TY - JOUR
T1 - Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2
T2 - Higher recurrence of events under metoprolol
AU - Chockalingam, Priya
AU - Crotti, Lia
AU - Girardengo, Giulia
AU - Johnson, Jonathan N.
AU - Harris, Katy M.
AU - Van Der Heijden, Jeroen F.
AU - Hauer, Richard N.W.
AU - Beckmann, Britt M.
AU - Spazzolini, Carla
AU - Rordorf, Roberto
AU - Rydberg, Annika
AU - Clur, Sally Ann B.
AU - Fischer, Markus
AU - Van Den Heuvel, Freek
AU - Kääb, Stefan
AU - Blom, Nico A.
AU - Ackerman, Michael J.
AU - Schwartz, Peter J.
AU - Wilde, Arthur A.M.
N1 - Funding Information:
The research programs of Drs. Wilde and Kääb are supported by the Leducq program grant Alliance Against Sudden Cardiac Death (CVR05). Dr. Kääb has received funding from the German Bundesministerium (BMBF) and the German Cardiovascular Research Network (DZHK). The research programs of Drs. Schwartz and Crotti are supported by National Institutes of Health Grant HL083374 and Telethon Grant GGP09247 . Dr. Spazzolini's work is partly supported by Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy. Dr. Wilde is a member of the scientific advisory board of Transgenomics and Sorin. Dr. Ackerman is a consultant for Biotronik, Boston Scientific, Medtronic, PGx Health, St. Jude Medical, and Transgenomic; and has intellectual property in PGx Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
PY - 2012/11/13
Y1 - 2012/11/13
N2 - Objectives: The purpose of this study was to compare the efficacy of beta-blockers in congenital long QT syndrome (LQTS). Background: Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of commonly used beta-blockers are lacking, and clinicians generally assume they are equally effective. Methods: Electrocardiographic and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n = 134), metoprolol (n = 147), and nadolol (n = 101) were analyzed, excluding patients <1 year of age at beta-blocker initiation. Symptoms before therapy and the first breakthrough cardiac events (BCEs) were documented. Results: Patients (56% female, 27% symptomatic, heart rate 76 ± 16 beats/min, QTc 472 ± 46 ms) were started on beta-blocker therapy at a median age of 14 years (interquartile range: 8 to 32 years). The QTc shortening with propranolol was significantly greater than with other beta-blockers in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n = 101), 15 had BCEs (all syncopes). The QTc shortening was significantly less pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of the other 2 beta-blockers combined, after adjustment for genotype (odds ratio: 3.95, 95% confidence interval: 1.2 to 13.1, p = 0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients receiving metoprolol compared to propranolol/nadolol. Conclusions: Propranolol has a significantly better QTc shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective, whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used for symptomatic LQT1 and LQT2 patients.
AB - Objectives: The purpose of this study was to compare the efficacy of beta-blockers in congenital long QT syndrome (LQTS). Background: Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of commonly used beta-blockers are lacking, and clinicians generally assume they are equally effective. Methods: Electrocardiographic and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n = 134), metoprolol (n = 147), and nadolol (n = 101) were analyzed, excluding patients <1 year of age at beta-blocker initiation. Symptoms before therapy and the first breakthrough cardiac events (BCEs) were documented. Results: Patients (56% female, 27% symptomatic, heart rate 76 ± 16 beats/min, QTc 472 ± 46 ms) were started on beta-blocker therapy at a median age of 14 years (interquartile range: 8 to 32 years). The QTc shortening with propranolol was significantly greater than with other beta-blockers in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n = 101), 15 had BCEs (all syncopes). The QTc shortening was significantly less pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of the other 2 beta-blockers combined, after adjustment for genotype (odds ratio: 3.95, 95% confidence interval: 1.2 to 13.1, p = 0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients receiving metoprolol compared to propranolol/nadolol. Conclusions: Propranolol has a significantly better QTc shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective, whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used for symptomatic LQT1 and LQT2 patients.
KW - breakthrough cardiac events
KW - congenital long QT syndrome
KW - metoprolol
KW - nadolol
KW - propranolol
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U2 - 10.1016/j.jacc.2012.07.046
DO - 10.1016/j.jacc.2012.07.046
M3 - Article
C2 - 23083782
AN - SCOPUS:84868568919
SN - 0735-1097
VL - 60
SP - 2092
EP - 2099
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 20
ER -