BACKGROUND: Clinical trials of pacing for vasovagal syncope have shown conflicting results. We performed a meta-analysis to determine whether permanent pacemaker therapy prevents refractory vasovagal syncope. METHODS: Randomized trials comparing pacemaker therapy with medical therapy, usual care, placebo, or different pacing algorithms in the prevention of recurrent vasovagal syncope were considered. The primary endpoint was first recurrence of syncope. RESULTS: Nine randomized trials (2 double blind, 7 open label or single blind) were included. There was significant heterogeneity when all 9 trials were pooled (P=.0009 and I(2)=69.6%), reflecting methodological diversity in blinding and the nature of the control therapy. When pooled by trial methodology, heterogeneity was no longer apparent. Permanent pacing reduced the risk of recurrent syncope in unblinded studies (odds ratio [OR] 0.09, 95% confidence interval [CI], 0.04 to 0.22) and in studies comparing pacemaker algorithms (OR 0.04, 95% CI, 0.0 to 0.23). No effect was seen in double-blinded trials (OR 0.83, 95% CI, 0.41 to 1.70). Awareness that a permanent pacemaker was implanted and functional was associated with a significant 'expectation' effect, which itself reduced the risk of recurrent syncope (OR 0.16, 95% CI, 0.06 to 0.40, P=.0001). Results were similar when restricted to patients with a marked cardioinhibitory response on baseline tilt table testing. CONCLUSION: The results of small, preliminary trials have overestimated the treatment effect of pacemakers due to a lack of blinding of physicians and patients. Blinded trials suggest that the apparent response is due to a strong expectation response to pacing.
BACKGROUND: Clinical trials of pacing for vasovagal syncope have shown conflicting results. We performed a meta-analysis to determine whether permanent pacemaker therapy prevents refractory vasovagal syncope. METHODS: Randomized trials comparing pacemaker therapy with medical therapy, usual care, placebo, or different pacing algorithms in the prevention of recurrent vasovagal syncope were considered. The primary endpoint was first recurrence of syncope. RESULTS: Nine randomized trials (2 double blind, 7 open label or single blind) were included. There was significant heterogeneity when all 9 trials were pooled (P=.0009 and I(2)=69.6%), reflecting methodological diversity in blinding and the nature of the control therapy. When pooled by trial methodology, heterogeneity was no longer apparent. Permanent pacing reduced the risk of recurrent syncope in unblinded studies (odds ratio [OR] 0.09, 95% confidence interval [CI], 0.04 to 0.22) and in studies comparing pacemaker algorithms (OR 0.04, 95% CI, 0.0 to 0.23). No effect was seen in double-blinded trials (OR 0.83, 95% CI, 0.41 to 1.70). Awareness that a permanent pacemaker was implanted and functional was associated with a significant 'expectation' effect, which itself reduced the risk of recurrent syncope (OR 0.16, 95% CI, 0.06 to 0.40, P=.0001). Results were similar when restricted to patients with a marked cardioinhibitory response on baseline tilt table testing. CONCLUSION: The results of small, preliminary trials have overestimated the treatment effect of pacemakers due to a lack of blinding of physicians and patients. Blinded trials suggest that the apparent response is due to a strong expectation response to pacing.