Vasovagal syncope: a prospective, randomized, crossover evaluation of the effect of propranolol, nadolol and placebo on syncope recurrence and patients’ well-being

Objectives We sought to assess the relative therapeutic efficacy of propranolol, nadolol and placebo in recurrent vasovagal syncope (VVS). Background Central and peripheral mechanisms have been implicated in the pathogenesis of VVS. Propranolol, nadolol and placebo have different sites of action on central and/or peripheral mechanisms. It has not yet been clarified whether one of the aforementioned treatments is more efficient than the others in reducing clinical episodes and exerting a beneficial effect on patients’ well-being. Methods We studied 30 consecutive patients with recurrent VVS and a positive head-up tilt test. All were serially and randomly assigned to propranolol, nadolol or placebo. Therapy with each drug lasted three months. On the day of drug crossover, patients reported the total number of syncopal and presyncopal attacks during the previous period. They also gave a general assessment of their quality of life, taking into account: 1) symptom recurrence; 2) drug side effects; and 3) their personal well-being during therapy (scale 0 to 4: 0 = very bad/discontinuation; 1 = bad; 2 = good; 3 = very good; 4 = excellent). At the end of the nine-month follow-up period, they reported whether they preferred a specific treatment over the others. Results Spontaneous syncopal and presyncopal episode recurrence during each three-month follow-up period was reduced by all drugs tested (analysis of variance [ANOVA]: CHI-SQUARE = 67.4, p < 0.0001 for syncopal attacks; CHI-SQUARE = 60.1, p < 0.0001 for presyncopal attacks) No differences were observed in the recurrence of syncope and presyncope among the three drugs. All drugs improved the patients’ well-being (ANOVA: CHI-SQUARE = 61.9, p < 0.0001). Conclusions Propranolol, nadolol and placebo are equally effective treatments in VVS, as demonstrated by a reduction in the recurrence of syncope and presyncope, as well as an improvement in the patients’ well-being.