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Background In LQTS, β-blocker therapy is effective in reducing the risk of cardiac events (syncope, aborted cardiac arrest, sudden cardiac death). Limited studies have compared the efficacy of different β-blockers. Objectives The goal of this study was to compare the efficacy of different β-blockers in long QT syndrome (LQTS) and in genotype-positive patients with LQT1 and LQT2. Methods The study included 1,530 patients from the Rochester, New York–based LQTS Registry who were prescribed common β-blockers (atenolol, metoprolol, propranolol, or nadolol). Time-dependent Cox regression analyses were used to compare the efficacy of different β-blockers with the risk of cardiac events in LQTS. Results Relative to being off β-blockers, the hazard ratios and 95% confidence intervals (CIs) for first cardiac events for atenolol, metoprolol, propranolol, and nadolol were 0.71 (0.50 to 1.01), 0.70 (0.43 to 1.15) 0.65 (0.46 to 0.90), and 0.51 (0.35 to 0.74), respectively. In LQT1, the risk reduction for first cardiac events was similar among the 4 β-blockers, but in LQT2, nadolol provided the only significant risk reduction (hazard ratio: 0.40 [0.16 to 0.98]). Among patients who had a prior cardiac event while taking β-blockers, efficacy for recurrent events differed by drug (p = 0.004), and propranolol was the least effective compared with the other β-blockers. Conclusions Although the 4 β-blockers are equally effective in reducing the risk of a first cardiac event in LQTS, their efficacy differed by genotype; nadolol was the only β-blocker associated with a significant risk reduction in patients with LQT2. Patients experiencing cardiac events during β-blocker therapy are at high risk for subsequent cardiac events, and propranolol is the least effective drug in this high-risk group.

Background In prior clinical studies of patients with long QT syndrome (LQTS), pregnancy was associated with fewer cardiac events (CEs) compared to before or after pregnancy. In recent animal studies involving rabbits with LQTS mutations, progesterone had favorable effects on CEs compared to estrogen. The effect of oral contraceptive therapy with its high progesterone/estrogen ratio on the risk of CEs in patients with LQTS has not been examined. Objective To study the effect of oral contraceptive use on the risk of CEs in patients with LQTS. Methods We studied 174 patients from the Rochester-based LQTS Registry who responded to a questionnaire about their oral contraceptive use. We used time-dependent Cox regression to estimate the hazard ratio for recurrent CEs when patients were using vs not using oral contraceptives during nonpregnancy periods. For this recurrent events analysis, the Prentice-Williams-Peterson model was used and the time origin was defined as the onset of menarche. We adjusted for the baseline corrected QT interval, history of CEs before menarche, age at menarche onset, number of births, time-dependent β-blocker therapy, and LQTS genotype. Results No differences in the risk of CEs for the times patients with LQTS were using vs not using oral contraceptives was found in the general population with LQTS (hazard ratio 1.01; P = .95) or in analyses of LQTS subsets (P > .2). Conclusion Oral contraceptive therapy use did not affect LQTS-related CEs in the study population. Oral contraceptives did not show beneficial or harmful effects in this patient group.

Objectives The goal of this study was to evaluate the effects of carvedilol and metoprolol on the endpoint of inappropriate implantable cardioverter-defibrillator therapy in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy) study. Background The impact of carvedilol and metoprolol on inappropriate therapy in heart failure patients with devices has not yet been investigated. Methods All patients in the MADIT-CRT study who received a device (N = 1,790) were identified. Using time-dependent Cox regression analysis, we compared patients treated with different types of beta-blockers or no beta-blockers on the primary endpoint of inappropriate therapy, delivered as antitachycardia pacing (ATP) or shock therapy. Secondary endpoints were inappropriate therapy due to atrial fibrillation and atrial tachyarrhythmias, also evaluated as ATP or shock therapy. Results Inappropriate therapy occurred in 253 (14%) of 1,790 patients during a follow-up period of 3.4 ± 1.1 years. Treatment with carvedilol was associated with a significantly decreased risk of inappropriate therapy compared with metoprolol (hazard ratio [HR]: 0.64 [95% confidence interval (CI): 0.48 to 0.85]; p = 0.002). The reduction in risk was consistent for inappropriate ATP (HR: 0.66 [95% CI: 0.48 to 0.90]; p = 0.009) and inappropriate shock therapy (HR: 0.54 [95% CI: 0.36 to 0.80]; p = 0.002). The risk of inappropriate therapy caused by atrial fibrillation was also reduced in patients receiving carvedilol compared with metoprolol (HR: 0.50 [95% CI: 0.32 to 0.81]; p = 0.004). General use of beta-blockers (93%) and adherence in this study was high. Conclusions In heart failure patients undergoing either cardiac resynchronization therapy with a defibrillator or with an implantable cardioverter-defibrillator device, carvedilol was associated with a 36% lower rate of inappropriate ATP and shock therapy compared with metoprolol. Inappropriate therapy due to atrial fibrillation was associated with a 50% lower rate in patients receiving carvedilol compared with those receiving metoprolol. (MADIT-CRT: Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy; NCT00180271 )

