Europace

Europace 2003 5(1):71-75; doi:10.1053/eupc.2002.0284
© 2003 by European Society of Cardiology

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Prevention of Syncope Trial (POST): a randomized clinical trial of beta blockers in the prevention of vasovagal syncope

Rationale and study design

R. Sheldon¹, S. Rose¹, S. Connolly² on behalf of the POST investigators³

¹Cardiovascular Research Group, University of Calgary Calgary, Alberta, Canada; ²McMaster University Hamilton, Ontario, Canada; ³The POST investigators are listed herein

BACKGROUND: Few therapies for vasovagal syncope have been proven effective. A large, placebo-controlled clinical trial of beta-blockers is needed.

STRUCTURE OF STUDY: The Prevention of Syncope Trial (POST) is a multicentre, randomized, placebo-controlled, study of metoprolol in the prevention of vasovagal syncope. The primary hypothesis is that beta-blockers will increase the time to the first recurrence of syncope when compared with placebo. Patients will be randomized 1:1 to receive metoprolol or placebo, and followed for 1 year. The primary endpoint is the time to first syncope recurrence, and secondary endpoints include syncope frequency, presyncope, and quality of life.

INCLUSION AND EXCLUSION CRITERIA: Patients are eligible if they have a positive tilt test and 3 syncopal spells preceding the tilt test. They are excluded if they have seizures or other causes of syncope; important heart disease; a contraindication to or need for beta blockers; a permanent pacemaker; a major noncardiovascular disease; or previous use of beta blockers at a dose greater than the equivalent of metoprolol 25 mg twice daily for the purpose of suppressing vasovagal syncope.

POWER CALCULATIONS: We assume a 40% risk of syncope in the control arm, an absolute reduction of 20% by metoprolol, and a dropout of 20%. Entry of 220 patients will result in an 80% chance of reaching a positive conclusion about beta-blocker therapy with 2p=0·05.

Key Words: Vasovagal syncope, tilt table test, randomized clinical trial, quality of life, beta-blockers

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Correspondence: Dr Robert Sheldon, University of Calgary, Health Sciences Centre, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada. Tel.: (403) 220-8191; Fax: (403) 270-0313; E-mail: sheldon{at}ucalgary.ca

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[1] Chen LY, Shen WK, Mahoney DW, Jacobsen SJ, Rodeheffer RJ. Prevalence of self-reported syncope: An epidemiologic study from Olmsted County, MN. J Am Coll Cardiol 2002; 39: 114A–115A (Abstract).

[2] Sheldon RS, Rose S, Koshman ML. Comparison of patients with syncope of unknown cause having negative or positive tilt table tests. Am J Cardiol 1997; 80: 581–585.[CrossRef][Web of Science][Medline]

[3] Grimm W, Degenhardt M, Hoffmann J, Menz V, Wirths A, Maisch B. Syncope recurrence can be better predicted by history than by head-up tilt testing in untreated patients with suspected neurally mediated syncope. Eur Heart J 1997; 18: 1465–1469.[Abstract/Free Full Text]

[4] Linzer M, Pontinen M, Gold DT, Divine GW, Felder A, Brooks WB. Impairment of physical and psychosocial function in recurrent syncope. J Clin Epidemiol 1991; 44: 1037–1043.[CrossRef][Web of Science][Medline]

[5] Linzer M, Gold DT, Pontinen M, Divine GW, Felder A, Brooks WB. Recurrent syncope as a chronic disease: Preliminary validation of a disease-specific measure of functional impairment. J Gen Int Med 1994; 9: 181–186.[Web of Science][Medline]

[6] Rose S, Koshman ML, Spreng S, Sheldon RS. The relationship between health-related quality of life and frequency of spells in patients with syncope. J Clin Epi 2000; 53: 1209–1216.[CrossRef][Web of Science][Medline]

[7] Sheldon R, Koshman ML, Wilson W, Kieser T, Rose S. Effect of dual chamber pacing with automatic rate-drop sensing on recurrent neurally mediated syncope. Am J Cardiol 1988; 81: 158–162.

