Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol.
OBJECTIVE
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.
Department of Cardiology, Academic Medical Centre, Amsterdam, the Netherlands.
Priya
P
Chockalingam
Lia
L
Crotti
Giulia
G
Girardengo
Jonathan N
JN
Johnson
Katy M
KM
Harris
Jeroen F
JF
van der Heijden
Richard N W
RN
Hauer
Britt M
BM
Beckmann
Carla
C
Spazzolini
Roberto
R
Rordorf
Annika
A
Rydberg
Sally-Ann B
SA
Clur
Markus
M
Fischer
Freek
F
van den Heuvel
Stefan
S
Kääb
Nico A
NA
Blom
Michael J
MJ
Ackerman
Peter J
PJ
Schwartz
Arthur A M
AA
Wilde
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D002648:Child; D018572:Disease-Free Survival; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D009248:Nadolol / Q000494:pharmacology / Q000627:therapeutic use*; D011379:Prognosis; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use*; D055502:Secondary Prevention; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
D000319:Adrenergic beta-Antagonists; D009248:Nadolol; D011433:Propranolol; D008790:Metoprolol