Reference: Ann Intern Med. 2021 Aug 3
Vasovagal syncope is a common cause of fainting that may lead to physical and mental trauma and impaired quality of life. Two clinical trials have suggested that midodrine, a vasoconstrictor, could be a new treatment for the prevention of recurrent vasovagal syncopes. However, one of these trials only evaluated a small number of children, while the other was not blinded and did not include a placebo arm. To overcome these limitations, the recently published POST 4 trial aimed at assessing the efficiency and the safety of midodrine in adult patients using a placebo-controlled, double-blinded approach.
One hundred thirty-eight adults with a mean age 32, no serious comorbidities and an average of 6 syncopal events in the previous year were randomized to receive midodrine or placebo for 12 months. Patients allocated to the midodrine group started treatment with one 5 mg midodrine tablet taken TID, with adjustments based on side effects. The final median dose was 7.5 mg TID. All patients were additionally provided with information on conservative measures aimed at preventing vasovagal syncope, including physical maneuvers and dietary advice emphasizing fluid and sodium intake.
Ninety patients (65%) completed their follow-up evaluation at 12 months. The proportion of patients with at least one syncopal episode during the follow-up period was 42% in those treated with midodrine and 61% in those who received placebo (p = 0.035). Patients treated with midodrine with at least one syncopal event had a similar total number of syncopal events compared with the placebo group. The time to the first syncopal event was also longer among patients who received midodrine compared with those who took the placebo (hazard ratio 0.59, 95% CI 0.37-0.96). Both groups exhibited a similar number of adverse events, the most common being paresthesia and piloerection (17.9% with midodrine vs. 12.1% with placebo) and headaches (9% vs. 7.6%).
The dropout rate (35%) and differential loss to follow up weaken this data significantly. If taken as true, however, the results would indicate that midodrine might be helpful for only a subset of patients who, for whatever unidentified physiologic reason, appear to respond to the medication. The fact that patients with at least one syncopal episode on midodrine had no difference in median episodes compared with the placebo group suggests that midodrine either prevented the syncopal events completely or had no effect, which may be due to different etiologies of the vasovagal symptoms. From a practice standpoint, patients should consider stopping midodrine if they experience a syncopal event during the treatment. As per usual, additional higher quality trials are needed to confirm these findings.
For more information, see the topic Vasovagal Syncope in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Vincent Lemaitre, PhD, Medical Writer at DynaMed. Edited by, Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Dan Randall, MD, Deputy Editor at DynaMed; Carina Brown, MD, Assistant Professor at Cone Health Family Medicine Residency; Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia and Clinical Editor at DynaMed; Nicole Jensen, MD, family physician at WholeHealth Medical; Tanya Tupper, RT(N), CNMT, PET, Senior Medical Writer at DynaMed; and Christine Fessenden, Editorial Operations Assistant at DynaMed.