Prospective evaluation of a two-step therapeutic strategy in neurocardiogenic syncope: midodrine as second line treatment in patients refractory to beta-blockers.

Pharmacological therapy of neurocardiogenic syncope is often limited by the relatively low response rate to such treatment. In particular, response to beta-blocker treatment has been reported to average 50%. Therefore, a two-step protocol, with metoprolol being the drug of first choice, was developed and prospectively evaluated in consecutive patients with a history of repeated syncopal attacks and a positive tilt table test indicative of neurocardiogenic syncope. Patients not responding to the beta-blocker were switched to the alpha-adrenoceptoragonist midodrine. Acute drug efficacy was assessed by repeated tilt table testing. The incidence of syncope recurrence rate was determined during a 7-month follow-up. In 16 of 30 (53%) patients, metoprolol was primarily effective; this was also the case in 7 of 11 patients receiving midodrine. Thus, the overall efficacy rate could be increased to 77% by the treatment protocol (P = 0.009, as compared to beta-blocker treatment alone). During follow-up, only 1 of 27 patients (4%) had a syncopal event. Thus, the two-step treatment protocol presented in this study proved to be safe and to improve significantly patients clinical symptoms, as well as results of repeated tilt table testing as compared to beta-blocker treatment alone.