Effectiveness of midodrine treatment in patients with recurrent vasovagal syncope not responding to non-pharmacological treatment (STAND-trial)

Abstract

AIMS: Initial treatment of vasovagal syncope (VVS) consists of advising adequate fluid and salt intake, regular exercise, and physical counterpressure manoeuvres. Despite this treatment, up to 30% of patients continue to experience regular episodes of VVS. We investigated whether additional Midodrine treatment is effective in these patients. METHODS AND RESULTS: In our study, patients with at least three syncopal and/or severe pre-syncopal recurrences during non-pharmacological treatment were eligible to receive double-blind cross-over treatment starting either with Midodrine or placebo. Treatment periods lasted for 3 months with a wash-out period of 1 week in-between. At baseline and after each treatment period, we collected data about the recurrence of syncope and pre-syncope, side effects, and quality of life (QoL). Twenty-three patients (17% male, mean age 32) included in the cross-over trial received both Midodrine and placebo treatment. The proportion of patients who experienced syncopal and pre-syncopal recurrences did not differ significantly between Midodrine and placebo treatment (syncope: 48 vs. 65%, P= 0.22; pre-syncope: 74 vs. 78%, P> 0.99). The median number of syncopes and pre-syncopes per 3 months were also not significantly different during Midodrine and placebo treatment (0 vs. 1; P= 0.57; and 6 vs. 8; P= 0.90). The occurrence of side effects was similar during Midodrine and placebo treatment (48 vs. 57%; P= 0.75). Also, QoL did not differ significantly. CONCLUSION: Our findings indicate that additional Midodrine treatment is less effective in patients with VVS not responding to non-pharmacological treatment than reported as first-line treatment.