Low-dose Landiolol Research Articles

Landiolol: An Ultra-Short-Acting β-Blocker.

Landiolol is an ultra-short-acting, highly cardio-selective, β-blocker, that is currently approved for clinical use in Japan and the European Union, for the treatment of tachyarrhythmias. Landiolol is highly cardio-selective with high β1 selectivity and receptor affinity, resulting in a more potent chronotropic effect and less potent hypotensive effect compared with other β-blockers such as esmolol and propranolol. Based on the recent randomized controlled trials, low-dose landiolol may have a beneficial role in the prevention and management of postoperative atrial fibrillation following noncardiac and cardiac surgeries, including on-pump and off-pump coronary artery bypass grafting and valve surgery. Additionally, landiolol may have potential utility for myocardial salvage and prevention of postpercutaneous coronary intervention myocardial infarction. Furthermore, the use of landiolol may also have a therapeutic effect for rate control of sepsis-related tachyarrhythmias. Positive results of recent randomized controlled trials should continue to inspire clinicians to conduct further, larger studies, to find new potential clinical applications for this novel drug.

Preventive effect of low-dose landiolol on postoperative atrial fibrillation study (PELTA study)

ObjectiveTo investigate the efficacy of prophylactic administration of low-dose landiolol on postoperative atrial fibrillation (POAF) in patients after cardiovascular surgery.MethodsConsecutive 150 patients over 70 years of age who underwent cardiovascular surgery for valvular, ischemic heart, and aortic diseases were enrolled in this single-center prospective randomized control study from 2010 to 2014. They were assigned to three treatment groups: 1γ group (landiolol at 1 μg/kg/min), 2γ group (landiolol at 2 μg/kg/min), or control group (no landiolol). In the two landiolol groups, landiolol hydrochloride was intravenously administered for a period of 4 days postoperatively. Electrocardiography was continuously monitored during the study period, and cardiologists eventually assessed whether POAF occurred or not.ResultsPOAF occurred in 24.4% of patients in the control group, 18.2% in 1γ group, and 11.1% in 2γ group (p = 0.256). Multivariate logistic regression analysis showed that the incidence of POAF tended to decrease depending on the dose of landiolol (trend-p = 0.120; 1γ group: OR = 0.786, 95% CI 0.257–2.404; 2γ group: OR = 0.379, 95% CI 0.112–1.287). Subgroup analysis showed a significant dose-dependent reduction in POAF among categories of female sex, non-use of angiotensin II receptor blockers (ARBs) before surgery, and valve surgery (each trend-p = 0.02, 0.03, and 0.004).ConclusionsThese findings indicate that prophylactic administration of low-dose landiolol may not be effective for preventing the occurrence of POAF in overall patients after cardiovascular surgery, but the administration could be beneficial to female patients, patients not using ARBs preoperatively, and those after valvular surgery.

Evaluating the Therapeutic Efficacy and Safety of Landiolol Hydrochloride for Management of Arrhythmia in Critical Settings: Review of the Literature.

BackgroundLandiolol hydrochloride, a highly cardio-selective beta-1 blocker with an ultra-short-acting half-life of 4 minutes, was originally approved by Japan for treatment of intraoperative tachyarrhythmias. This review aims to provide an integrated overview of the current state of knowledge of landiolol hydrochloride in the management of arrhythmia in critical settings.MethodsWe searched MEDLINE, EMBASE, and the Cochrane Library to retrieve relevant articles with a total of 65 records identified.ResultsThe high β1 selectivity (β1/β2 ratio of 255:1) of landiolol causes a more rapid heart rate (HR) decrease compared to esmolol while avoiding decreases in mean arterial blood pressure. Recently, it has been found useful in left ventricular dysfunction patients and fatal arrhythmia requiring emergency treatment. Recent random clinical trials (RCT) have revealed therapeutic and prophylactic effects on arrhythmia, and very low-dose landiolol might be effective for preventing postoperative atrial fibrillation (POAF) and sinus tachycardia. Likewise, landiolol is an optimal choice for perioperative tachycardia treatment during cardiac surgery. The high β1 selectivity of landiolol is useful in heart failure patients as a first-line therapy for tachycardia and arrhythmia as it avoids the typical depression of cardiac function seen in other β-blockers. Application in cardiac injury after percutaneous coronary intervention (PCI), protection for vital organs (lung, kidney, etc.) during sepsis, and stabilizing hemodynamics in pediatric patients are becoming the new frontier of landiolol use.ConclusionLandiolol is useful as a first-line therapy for the prevention of POAF after cardiac/non-cardiac surgery, fatal arrhythmias in heart failure patients and during PCI. Moreover, the potential therapeutic effect of landiolol for sepsis in pediatric patients is currently being explored. As positive RCT results continue to be published, new clinical uses and further clinical studies in various settings by cardiologists, intensivists and pediatric cardiologists are being conducted.

