drug First Biomedical Treatment for Vasovagal Fainting

MedicalResearch.com Interview with:
Robert Sheldon, MD, PhD
Division of Cardiology, Department of Cardiac Sciences
University of Calgary, Calgary, Canada

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Vasovagal syncope is very common and more debilitating than most people appreciate. Probably up to 50% of people faint from this in their lives, making it the most common cardiovascular symptom. Around 15-20 years ago we had learned that the recurrence rates for vasovagal syncope were quite high, and that quality of life was correspondingly low. From the results of our earlier Vasovagal Pacemaker Study II and Prevention of Syncope Trial I (POST I) we knew that neither pacemakers nor beta blockers helped most patients with vasovagal syncope. However there was ample evidence that a reduction in venous return and cardiac preload were important early steps in the vasovagal cascade.

Florinef is a salt-retaining mineralocorticoid that is successful in treating orthostatic hypotension with tantalizing early evidence that it might prevent vasovagal syncope induced by tilt tests. We therefore set out to test whether it prevented vasovagal syncope in a randomized placebo-controlled clinical trial.

One important early part of designing a clinical trial is estimating the event rate in the untreated and treated arms. Based on our earlier work we could predict the untreated event rate but there were no data on which we could estimate the treated outcome rate. We therefore surveyed numerous colleagues for what they considered a Minimal Clinically Important Difference, and the answer was a 40% relative risk reduction. That is, to make fludrocortisone appealing to clinicians it should cause a relative risk reduction of 40%. We used this estimate to design the study.

There are two main conclusions.

• First, we studied the right population, people who would clearly be considered for active biomedical treatment. They had fainted 15-20 times in their lives and 3-4 times in the preceding year.
• Second, we found that fludrocortisone reduced syncope by 31%, and this narrowly missed conventional statistical significance. However when we adjusted for the first two weeks that were allotted for dose adjustment we found that fludrocortisone reduced syncope by up to 50% in people who were taking 0.2 mg daily. This is quite a low dose, deliberately picked to be safe in this young and predominantly female population.

MedicalResearch.com: What should readers take away from your report?

Response: Fludrocortisone is the first biomedical treatment with evidence of efficacy in many people, particularly young people, with vasovagal syncope.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: The search for effective treatments continues. POST III assesses the strategy of watchful waiting using an implantable loop recorder compared to empiric pacing in patients with syncope and bifascicular block; and POSTs IV and V are randomized clinical trials of midodrine and metoprolol for prevention of recurrent vasovagal syncope in predominantly younger and older populations.

MedicalResearch.com: Is there anything else you would like to add?

Response: Many parts of the world are very difficult environments for publicaly funded clinical research. Most centres in the United States have cost structures that are prohibitively (and often astonishingly) high, and the European Union buries studies such as POST 2 with regulations. By contrast, the United Kingdom and Canada, by design or by happenstance, are relatively hospitable environments. Finally, international agreements are necessary to ameliorate the spiraling insurance costs for drugs as well known and safe as beta blockers and fludrocortisone.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Sheldon R, Raj SR, Rose M, et al. Fludrocortisone for the Prevention of Vasovagal Syncope: A Randomized, Placebo-Controlled Trial. J Am Coll Cardiol. 2016;68(1):1-9. doi:10.1016/j.jacc.2016.04.030.

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Last Updated on July 4, 2016 by Marie Benz MD FAAD