LETTER TO THE EDITOR
Beta-blockers in syncope: the jury is still out
Robert S. Sheldon, MD, PhDa,
Satish R. Raj, MDa,
Sarah Rose, PhDa and
Stuart J. Connolly, MDa
a Cardiovascular Research Group, University of Calgary, Room 1669, Health Sciences Centre, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada
sheldon{at}ucalgary.ca
Madrid et al. (1) are to be commended for assessing the efficacy of beta-blockers in neurocardiogenic syncope. Syncope is a common problem, and beta-blockers are commonly used to attempt to treat this disorder despite a paucity of randomized data.
Unfortunately, design limitations preclude this study from providing definitive answers as to the role of beta-blocking drugs in neurocardiogenic syncope. Previous papers have identified predictors of beta-blocker success, including the presence of tachycardia during the tilt table test, the need for isoproterenol to induce syncope, and an acute response to beta-blockers (2,3). By including a high percentage of tilt-negative patients (60%), the investigators may have inadvertently diluted a potential treatment effect. The researchers’ own data in their Figure 2 suggest a differential response to study medication based upon the result of the tilt table test. We agree with Madrid et al. (1) that tilt tests are not an ideal diagnostic modality, but a better tool is not presently available. We are now validating objective criteria quantitatively for the causes of syncope that make use of a structured history to diagnose neurocardiogenic syncope (1). Without such a tool, a positive tilt test remains the diagnostic standard.
In the accompanying editorial to the Madrid et al. (1) article, Dr. Sra (5) correctly points out that the assessment of therapy in neurocardiogenic syncope is difficult. A single recurrence of syncope is not an ideal end point due to symptom clusters and long symptom-free periods. This problem is not unique to syncope research; it is also seen in other disorders such as paroxysmal atrial fibrillation. We have previously reported that the time to first syncope recurrence after a positive tilt table test correlates very well with the frequency of syncope after a positive tilt table test (6). Time to first syncope recurrence is an appropriate end point for such studies, but it can be supplemented with other end points such as syncope burden and presyncope burden.
We agree with Dr. Sra (5) about the need for a large-scale multicenter trial to answer the question of beta-blockers for neurocardiogenic syncope. We are presently conducting a multinational, double-blind, placebo-controlled study of oral metoprolol in patients with at least three lifetime episodes of neurocardiogenic syncope and a positive head-up tilt table test. In the study, which is funded by the Canadian Institutes of Health Research, we are enrolling 220 patients, each of whom will be on blinded therapy for one year. The primary end point is time to first syncope recurrence, and secondary end points include the burden of syncope and presyncope, and the quality of life over the full year.
Madrid et al. (1) may eventually be found to be correct in concluding that atenolol specifically and beta-blockers in general are not effective in decreasing or delaying symptoms in patients with neurocardiogenic syncope. However, the final answer is not yet known. (4)
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References
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1. Madrid AH, Ortega J, Rebollo JG, et al. Lack of efficacy of atenolol for the prevention of neurally mediated syncope in a highly symptomatic population: a prospective, double-blind, randomized and placebo-controlled study. J Am Coll Cardiol. 2001;37:554–559[Abstract/Free Full Text]
2. Natale A, Newby KH, Dhala A, Akhtar M, Sra JS. Response to beta-blockers in patients with neurocardiogenic syncope: how to predict beneficial effects. J Cardiovasc Electrophysiol. 1996;7:1154–1158[Medline]
3. Leor J, Rotstein Z, Vered Z, Kaplinsky E, Truman S, Eldar M. Absence of tachycardia during tilt test predicts failure of ß-blocker therapy in patients with neurocardiogenic syncope. Am Heart J. 1994;127:1539–1543[CrossRef][Medline]
4. Sheldon R, Rose S, Ritchie D, Koshman ML, Frenneaux M, Connolly S. Anamnestic diagnostic criteria for tilt-positive vasovagal syncope. (abstr)Pacing Clin Electrophysiol. 2000;23:643
5. Sra JS. Can we assess the efficacy of therapy in neurocardiogenic syncope? J Am Coll Cardiol. 2001;37:560–561[Free Full Text]
6. Malik P, Koshman ML, Sheldon R. Timing of first recurrence of syncope predicts syncopal frequency after a positive tilt table test result. J Am Coll Cardiol. 1997;29:1284–1289[Abstract]
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