P4605Landiolol, a beta-blocker, optimizes cardiac energetics and peripheral microhemodynamics better than ivabradine while reducing heart rate at hemodynamic resuscitation of experimental septic shock

Abstract Background Septic shock is associated with sympathetic over-activation characterized by tachycardia, which is associated with poor survival. Though several kinds of drugs are available to reduce heart rate (HR), it is not clear which drug should be used to reduce HR effectively in initial hemodynamic resuscitation in septic shock. Purpose The aim of this study was to experimentally investigate comparative effects of landiolol (a β-blocker) and ivabradine (an If-channel inhibitor) on initial hemodynamic resuscitation in a canine model of endotoxin shock. Methods We used 19 anesthetized dogs. Seven dogs were allocated to control (CT) group, six dogs to landiolol (BB) group, and six dogs to ivabradine (IVA) group. In all the groups, endotoxin shock was induced by intravenous infusion of Escherichia coli lipopolysaccharide (4 mg/kg) over 1 h. After induction of endotoxin shock, we started hemodynamic resuscitation to restore mean arterial pressure (AP) and cardiac output (CO) by infusing noradrenaline (NA) and Ringer acetate solution (RiA). Dose of NA and RiA were automatically titrated with use of a computer-controlled drug infusion system that we developed previously. Hemodynamic resuscitation was continued for 4 h. During resuscitation, the BB group was given landiolol infusion at a low-dose range (1–10 μg/kg/min, manually titrated), while the IVA group was given ivabradine at 0.25 mg/kg bolus-injected every 2 h. Results The drug infusion system automatically restored AP to 70 mmHg and CO to greater than 90% of baseline level in all the groups. The restored AP and CO were not significantly different among the three groups (Figure A, B). There were no significant differences in the computer-controlled infusion rate of NA and cumulated volume of RiA infused among the three groups (Figure C). During the first 2 h of resuscitation, HR was significantly reduced in the BB and IVA groups in comparison to the CT group (Figure D). However, only in the BB group, cardiac oxygen consumption was significantly lower than that in the CT group (Figure E). Blood lactate level decreased significantly after hemodynamic resuscitation only within the BB group (Figure F). Figure 1 Conclusions In the initial hemodynamic resuscitation of septic shock, both low-dose landiolol infusion and ivabradine injection may be used to reduce HR. However, to optimize cardiac energetics and peripheral microhemodynamics, low-dose landiolol infusion may be preferable to ivabradine injection. Acknowledgement/Funding This work was supported by JSPS KAKENHI Grant Number 15K01307, 18K12126.

Low-Dose Landiolol Reduces Heart Rate and Cardiac Oxygen Consumption Without Compromising Initial Hemodynamic Resuscitation in a Canine Model of Endotoxin Shock.

