CLINICAL QUESTION

Is midodrine an effective treatment for recurrent vasovagal syncope?

EVIDENCE-BASED ANSWER

Midodrine can treat recurrent vasovagal syncope in adults and children. It reduces the recurrence rate by at least 30% compared with placebo (number needed to treat [NNT] = 6). (Strength of Recommendation [SOR]: A, systematic review and meta-analysis of randomized controlled trials [RCTs].) Midodrine may also delay syncope recurrence compared with placebo. (SOR: B, single RCT.) A guideline from three cardiology organizations recommends midodrine as a reasonable treatment option for adults and children with recurrent vasovagal syncope without a history of hypertension, heart failure, or urinary retention. (SOR: B, evidence-based guideline.)

EVIDENCE SUMMARY

A 2022 systematic review and meta-analysis of seven placebo-controlled RCTs (n = 319) evaluated midodrine for the treatment of recurrent vasovagal syncope.¹ Studies included in the systematic review were from Canada (one trial; n = 133), the United States (two trials; n = 83), China (two trials; n = 70), the Netherlands (one trial; n = 23), and the United Kingdom (one trial; n = 16). Patients had a mean age of 33 years and 69% were female; two trials (n = 70) evaluated children with a mean age of 11 years. Patients had at least two spontaneous syncopal episodes within 1 year of study enrollment. The daily midodrine dosage ranged from 2.5 to 30 mg administered orally as a single or repeated dose for up to 1 year (median duration = 6 months). Three trials (n = 131) were open label. The primary outcome was syncope (i.e., brief and complete loss of consciousness) observed during a tilt-table test or reported by a patient at any time during the trial. Compared with placebo, midodrine decreased the risk of tilt-table test syncope by 63% (four trials; n = 98; relative risk [RR] = 0.37; 95% CI, 0.23 to 0.59; NNT = 3) and patient-reported syncope by 49% (five trials; n = 287; RR = 0.51; 95% CI, 0.34 to 0.79; NNT = 4). In subgroup analyses of double-blind RCTs, midodrine reduced tilt-table test syncope by 61% (two trials; n = 28; RR = 0.39; 95% CI, 0.21 to 0.70; NNT = 2) and patient-reported syncope by 30% (two trials; n = 156; RR = 0.7; 95% CI, 0.53 to 0.94; NNT = 6). Heterogeneity was low in pooled analyses tilt-table test outcomes and subgroup analyses of patient-reported syncope in double-blind RCTs. However, there was moderate heterogeneity in meta-analyses of patient-reported syncope that combined blinded and unblinded studies. Other limitations included an unclear risk of selection bias and a high risk of performance bias due to the lack of information on randomization methods in the three unblinded trials.