What is the available evidence in using Rapibylk (landiolol), a fast-acting IV beta blocker, indicated for postop afib patients?

Comment by InpharmD Researcher

Landiolol, an ultra-short-acting intravenous β1-selective beta blocker, appears effective for both prevention and management of atrial fibrillation in critically ill and surgical patients. Evidence suggests it reduces the incidence of postoperative atrial fibrillation, shortens hospital stay in some settings, and achieves rapid rate or rhythm control with minimal hemodynamic compromise. In critically ill patients with new-onset atrial fibrillation, landiolol demonstrated consistent conversion rates to sinus rhythm and a notable reduction in heart rate. Its favourable safety and efficacy profile supports its use in these populations. We would also like to acknowledge that we have received your request for a full monograph and our team is currently working on it. In the meantime, we’re providing this response to support your immediate needs.

Background

The efficacy and tolerability of landiolol, an ultra-short-acting intravenous β1-selective beta blocker, for the management of new-onset atrial fibrillation (NOAF) in critically ill patients, including both surgical and non-surgical intensive care unit settings, was evaluated in a 2024 systematic review. The included studies comprised 17 publications reporting on 324 patients, with 103 from non-surgical ICUs and 221 from post-surgical (non-cardiac) ICUs. Study designs included two randomized controlled trials, three retrospective comparative studies, and twelve case series. The primary endpoint was the rate of conversion to sinus rhythm following landiolol administration. The quality of the data was generally low, thus precluding meta-analysis, though risk-of-bias assessments using the ROBIN-E scale suggested no “high” risk for the primary endpoint. Across the body of evidence, landiolol demonstrated a consistent conversion rate to sinus rhythm, with mean rates of 75.7% in non-surgical ICU populations and 70.1% in surgical ICU cohorts. Conversion typically occurred within 1.8 to 9.1 hours of infusion initiation. In studies reporting heart rate metrics, landiolol treatment was associated with a 30–51% reduction in heart rate from baseline, with minimal impact on blood pressure. The most commonly used infusion rates ranged from 5 to 10 µg/kg/min, with surgical settings frequently employing doses up to 20 µg/kg/min. The median duration of landiolol therapy exceeded 24 hours in most reports. Hypotension occurred in approximately 13% of patients and was reversible upon dose adjustment or discontinuation. No cases of bronchospasm were documented. These findings suggest that landiolol is a viable option for rate or rhythm control in NOAF among critically ill patients, with a favorable hemodynamic profile and rapid onset of action, warranting further investigation through well-powered randomized controlled trials. [1]

A 2023 meta-analysis pooled data from 9 randomized controlled trials (RCTs) involving 868 adult patients undergoing cardiac surgery to evaluate the efficacy and safety of landiolol for the prevention of postoperative atrial fibrillation (POAF). Patients randomized to receive landiolol had a significantly lower incidence of POAF (12.2%, 56/460) compared with controls (32.6%; 133/408), with a relative risk (RR) of 0.40 (95% confidence interval [CI] 0.30 to 0.54) and an absolute risk difference (ARD) of 20.4% (95% CI 15.0 to 25.0). Landiolol was also associated with a shorter hospital length of stay in three trials (mean difference [MD], –2.32 days; 95% CI –4.02 to –0.57). No significant differences were observed in the incidence of bradycardia (RR 1.11; 95% CI 0.48 to 2.56) or in adverse outcomes such as mortality, myocardial infarction, congestive heart failure, or stroke. Notably, no cases of hypotension were reported among landiolol recipients. The authors assessed the certainty of evidence as moderate for POAF reduction due to indirectness (variability in outcome definitions) and low for length of stay due to imprecision and possible reporting bias. The review concludes that landiolol likely reduces POAF and may shorten hospitalization in this patient population, though further large-scale RCTs are required to confirm these findings. [2]

Another similar 2022 meta-analysis included 17 studies (13 RCTs and 4 cohort studies), totaling 1,349 patients undergoing cardiac, lung, or esophageal cancer surgeries. Landiolol was administered intravenously at doses ranging from 0.5 to 10 μg/kg/min, initiated during or shortly after anesthesia induction and continued for 24 to 72 hours postoperatively. The primary outcome was the incidence of POAF within the first postoperative week; secondary outcomes included postoperative complications, hospital length of stay, and all-cause mortality. Compared with control, landiolol significantly reduced the incidence of POAF (11% [66/598] vs. 25% [188/751]; OR 0.32; 95% CI 0.23 to 0.43; p<0.00001), with consistent benefit observed in esophageal (OR 0.38; 95% CI 0.18 to 0.78; p= 0.008) and cardiac surgery cohorts (OR 0.27; 95% CI 0.18 to 0.40; p<0.00001). The reduction in lung surgery patients did not reach statistical significance (OR 0.50; 95% CI 0.22 to 1.12; p= 0.09). Landiolol also decreased postoperative complications (OR 0.48; 95% CI 0.33 to 0.70; p= 0.0002) without significantly affecting hypotension or bradycardia. No statistically significant differences were observed in hospital length of stay or mortality. Low heterogeneity across studies and symmetric funnel plots suggested minimal publication bias. Overall, these findings support landiolol’s efficacy and safety profile for POAF prevention in diverse cardiothoracic surgical settings. [3]