In septic shock, it is not known whether β-blocker can be used to reduce heart rate (HR) safely during the initial phase of hemodynamic resuscitation. The purpose of this study was to experimentally investigate the effects of low-dose landiolol, a β-blocker, on initial hemodynamic resuscitation in dogs with endotoxin shock. In 13 anesthetized dogs [n = 7 in control (CT) group, n = 6 in β-blockade (BB) group], after endotoxin shock was induced by intravenous infusion of lipopolysaccharide (4 mg kg), we started hemodynamic resuscitation to restore mean arterial pressure (AP) and cardiac output (CO) by infusing noradrenaline (NA) and Ringer acetate solution (RiA). During 4 h of hemodynamic resuscitation, dose of NA and RiA were automatically titrated with use of a computer-controlled drug infusion system that we developed previously. In BB group, landiolol was administered at a low-dose range (1-10 μg kg min) to lower HR to lower than 140 bpm. Hemodynamic resuscitation using the system restored AP to 70 mmHg and CO to greater than 90% of baseline level similarly in both groups. Throughout resuscitation, HR and indices of cardiac contractility were significantly lower in BB group than in CT group. However, there were no significant intergroup differences in the dose of NA and RiA. During First 2 h of resuscitation, cardiac oxygen consumption was significantly lower in BB group than in CT group. In conclusion, low-dose landiolol may reduce HR without compromising initial hemodynamic resuscitation in septic shock. To clearly establish this, large-size randomized study using animal models more relevant to septic shock is needed.

Prevention of atrial fibrillation after cardiac surgery using low-dose landiolol: A systematic review and meta-analysis

Study objectiveAtrial fibrillation (AF) is associated with mortality after cardiac surgery. Several studies have reported that landiolol might help to prevent postoperative AF. The objective of this study was to investigate whether low-dose landiolol is useful in terms of balance of benefit and risk. DesignWe conducted a meta-analysis after systematically searching the PubMed, the Cochrane library and the ICHUSHI to identify randomized, controlled trials investigating the preventive effect of landiolol on incidence of AF after cardiac surgery. PatientsSix randomized trial with 571 patients were included. MeasurementsThe primary outcome was incidence of AF after surgery, while secondary outcomes were mortality and complications. Main resultsIncidence of AF within 1week after surgery was significantly lower in the landiolol group than in the control group (odds ratio, 0.27; 95% confidence interval, 0.18–0.42; p<0.001). Three of the 6 studies reported data regarding in-hospital mortality and complications, showing no significant differences between groups (0.7 vs 3.0%; OR, 0.45; 95% CI, 0.07–2.74; p=0.39; and 4.5 vs 9.7%; OR, 0.45; 95% CI, 0.16–1.23; p=0.12, respectively). ConclusionsOur systematic review revealed that low-dose landiolol might help to prevent AF after cardiac surgery and further large trials are needed to evaluate safety because mortality and morbidity rate were very low in included studies.

A randomized, open label study of the efficacy of prophylactic 24-h low-dose landiolol for atrial fibrillation in transthoracic esophagectomy

Atrial fibrillation (Af) is one of the common cardiovascular complications after esophagectomy. Low-dose landiolol prevented postoperative Af after administration was previously reported. We evaluated the preventive effects and safety of landiolol, a β1-selective blocker, on postoperative tachycardia (≥120 bpm) or Af after esophagectomy. Eighty consecutive patients scheduled for esophagectomy at our institute between July 2009 and March 2014. Patients were randomly assigned to a landiolol or control group. Landiolol was administrated at 5 μg/kg/min for 24 h after induction of anesthesia. Electrocardiography was monitored continuously for 2 days after surgery. There were no significant differences in patient background between the control group (n = 40) and the landiolol group (n = 39) except for one patient with preoperative Af. Af was identified in only one patient in the control group, and the onset was on the second postoperative day. Overall, the incidence of Af was 1.3 % (1/79). Incidences of tachycardia were 12.5 and 12.8 % in the control group and the landiolol group, respectively. No adverse event was identified. This study could not show the superiority of prophylactic 24-h low-dose landiolol for postoperative Af in transthoracic esophagectomy. High-risk patients might be candidates for preventive landiolol.

