Background: Landiolol, a highly cardioselective agent with a short half-life (2.4-4 min), is commonly used as a perfusor or bolus application to treat tachycardic arrhythmia. Some small studies suggest that prior oral β-blocker use results in a less effective response to intravenous β-blockers. Methods: This study investigated whether prior chronic oral β-blocker (Lβ) or no prior chronic oral β-blocker (L-) intake influences the response to intravenous push-dose Landiolol in intensive care patients with acute tachycardic arrhythmia. Results: The effects in 30 patients (67 [55-72] years) were analyzed, 10 (33.3%) with and 20 (66.7%) without prior oral β-blocker therapy. Arrhythmias were diagnosed as tachycardic atrial fibrillation in 14 patients and regular, non-fluid-dependent, supraventricular tachycardia in 16 cases. Successful heart rate control (Lβ 4 vs. L- 7, p = 1.00) and rhythm control (Lβ 3 vs. L- 6, p = 1.00) did not significantly differ between the two groups. Both groups showed a significant decrease in heart rate when comparing before and after the bolus administration, without significant differences between the two groups (Lβ -26/min vs. L- -33/min, p = 0.528). Oral β-blocker therapy also did not influence the change in mean arterial blood pressure after Landiolol bolus administration (Lβ -5 mmHg vs. L- -4 mmHg, p = 0.761). Conclusions: A prior chronic intake of β-blockers neither affected the effectiveness of push-dose Landiolol in heart rate or rhythm control nor impacted the difference in heart rate or mean arterial blood pressure before and after the Landiolol boli.

We investigated for the first time the suitability of landiolol, an ultra-short-acting β1-specific β-blocker, for the treatment of atrial fibrillation/atrial flutter (AF/AFL) in Caucasian patients.Methods and Results:The 20 study patients received landiolol as a continuous infusion (starting dose 40 µg/kg/min) with (B+CI) or without (CI) a preceding bolus dose (100 µg/kg/min administered over 1 min) in a prospective open-label study. The primary endpoint was the proportion of patients with sustained heart rate (HR) reduction ≥20% or to <90 beats/min within 16 min of starting the CI. Secondary endpoints were the pharmacodynamics, pharmacokinetics, AF/AFL symptoms, safety and tolerability of landiolol. At 16 min, HR was reduced in all patients treated with landiolol. The primary endpoint was met by 60% of patients in the CI group and 40% in the B+CI group without a significant group difference. Overall reduction of AF/AFL symptoms at 16 min was 72%. Safety and local tolerability of landiolol were excellent, and no serious adverse events occurred.
Continuous infusion of landiolol with a starting dose of 40 µg/kg/min is suitable for the acute treatment of tachycardic AF/AFL in Caucasian patients. Administration of a preceding bolus seems unnecessary.

A number of observational studies have reported that, in patients with chronic obstructive pulmonary disease (COPD), β blockers (BBs) decrease risk of mortality and COPD exacerbations. To address important methodological concerns of these studies, we compared the effectiveness and safety of cardioselective BBs versus non-dihydropyridine calcium channel blockers (non-DHP CCBs) in patients with COPD and acute coronary syndromes (ACS) using a propensity score (PS)-matched, active comparator, new user design. We also assessed for potential unmeasured confounding by examining a short-term COPD hospitalisation outcome.
We identified 22 985 patients with COPD and ACS starting cardioselective BBs or non-DHP CCBs across 5 claims databases from the USA, Italy and Taiwan.
Stratified Cox regression models were used to estimate HRs for mortality, cardiovascular (CV) hospitalisations and COPD hospitalisations in each database after variable-ratio PS matching. Results were combined with random-effects meta-analyses.
Cardioselective BBs were not associated with reduced risk of mortality (HR, 0.90; 95% CI 0.78 to 1.02) or CV hospitalisations (HR, 1.06; 95% CI 0.91 to 1.23), although statistical heterogeneity was observed across databases. In contrast, a consistent, inverse association for COPD hospitalisations was identified across databases (HR, 0.54; 95% CI 0.47 to 0.61), which persisted even within the first 30 days of follow-up (HR, 0.55; 95% CI 0.37 to 0.82). Results were similar across a variety of sensitivity analyses, including PS trimming, high dimensional-PS matching and restricting to high-risk patients.
This multinational study found a large inverse association between cardioselective BBs and short-term COPD hospitalisations. The persistence of this bias despite state-of-the-art pharmacoepidemiologic methods calls into question the ability of claims data to address confounding in studies of BBs in patients with COPD.

OBJECTIVE: Use of β-blockers (BBs) in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular diseases is supported by increasing evidence. However, most of these studies focused on the survival outcome and used a non-active comparison, prevalent-user design. We aimed to examine the risk of overall death and cardiovascular outcomes associated with use of cardioselective BBs using an active comparison, incident cohort approach.
METHODS: We identified COPD patients initiating cardioselective BBs or non-dihydropyridine calcium channel blockers (CCBs) between 2007 and 2011 in the population-based Taiwan database. A Cox regression model was applied to estimate hazard ratios (HRs) for overall death, cardiovascular death, and cardiovascular events comparing cardioselective BBs and non-dihydropyridine CCBs after propensity score matching. We also conducted sensitivity analyses to quantify the unmeasured confounding effect from COPD severity.
RESULTS: A total of 107,902 patients were included. Cardioselective BBs were associated with a modest, lower risk of overall death (HR, 0.85; 95 % CI, 0.81-0.88). The reduced risk of overall death, however, was vulnerable to distribution of COPD severity and was easily weakened with lower prevalence of severe COPD patients in the initiators of cardioselective BBs and higher prevalence of severe COPD patients in the initiators of non-dihydropyridine CCBs. No excess benefit for cardiovascular death (HR, 1.05; 95 % CI, 0.97-1.13) or cardiovascular events (HR, 0.98; 95 % CI, 0.94-1.03) was detected.
CONCLUSIONS: The present study demonstrated a potential effect of confounding by COPD severity and therefore did not suggest an association between use of cardioselective BB and survival benefit in COPD patients.