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Efficacy of Different Beta-Blockers in the Treatment of Long QT Syndrome
Study Questions:
Do different beta-blockers vary in efficacy in reducing the risk of cardiac events in long QT syndrome (LQTS) and in genotype-positive LQT1 and LQT2 patients?
Methods:
Time-dependent Cox regression analyses were used to compare the efficacy of atenolol, metoprolol, propranolol, and nadolol on the risk of cardiac events in 1,530 patients from the Rochester-based LQTS Registry.
Results:
Relative to being off beta-blockers, the hazard ratios and 95% confidence intervals (CIs) for first cardiac events for atenolol, metoprolol, propranolol, and nadolol were: 0.71 (0.50-1.01), 0.70 (0.43-1.15), 0.65 (0.46-0.90), and 0.51 (0.35-0.74), respectively. In LQT1, the risk reduction for first cardiac event was similar among the four beta-blockers, but in LQT2, nadolol provided the only significant risk-reduction (hazard ratio, 0.40 [0.16-0.98]). Among patients who had a prior cardiac event while on beta-blockers, efficacy for recurrent events differed by drug, and propranolol was the least effective compared to the other beta-blockers.
Conclusions:
Although the four beta-blockers are equally effective in reducing the risk of a first cardiac event in LQTS, their efficacy differed by genotype, with nadolol being the only beta-blocker associated with a significant risk reduction in LQT2 patients. Patients experiencing cardiac events while on beta-blocker therapy are at high risk for subsequent cardiac events, and propranolol is the least effective drug in this high-risk group.
Perspective:
The use of beta-blockers in LQTS has been first-line standard therapy. In another recent study of previously asymptomatic LQTS patients, there was no difference in cardiac event occurrence between metoprolol, propranolol, and nadolol. Until further data are available, nadolol should be considered a first-line drug for LQT2, and propranolol should probably be avoided in all LQTS. Prospective randomized studies are needed to definitively answer the question of relative efficacy of the different beta-blockers.
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