Perioperative Landiolol Infusion Reduces the Incidence of Atrial Fibrillation after Pulmonary Lobectomy: Postoperative Randomized Controlled Study

Background and Objective: Atrial fibrillation is a common complication after lung resection. We sought to determine the relationship between low-dose landiolol only intraoperatively administration and the incidence of atrial fibrillation development in patients who did not have atrial fibrillation before undergoing lung resection. Methods: Forty-five patients undergoing lung resection (lobectomy or bilobectomy), as indicated for lung cancer at Nippon Medical Hospital, between August 2012 and September 2013. Two patients were excluded from the final analysis. Patients were given either intravenous landiolol (n = 22) or placebo (n = 21) during lobectomy or bilobectomy only intraoperatively. This is prospective, randomized, placebo-controlled study. Main Outcome Measures: The primary end point was the incidence of sustained atrial fibrillation (≥30 min). Results: Postoperative atrial fibrillation occurred in 1 (4.5%) of the 22 patients in the landiolol group and 6 (28.6%) of the 21 patients in the placebo group. No serious adverse effects such as bradycardia and hypotention secondary to landiolol were observed. Conclusion: Low-dose landiolol infusion intraoperatively reduced the incidence of clinically significant atrial fibrillation in patients undergoing pulmonary lobectomy.

Abstract 13382: Urgent Control of Rapid Atrial Tachyarrhythmia Using Landiolol in Patients With Heart Failure With Severely Reduced Ejection Fraction : An Ultra-Short-Acting β-blocker for Emergency ADHF

Backgounds: To control heart rate(HR) of atrial tachyarrhythmia is important in patients with acute decompensated heart failure(ADHF) in their critical phase. Landiolol is newly developed an ultra-short-acting β-blocker. We explored the hemodynamic effect of Landiolol treatment for atrial tachyarrhythmia in patients with ADHF in their critical phase. Hypothesis: Landiolol is useful to control HR of atrial tachyarrhythmia without any adverse events and it can make their status better. Methods: Consecutive 35 ADHF patients were enrolled(74 years, 25 men, EF25%, HR137/min, BNP837pg/ml). 34 out of 35 patients had atrial fibrillation (AF) or atrial flutter (AFL), and one patient had atrial tachcardia (AT). We treated them with low dose landiolol immediately after admission. Among them, 17 patients were monitored by Swan-Ganz (S-G) catheterization to explore the hemodynamic effect of Landiolol. Results: The average maximum dose of Landiolol was 3.3γ. No patients had serious adverse events. HR (93/min, p&lt;0.0001) and BNP (618pg/ml, p&lt;0.05 ) decreased after treatment and In S-G data, PCWP and PAP decreased after Landiolol treatment, on the other hand CO increased. Three patients out of 17 patients with S-G could not achieve adequate HR decrease (110&lt;min) even with their maximum dose, their ΔHR were -28, -28, +1/min.. They had higher PCWP (32 vs 20, p&lt;0.05) and relatively lower CO (2.7 vs 3.0, NS) compared with responders. One patient had AT and his HR didn’t decrease (ΔHR= +1/min) and hemodynamic condition didn't improve. Conclusions: Low dose Landiolol that is an ultra-short-acting β-blocker, was effective for controlling rapid HR in AF/AFL patients with LV dysfunction despite being in the critical state. The patients with extremely severe condition and atrial tachycardia might not be suitable for Landiolol treatment in their critical states.

Prevention of immediate recurrence of atrial fibrillation with low-dose landiolol after radiofrequency catheter ablation

BackgroundImmediate recurrence of atrial fibrillation (AF) after radiofrequency (RF) catheter ablation is commonly observed within 3d after the procedure. The mechanism and pharmacological management of immediate AF recurrence remain unclear. MethodsA total of 50 consecutive patients with paroxysmal AF were randomized to receive either low-dose landiolol (landiolol group) or a placebo (placebo group). In the landiolol group, intravenous landiolol (0.5μgkg−1min−1) was administered for 3d after AF ablation. ResultsNo serious adverse event associated with RF catheter ablation or landiolol administration was observed. The prevalence of immediate AF recurrence (≤3d after RF catheter ablation) was significantly lower in the landiolol group than in the placebo group (16% vs. 48%, p=0.015). Although the postprocedural change in heart rate was significantly lower in the landiolol group compared to that in the placebo group, the changes in blood pressure and body temperature were not different between the two groups. Multiple logistic regression analysis revealed that landiolol treatment was the only independent predictor of immediate AF recurrence after ablation (odds ratio: 0.180; 95% confidence interval: 0.044–0.729; p=0.016). ConclusionsProphylactic administration of low-dose landiolol after AF ablation may be effective and safe for preventing immediate AF recurrence within 3d after AF ablation.