In prior clinical studies of patients with long QT syndrome (LQTS), pregnancy was associated with fewer cardiac events (CEs) compared to before or after pregnancy. In recent animal studies involving rabbits with LQTS mutations, progesterone had favorable effects on CEs compared to estrogen. The effect of oral contraceptive therapy with its high progesterone/estrogen ratio on the risk of CEs in patients with LQTS has not been examined.To study the effect of oral contraceptive use on the risk of CEs in patients with LQTS.We studied 174 patients from the Rochester-based LQTS Registry who responded to a questionnaire about their oral contraceptive use. We used time-dependent Cox regression to estimate the hazard ratio for recurrent CEs when patients were using vs not using oral contraceptives during nonpregnancy periods. For this recurrent events analysis, the Prentice-Williams-Peterson model was used and the time origin was defined as the onset of menarche. We adjusted for the baseline corrected QT interval, history of CEs before menarche, age at menarche onset, number of births, time-dependent β-blocker therapy, and LQTS genotype.No differences in the risk of CEs for the times patients with LQTS were using vs not using oral contraceptives was found in the general population with LQTS (hazard ratio 1.01; P = .95) or in analyses of LQTS subsets (P.2).Oral contraceptive therapy use did not affect LQTS-related CEs in the study population. Oral contraceptives did not show beneficial or harmful effects in this patient group.

ObjectivesThe goal of this study was to evaluate the effects of carvedilol and metoprolol on the endpoint of inappropriate implantable cardioverter-defibrillator therapy in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy) study.BackgroundThe impact of carvedilol and metoprolol on inappropriate therapy in heart failure patients with devices has not yet been investigated.MethodsAll patients in the MADIT-CRT study who received a device (N = 1,790) were identified. Using time-dependent Cox regression analysis, we compared patients treated with different types of beta-blockers or no beta-blockers on the primary endpoint of inappropriate therapy, delivered as antitachycardia pacing (ATP) or shock therapy. Secondary endpoints were inappropriate therapy due to atrial fibrillation and atrial tachyarrhythmias, also evaluated as ATP or shock therapy.ResultsInappropriate therapy occurred in 253 (14%) of 1,790 patients during a follow-up period of 3.4 ± 1.1 years. Treatment with carvedilol was associated with a significantly decreased risk of inappropriate therapy compared with metoprolol (hazard ratio [HR]: 0.64 [95% confidence interval (CI): 0.48 to 0.85]; p = 0.002). The reduction in risk was consistent for inappropriate ATP (HR: 0.66 [95% CI: 0.48 to 0.90]; p = 0.009) and inappropriate shock therapy (HR: 0.54 [95% CI: 0.36 to 0.80]; p = 0.002). The risk of inappropriate therapy caused by atrial fibrillation was also reduced in patients receiving carvedilol compared with metoprolol (HR: 0.50 [95% CI: 0.32 to 0.81]; p = 0.004). General use of beta-blockers (93%) and adherence in this study was high.ConclusionsIn heart failure patients undergoing either cardiac resynchronization therapy with a defibrillator or with an implantable cardioverter-defibrillator device, carvedilol was associated with a 36% lower rate of inappropriate ATP and shock therapy compared with metoprolol. Inappropriate therapy due to atrial fibrillation was associated with a 50% lower rate in patients receiving carvedilol compared with those receiving metoprolol. (MADIT-CRT: Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy; NCT00180271)

The effect of different beta-blockers on inappropriate therapy in heart failure patients with devices has not been investigated previously. All patients in the MADIT-CRT study who received a device (N=1790) were identified and treatment or no treatment with different types of beta-blockers were