Assessment of a novel transdermal selective ß1-blocker, the bisoprolol patch, for treating frequent premature ventricular contractions in patients without structural heart disease.

BACKGROUND: The autonomic nervous system involves the genesis of premature ventricular contractions (PVCs). Previous studies demonstrated that heart rate (HR) dependency of idiopathic PVCs has different autonomic mechanisms. Recently, the bisoprolol patch, a novel transdermal ß1-blocker formulation containing bisoprolol, became clinically available. We examined the efficacy of the bisoprolol patch for treating frequent PVCs in patients without structural heart disease (SHD) regarding the HR dependency of PVCs. METHODS: This prospective study included 44 consecutive patients without SHD (25 men, mean age, 63.6±12.3 years) with PVC counts≥3000 beats as measured by 24-hour Holter electrocardiograms (ECGs). PVCs were divided into positive HR-dependent PVCs (P-PVCs) and non-positive HR-dependent PVCs (NP-PVCs) based on the relationship between the hourly PVC density and hourly mean HR. A bisoprolol patch was administered once daily at a dose of 4mg. The 24-hour Holter ECGs were performed before and 1 month after the initiation of the therapy. RESULTS: In 44 patients, there were 24 P-PVCs and 20 NP-PVCs. The bisoprolol patch reduced the PVC count significantly (from 16,563±10,056 to 7892±8817 beats/24hours, p<0.001) in the P-PVC group, while the PVC count did not change significantly (from 16,409±9571 to 13,476±12,191beats/24hours, p=0.34) in the NP-PVC group. Moreover, in the P-PVC group, the patients with mean HRs ≥80 beats/minute had a significantly higher percent improvement in the PVC count than those with mean HRs <80 beats/minute (p=0.0080). The bisoprolol patch resulted in a significant reduction in the PVC count from baseline during each time period for the changes within a 24-hour period in the P-PVC group. CONCLUSIONS: The transdermal bisoprolol patch was effective for a PVC reduction in patients with P-PVCs, particularly in those with faster mean HRs. Furthermore, it demonstrated a stable PVC-reducing effect during the 24-hour period in the P-PVC group.

Assessment of drug-induced proarrhythmias due to pilsicainide in patients with atrial tachyarrhythmias.

BACKGROUND: Pilsicainide, a pure Na+ channel blocker, is a popular antiarrhythmic drug for the management of atrial tachyarrhythmias (AT), in Japan. However, serious drug-induced proarrhythmias (DIPs) may unexpectedly occur. We assessed the clinical background of AT patients presenting with DIPs caused by pilsicainide. METHODS: This study retrospectively enrolled 874 consecutive patients (543 men, 63.6±15.3 years old, and 57.9±16.5 kg of body weight), who were orally administered pilsicainide for AT management. We evaluated the relationship between DIPs and serum pilsicainide concentration, renal dysfunction (estimate glomerular filtration rate, eGFR), and electrocardiogram (ECG) parameters. RESULTS: Among the patients, 154 (17.6%) had renal dysfunction (eGFR<50 mL/min), including 12 (1.4%) on hemodialysis. DIPs were present in 10 patients (1.1%): all had renal dysfunction, and one was on hemodialysis. The eGFR in DIP patients was significantly lower than that in the non-DIP patients (32.2±15.1 vs. 68.4±22.1 mL/min, p<0.001). Among the clinical factors measured, only renal dysfunction (eGFR<50 mL/min) was significantly associated with DIPs (OR 44.6; 95% CI 5.61-335.0, p<0.001). Interestingly, among the ECG parameters, the corrected QT (QTc) intervals in DIP patients were longer than those in non-DIP patients (555.8±37.6 vs. 430.7±32.6 ms, p<0.001). As pilsicainide concentration increased, both QRS and QTc intervals prolonged. The latter were improved by discontinuing pilsicainide administration, and additional treatments. CONCLUSIONS: DIPs caused by pilsicainide administration were strongly associated with renal dysfunction. Hence, confirmation of renal function would be necessary prior to and/or during the pilsicainide administration.