A low-dose β1-blocker in combination with milrinone improves intracellular Ca2+ handling in failing cardiomyocytes by inhibition of milrinone-induced diastolic Ca2+ leakage from the sarcoplasmic reticulum.

ObjectivesThe purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism.BackgroundThe molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca2+ handling in heart failure remains unclear.MethodsWe investigated the effect of milrinone plus landiolol on intracellular Ca2+ transient (CaT), cell shortening (CS), the frequency of diastolic Ca2+ sparks (CaSF), and sarcoplasmic reticulum Ca2+ concentration ({Ca2+}SR) in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2) and phospholamban (PLB).ResultsIn failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca2+}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca2+}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808) in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17). Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz) in failing cardiomyocytes.ConclusionA low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca2+ leak.

Preventive effect of intraoperative landiolol administration on atrial fibrillation after off-pump coronary artery bypass grafting.

IntroductionPostoperative atrial fibrillation (AF) is a common complication of cardiac surgery that is associated with an increased incidence of other complications. This study evaluated the safety and efficacy of landiolol hydrochloride—an ultrashort-acting β1-selective blocker and highly regulated drug, positioned as a class 1 antiarrhythmic in Japan guidelines—for the prevention of AF after off-pump coronary artery bypass grafting (CABG).MethodsBetween January 2011 and November 2013, 116 patients underwent CABG at Fukuoka University Hospital. They were divided into two groups: group L consisted of patients who were administered landiolol hydrochloride at 2 μg/kg/min after completion of all distal anastomoses; group C was the control group consisting of patients who were not administered landiolol. Patient backgrounds, intraoperative variables and incidence of postoperative complications were compared.ResultsNo significant between-group differences were observed in patient backgrounds or incidence of complications other than postoperative AF, which occurred significantly less frequently in group L. After administration of landiolol, heart rate decreased but no change was observed in arterial pressure or other parameters, and patient hemodynamics remained stable.ConclusionIntraoperative and perioperative administration of low-dose landiolol has a preventive effect on the development of AF after CABG surgery.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-014-0158-0) contains supplementary material, which is available to authorized users.

A comparison of bolus injection of landiolol versus oral administration of propranolol before cardiac computed tomography

Heart rate (HR) reduction is essential to achieve good image quality for cardiac computed tomography (CCT). We evaluated the efficacy of a bolus injection of landiolol, an ultra-short acting β-blocker, without the administration of oral β-blocker to reduce HR prior to CCT. We enrolled 678 consecutive patients who underwent CCT from December 2011 to March 2012 and divided them into three groups, which were a propranolol group (n = 277), a low-dose landiolol group (n = 188), and a high-dose landiolol group (n = 213). Patients in the propranolol group received oral propranolol (10–20 mg) prior to CCT. Patients in the low-dose and high-dose landiolol groups were administered a bolus injection of landiolol (0.125 mg/kg), while the high-dose group received an additional 3.75 mg of landiolol if the baseline HR was ≥75/min. Although the average HR was significantly lower in the propranolol group (61.6 ± 8.0/min) than in the low-dose landiolol group (64.1 ± 7.4/min, P < 0.001), there was no significant difference in the image quality (P = 0.91). Among patients with baseline HR ≥75/min, the average HR tended to be lower in the high-dose landiolol group (67.2 ± 6.9/min) compared with the low-dose landiolol group (69.0 ± 6.9/min, P = 0.10), and there was a corresponding difference in image quality between these two groups (P = 0.02). In conclusion, Although the decrease of HR was significantly larger in the propranolol group than in the landiolol groups, the image quality was similar. Among the patients who received landiolol, a higher dose was associated with a lower HR and better image quality. Further investigation to assess higher-dose bolus injection of landiolol or bolus injection following oral administration of a β-blocker would be needed.

