Second Vasovagal Pacemaker Study (VPS II): rationale, design, results, and implications for practice and future clinical trials.

Vasovagal syncope causes substantial morbidity. Various medications have been studied with goals of reducing event-rates and improving quality of life. Results have been mixed, with few drugs demonstrating benefit. Bradycardia usually accompanies vasovagal syncope during positive tilt table tests, and is recorded in up to 50% of clinical syncopal spells documented on electrocardiographic loop recorders. These findings form the rationale for studies of the effectiveness of pacing in preventing vasovagal syncope. Three historically controlled trials of permanent pacing showed that 80-90% of patients had a marked symptomatic improvement, with 90-95% reductions in the number of expected syncopal spells. Subsequently three open-label trials randomized a total of 189 patients evenly to medical therapy or pacemakers in trials that used the proportion of patients with recurrent syncope as the primary outcome. They showed relative risk reductions of 80-87% in the paced patients. However these early studies were not blinded, raising concern about the possible role of a significant placebo effect. This issue was addressed in the recent Second Vasovagal Pacemaker Study (VPS II), in which 100 patients received pacemakers. They then were randomized to pacing with rate drop sensing, or sensing without pacing. The cumulative risk of syncope at 6 months was 40% for the control group and 31% for the actively paced group. The relative risk reduction in time to syncope with pacing was 30% (1 p = 0.14). The AHA/ACC guidelines about pacing and vasovagal syncope should be reassessed. Future clinical trials of therapies for vasovagal syncope should be randomized and placebo-controlled.