[8] Sheldon R, Rose S, Flanagan P, Koshman ML, Killam S. Risk factors for syncope recurrence after a positive tilt table test in patients with syncope. Circulation 1996; 93: 973–981.[Abstract/Free Full Text]

[9] Natale A, Geiger MJ, Maglio C, et al. Recurrence of neurocardiogenic syncope without pharmacologic interventions. Am J Cardiol 1996; 77: 1001–1003.[CrossRef][Web of Science][Medline]

[10] Cox MM, Perlman BA, Mayor MR, Silberstein TA, Levin E, Pringle L, Castellanos A, Myerburg R. Acute and long-termbeta-adrenergic blockade for patients with neurocardiogenic syncope. J Am Coll Cardiol 1995; 26: 1293–1298.[Abstract]

[11] Mahanonda N, Bhuripanyo K, Kangkagate C, Wansanit K, Kulchot B, Nademanee K, Chaithiraphan S. Randomized double-blind, placebo-controlled trial of oral atenolol in patients with unexplained syncope and positive upright tilt table test results. Am Heart J 1995; 130: 1250–1253.[CrossRef][Web of Science][Medline]

[12] Sheldon RS, Rose S, Flanagan P, Koshman ML, Killam S. Effect of beta-blockers on the time to first syncope recurrence in patients after a positive isoproterenol-tilt table test. Am J Cardiol 1996; 78: 536–539.[CrossRef][Web of Science][Medline]

[13] Madrid AH, Ortega J, Rebollo JG, Manzano JG, Segovia JG, Sanchez A, Pena G, Moro C. 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]

[14] Ventura R, Maas R, Zeidler D, Schoder V, Nienaber CA, Schuchert A, Meinertz T. A randomized and controlled pilot trial of beta-blockers for the treatment of recurrent syncope in patients with a positive or negative response to head-up tilt test. Pacing Clin Electrophysiol 2002; 25: 816–821.[CrossRef][Medline]

[15] Natale A, Newby KH, Dhala A, Akhtar M, Sra J. Response to beta blockers in patients with neurocardiogenic syncope: How to predict beneficial effects. J Cardiovasc Electrophysiol 1996; 7: 1154–1158.[Web of Science][Medline]

[16] Leor J, Rotstein Z, Vered Z, Kaplinsky E, Truman S, Eldar M. Absence of tachycardia during tilt test predicts failure of beta-blocker therapy in patients with neurocardiogenic syncope. Am Heart J 1994; 127: 1539–1543.[CrossRef][Web of Science][Medline]

[17] Klingenheben T, Kalusche D, Li Y, Schopperl M, Hohnloser SH. Changes in plasma epinephrine concentration and in heart rate during head-up tilt testing in patients with neurocardiogenic syncope: correlation with successful therapy with ß-receptor antagonists. J Cardiovasc Electrophysiol 1996; 7: 802–805.[Web of Science][Medline]

[18] Benditt DG, Ferguson DW, Grubb BP, Kapoor W, Kugler J, Lerman BB, Maloney JD, Raviele A, Ross B, Sutton R, Wolk MJ, Wood DL. Tilt table testing for assessing syncope. J Am Coll Cardiol 1996; 28: 263–275.[CrossRef][Web of Science][Medline]

[19] Morillo CA, Klein GJ, Zandri S, Yee R. Diagnostic accuracy of a low-dose isoproterenol head-up tilt protocol. Am Heart J 1995; 129: 901–906.[CrossRef][Web of Science][Medline]

[20] Sheldon RS and Koshman ML. A randomized study of tilt test angle in patients with undiagnosed syncope. Can J Cardiol 2001; 17: 1051–1057.[Web of Science][Medline]

[21] Sheldon RS and Killam S. Methodology of isoproterenol-tilt table testing in patients with syncope. J Am Coll Cardiol 1992; 19: 773–779.[Abstract]

[22] Malik P, Koshman ML, Sheldon R. Timing of first syncope recurrence predicts syncope frequency following a positive tilt table test. J Am Coll Cardiol 1997; 29: 1284–1289.[Abstract]

[23] Sheldon RS, Sexton E, Koshman ML. Usefulness of clinical factors in predicting outcomes of passive tilt tests in patients with syncope. Am J Cardiol 2000; 85: 360–364.[CrossRef][Web of Science][Medline]

[24] Sheldon RS and Rose S. Components of clinical trials for vasovagal syncope. Europace 2001; 3: 233–240.[Abstract/Free Full Text]

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This Article Abstract FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (8) Request Permissions Disclaimer Google Scholar Articles by Sheldon, R. Search for Related Content PubMed PubMed Citation Articles by Sheldon, R. Social Bookmarking          What's this?