A Low-Dose β1-Blocker Effectively and Safely Slows the Heart Rate in Patients with Acute Decompensated Heart Failure and Rapid Atrial Fibrillation

Objective: Recently, we reported that low-dose landiolol (1.5 µg·kg^-1·min^-1), an ultra-short-acting β-blocker, safely decreased the heart rate (HR) in patients with acute decompensated heart failure (ADHF) and sinus tachycardia, thereby improving cardiac function. We investigated whether low-dose landiolol effectively decreased the HR in ADHF patients with rapid atrial fibrillation (AF). Methods: We enrolled 23 ADHF patients with rapid AF (HR ≥120 beats·min^-1 and New York Heart Association class III-IV) and systolic heart failure (SHF: n = 12) or diastolic heart failure (DHF: n = 11) who received conventional therapy with diuretics, vasodilators, and/or low-dose inotropes. They were administered continuous intravenous infusion of low-dose landiolol (1.0-2.0 µg·kg^-1·min^-1), and their electrocardiograms and blood pressures were monitored for 24 h thereafter. Results: Two hours after starting landiolol, the HR was reduced significantly (22%), without a reduction in blood pressure, and remained constant thereafter. The HR reduction 2 h after landiolol administration was significantly greater in the DHF group than in the SHF group. No incidence of hypotension was recorded. Conclusions: Digitalis or amiodarone is currently recommended for HR control in ADHF patients with rapid AF. Our results showed that continuous infusion of low-dose landiolol may also be useful as first-line therapy in these patients.

Landiolol for junctional ectopic tachycardia refractory to amiodarone after pediatric cardiac surgery

Postoperative junctional ectopic tachycardia (JET) in children undergoing cardiac surgery is a serious arrhythmia that is associated with considerable morbidity and mortality. We present here a case of successful landiolol therapy for postoperative JET in a 3-month-old infant who underwent ventricular septal defect closure and right pulmonary artery plasty. His left ventricular function was poor postoperatively. The JET was refractory to amiodarone and caused severe hypotension, which was required cardiac massage. Continuous intravenous infusion of low-dose landiolol reduced the persistent JET rate immediately, and restored to sinus rhythm with stable hemodynamics.

Low-Dose β-Blocker in Combination With Milrinone Safely Improves Cardiac Function and Eliminates Pulsus Alternans in Patients With Acute Decompensated Heart Failure

The purpose of this study was to determine whether a low-dose β-blocker, in combination with milrinone, improves cardiac function in acute decompensated heart failure (ADHF) with tachycardia. Twenty ADHF patients (New York Heart Association classification III, n=1, and IV, n=19; heart rate [HR], 107±12 beats/min; left ventricular ejection fraction, 24±7%; cardiac index [CI], 2.2±0.6 L·min(-1)·m(-2); pulmonary capillary wedge pressure [PCWP], 26±8 mmHg) were enrolled in this study. The patients first underwent conventional therapy with milrinone, vasodilators and diuretics; landiolol (1.5-6.0 µg·kg(-1)·min(-1); i.v.), which is an ultra-short-acting β(1)-selective blocker, was then added to the treatment regimen to study its effect on hemodynamics. Low-dose landiolol (1.5 µg·kg(-1)·min(-1)) significantly reduced HR by 11% without changing blood pressure (BP) and CI, whereas higher doses (≥3.0 µg·kg(-1)·min(-1)) tended to decrease BP and CI while increasing PCWP and systemic vascular resistance. After treatment with landiolol (1.5 µg·kg(-1)·min(-1)), hemodynamic parameters such as PCWP, stroke volume index, SvO(2), rate pressure product, filling time/RR, E/e', and Tei index were significantly improved. A low-dose β-blocker in combination with milrinone improved cardiac function in ADHF patients with tachycardia; therefore, it may be considered as an adjunct therapy for use when standard therapy with milrinone is not effective at slowing HR.

