Comparison of frequency of recurrent syncope after Beta-Blocker therapy versus conservative management for patients with vasovagal syncope

B blockers are among the first-line drugs traditionally used to treat vasovagal syncope (VVS).1 This practice has been based primarily on findings that spontaneous and tilt-table–induced faints generally are preceded by increased blood levels of catecholamines.2,3 Outcomes of -blocker therapy have been discordant among the few observational4 and randomized5–11 studies performed. In our study, the hypothesis was that -blocker therapy would be effective in preventing recurrent syncope in patients with VVS. To test this hypothesis, we compared the long-term response in consecutive patients given -blocker therapy with that in control patients treated conservatively. • • • All patients at the investigators’ institution who underwent tilt-table testing for evaluation of syncope between January 1996 and December 1998 were identified. Of the 816 patients, 463 (57%) had a positive response during tilt-table testing consistent with a vasovagal mechanism. Appropriate testing and consultation excluded other causes of syncope, such as conduction system disease, tachyarrhythmias, or neurologic or psychogenic causes. The diagnosis of VVS was confirmed by a consulting electrophysiologist who reviewed the patient’s clinical presentation and response to tilt-table testing. Of the 463 patients, follow-up information was available for 422 (91%). Of these, 163 patients were treated with -blockers and 75 (controls) were treated conservatively (defined as patient education, avoidance of dehydration, and no pharmacologic therapy). In our practice, all patients receive a consultation and educational pamphlet after syncope evaluation and confirmation of diagnosis. For patients with VVS, pathophysiologic mechanisms, warning symptoms, and techniques of preventing and aborting VVS are discussed in the educational material. Demographic and clinical data were obtained retrospectively from a centralized system of records from patients who underwent evaluation of syncope. Follow-up was conducted prospectively with a standardized survey (approved by the institutional review board) by mail or telephone. The end point was defined as recurrence of syncope. Recurrence of syncope was estimated by the Kaplan-Meier method in patients treated with blockers and in conservatively treated controls. Comparisons of the cumulative probability of recurrence between groups were completed using a 2-sample log-rank test. Predictors evaluated for the recurrent syncope end point are included in Table 1. Beta-blocker therapy was no longer significant after adjusting for the other predictors in the multivariate model (p 0.17). Univariate and multivariate associations of baseline variables with the cumulative probability of recurrent syncope were assessed using Cox proportional hazards models. Multivariate models were summarized in the form of point estimates and 95% confidence intervals (CIs) on the multivariate risk ratios (RRs). Two hundred thirty-eight patients received treatment for VVS; 163 were treated with blockers and 75 (controls) were treated conservatively. The mean SD follow-up for all subjects was 20 13 months. Patients treated with -blockers had a mean SD follow-up of 19 13 months; controls had a mean follow-up of 22 13 months (p 0.13). Table 1 lists the baseline characteristics of all subjects studied. The number of syncopal episodes in the year before evaluation was categorized as 0 to 1, 2 to 4, and 5 (Table 2). There was no statistically significant difference in the first 2 categories, but patients receiving blockers had a greater frequency of 5 episodes (p 0.04). Patients who received -blocker therapy were younger than those who were treated conservatively (p 0.004). Among patients who received blockers, 78 (48%) received metoprolol, 55 (34%) were on atenolol, 30 (18%) were on propranolol, and 1 (0.6%) patient received pindolol. Figure 1 shows survival free of recurrent VVS. Recurrent syncopal episodes occurred in 47 of 163 patients (29%) treated with blockers and 15 of 75 controls (20%) (RR 1.75, 95% CI 0.98 to 3.13, p 0.056). The probability of survival free of syncope at 2 years, as shown by Kaplan-Meier curve analyses, was 65% for patients treated with blockers and 80% for controls (p 0.056). Predictors of recurrent syncope were analyzed in a multivariate model. The positive predictors were 5 previous syncopal episodes, the presence of vertigo upon recovery, and the presence of co-morbid conditions (Table 3). In a large observational study of patients with VVS, we determined that recurrent syncope occurred in 47 of 163 patients (29%) treated with blockers From the Division of Cardiovascular Diseases and Internal Medicine and the Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. Dr. Shen was supported by grant P01NS32352 from the National Institutes of Health, Bethesda, Maryland, and a research grant from Medtronic, Minneapolis, Minnesota. Dr. Shen’s address is: Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905. E-mail: wshen@mayo.edu. Manuscript received October 21, 2002; revised manuscript received and accepted March 17, 2003.