Fludrocortisone Flops for Vasovagal Syncope: POST 2

Shelley Wood

October 28, 2011

October 28, 2011 (Vancouver, British Columbia) — Fludrocortisone (Florinef, Bristol-Myers Squibb) is of no benefit in reducing episodes of moderate to severe vasovagal syncope, results of the Prevention of Syncope Trial 2 (POST 2) show.

Presenting the results during a late-breaking clinical trial at the Canadian Cardiovascular Congress 2011 earlier this week, Dr Robert Sheldon (University of Calgary, AB) reminded his audience that vasovagal syncope is "incredibly common — as common in our emergency wards as atrial fibrillation, leading to a lot of hospital admissions and a lot of CT scans because the neurologists won't learn."

Dr Robert Sheldon

The great hope, he said, is for a drug therapy that would reduce syncope recurrence.

"Canada has demolished pacemakers and we've demolished beta blockers in this setting, so we set our targets on Florinef, our second-to-last great hope."

POST 2 — which Sheldon described as a trial first planned 20 years ago, which took seven years to complete — was conducted at 17 centers in Canada, the US, Poland, and Columbia. The trial enrolled 210 subjects, most of them young women in their late 20s and early 30s who had experienced anywhere from two to 15 syncope episodes in the past year, with a mean of three to four.

"This is a bad bunch that everybody would try to treat," Sheldon said. Many of the young patients, however, declined to participate in a trial of a drug for their problem. "It's an interesting group — this isn't 80-year-olds with atrial fibrillation. This is 30-year-olds who faint."

Patients were randomized 1:1 to either fludrocortisone (0.05-0.2 mg daily) or matching placebo for 12 months.

After one year, the syncope rate was numerically lower in the fludrocortisone group in both the intention-to-treat and on-treatment analyses, but the difference was not statistically significant. Anticipating a question he might get during the Q&A, Sheldon said it was highly unlikely that the trial had simply not had adequate power to detect a "clinically significant" benefit.

I actually think this is a crummy drug that doesn't work very well.

 

"Everyone is going to say, well, did you miss something? And the answer is, I don't think we did. I actually think this is a crummy drug that doesn't work very well. If you look at the 40% relative risk reduction that we originally specified, the chance of our having missed that based on the confidence intervals, it's right at the bottom, so it's really unlikely that we missed that. If you look even at a 33% relative risk reduction, which is beginning to be in the range that some people might use to treat these people, again, I don't think we missed anything."

Adverse events, however, were minor and rare, occurring in just 16 patients.

The bottom line is that fludrocortisone "does not provide a statistically significant benefit in preventing the first recurrence of vasovagal syncope and is unlikely to provide a clinically significant benefit," Sheldon concluded.

On the plus side, he added, "we got the right population," which is a good thing, since investigators are moving ahead this month with POST 4, looking at midodrine — the "last" great hope in terms of a pharmacological intervention in moderate to severe vasovagal syncope.

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