Efficacy of low-dose landiolol, an ultrashort-acting β-blocker, on postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer

Postoperative atrial fibrillation is the most common complication encountered during the early postoperative period following a pulmonary resection procedure. Landiolol is a newly developed, ultrashortacting, β-adrenoceptor antagonist. The objective of the present study was to evaluate the efficacy and safety of low-dose landiolol for postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer. Of 553 patients who underwent an elective pulmonary resection procedure for lung cancer at National Toneyama Hospital from January 2005 to December 2009, this analysis involved 30 consecutive patients who developed atrial fibrillation after surgery and needed treatment. These patients were divided into two groups: the landiolol group (n = 15) and the historical control group (treated with a combination of verapamil and digoxin, n = 15). Hemodynamic changes before and 30 min, 2 h, and 12 h after medication, the time required to restore sinus rhythm, and adverse events were evaluated. There were no significant differences between the two groups regarding blood pressure before and after medication. Heart rate was reduced immediately in both groups after medication and was significantly lower in the landiolol group than in the control group. The time to restore sinus rhythm was significantly shorter in the landiolol group than in the control group (8.1 ± 11.0 h vs. 23.0 ± 26.0 h, P < 0.05). In none of the subjects with the landiolol infusion was it discontinued because of side effects. Low-dose landiolol can be effective quickly and used safely in patients who develop atrial fibrillation after pulmonary resection for lung cancer.

Postoperative Treatment of Carvedilol Following Low Dose Landiolol has Preventive Effect for Atrial Fibrillation after Coronary Artery Bypass Grafting

Postoperative atrial fibrillation (AF) is the most common complication after coronary artery bypass grafting (CABG). We have reported that the intra- and perioperative administration of landiolol has a preventive effect on postoperative AF in the early postoperative period after CABG surgery. The purpose of this study was to investigate the prophylactic effect of postoperative treatment with carvedilol following landiolol against postoperative AF. We reviewed all patients who underwent CABG from December 2005 and February 2009. Fifty-three patients underwent scheduled isolated CABG and were divided two groups; carvedilol group (n = 31), and control group (n = 22). Incidences of postoperative AF were noted. There was no statistical difference between the two groups with regard to the occurrence of AF after CABG. The maximum ventricular rate of AF was significantly lower in the carvedilol group than in the control group. All patients with AF in the control group needed treatment for tachycardia, but this was not necessary in the carvedilol group. Postoperative treatment with carvedilol following landiolol has the effect of preventing tachycardia during AF after coronary artery bypass grafting.

Effect of low-dose landiolol, an ultrashort-acting β-blocker, on postoperative atrial fibrillation after CABG surgery

Postoperative atrial fibrillation is the most common complication after coronary artery bypass grafting (CABG). This complication is associated with prolongation of the intensive care unit stay and hospitalization time with attendant increased hospitalization costs, and it is an important risk factor for perioperative cerebrovascular accidents. Landiolol is a newly developed ultrashort-acting beta-adrenoceptor antagonist with a half-life of 3 min that is eight times more cardioselective than esmolol. The purpose of this study was to investigate the prophylactic effect of continuous administration of low-dose landiolol on postoperative atrial fibrillation. We reviewed all patients who underwent CABG alone at our hospital from April 2002 and September 2006. Patients with a previous history of atrial arrhythmias were excluded. The remaining patients were divided to two groups: landiolol group (n = 20), and control group (n = 35). Administration of landiolol started after cardiopulmonary bypass with a loading dose of 1.5-2.5 mug.kg(t-1).min(-1) and continued for the first 2 days after surgery. The incidence of postoperative atrial fibrillation was noted. Continuous variables were compared between groups by means of Student's t-test. Categorical variables were compared by means of the chi(2) test or Fisher's exact test. The occurrence of atrial fibrillation after CABG in the control group was statistically more than in the landiolol group (P = 0.04). There were no statistical differences between the groups regarding the cardiac index or the dose of inotropic agents during the perioperative period. Intraoperative and perioperative administration of low-dose landiolol has a preventive effect on the appearance of atrial fibrillation after CABG surgery.

Low-dose landiolol for hypertension with tachycardia following neurosurgery

Low-dose landiolol for hypertension with tachycardia following neurosurgery