A previous 2020 review also evaluated the clinical use of landiolol for rate control in patients with cardiac dysfunction and atrial fibrillation. The Japan Landiolol vs. Digoxin (J-Land) study, a multicenter RCT, demonstrated that landiolol was significantly more effective than digoxin in achieving the primary endpoint of heart rate <110 bpm and ≥20% reduction in heart rate within 2 hours (48% vs. 14%; p<0.001) in patients with left ventricular ejection fraction (LVEF) 25 to 50%, NYHA Class III or IV, and heart rate ≥120 bpm. Subgroup analyses confirmed this superiority across baseline variables including renal function, where landiolol also showed fewer adverse events in patients with eGFR <30 mL/min/1.73 m². Following these results, Japanese guidelines were revised to recommend landiolol as a Class IIa, Level B agent for acute heart failure with atrial fibrillation, while digoxin was downgraded to Level C. Post-marketing surveillance in 1,121 patients reported a 77.5% success rate in heart rate control with landiolol and a low hypotension incidence of 3%. Additional studies and case reports confirmed efficacy even in patients requiring inotropes, with no significant compromise in hemodynamics. Further prospective trials are ongoing to assess landiolol’s broader clinical implications. [4]

References:

[1] Levy B, Slama M, Lakbar I, et al. Landiolol for Treatment of New-Onset Atrial Fibrillation in Critical Care: A Systematic Review. J Clin Med. 2024;13(10):2951. Published 2024 May 17. doi:10.3390/jcm13102951
[2] Cafaro T, Allwood M, McIntyre WF, et al. Landiolol for the prevention of postoperative atrial fibrillation after cardiac surgery: a systematic review and meta-analysis. Le landiolol pour la prévention de la fibrillation auriculaire postopératoire après chirurgie cardiaque: une revue systématique et méta-analyse. Can J Anaesth. 2023;70(11):1828-1838. doi:10.1007/s12630-023-02586-0
[3] Hao J, Zhou J, Xu W, et al. Beta-Blocker Landiolol Hydrochloride in Preventing Atrial Fibrillation Following Cardiothoracic Surgery: A Systematic Review and Meta-Analysis. Ann Thorac Cardiovasc Surg. 2022;28(1):18-31. doi:10.5761/atcs.ra.21-00126
[4] Imamura T, Kinugawa K. Novel rate control strategy with landiolol in patients with cardiac dysfunction and atrial fibrillation. ESC Heart Fail. 2020;7(5):2208-2213. doi:10.1002/ehf2.12879

Literature Review

A search of the published medical literature revealed 6 studies investigating the researchable question:

What is the available evidence in using Rapibylk (landiolol), a fast-acting IV beta blocker, indicated for postop afib patients?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→



Please see Tables 1-6 for your response.


 

Landiolol hydrochloride for prevention of atrial fibrillation after coronary artery bypass grafting: New evidence from the PASCAL trial

Design

Randomized, double-blind, placebo-controlled study

N= 140

Objective

To investigate whether landiolol hydrochloride, an ultrashort-acting beta-blocker, could reduce postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting (CABG)

Study Groups

Landiolol group (n= 70)

Placebo group (n= 70)

Inclusion Criteria

Patients scheduled to undergo coronary artery bypass grafting on cardiopulmonary bypass

Exclusion Criteria

Patients with cardiogenic shock, sinus bradycardia (resting heart rate ≤ 50/min), second- or third-degree atrioventricular block, clinical hypothyroidism or hyperthyroidism, history of arrhythmia, and those undergoing off-pump surgery

Methods

Landiolol hydrochloride was administered at the time of central anastomosis during CABG at 2 mg/kg/min and discontinued after 48 hours. Continuous electrocardiographic monitoring was used to detect atrial fibrillation for 1 week post-surgery

Duration

1 week postoperatively

Outcome Measures

Primary: Occurrence/non-occurrence of atrial fibrillation up to 1 week postoperatively

Secondary: Operative mortality and complications, hemodynamics, fluid balance, ischemia-reperfusion injury parameters, inflammatory parameters, medical costs

Baseline Characteristics

 

Landiolol group (n= 70)

Placebo group (n= 70)

p-Value

Age, years

68.5 + 4.7 66.7 + 8.9

0.2423

Male

88.6% 94.3% 0.3660

euroSCORE

5.2 + 2.9 5.4 + 4.1 0.7746 

Diagnosis

          Acute myocardial infarction

          Old myocardial infarction

          Unstable angina

          Stable angina

 

8.6%

38.6%

37.1%

15.7% 

 

11.4%

34.2%

38.6%

15.7% 

0.7899

-

-

-

Emergency surgery

24.3% 27.1% 0.8469 
Ejection fraction, %

54.5 + 14.2

55.6 + 13.5

0.6598
Heart rate, beats/min

74.7 + 11.7

76.1 + 10.7

0.4518

Results

Endpoint

Landiolol group (n= 70)

Placebo group (n= 70)

p-Value

Occurrence of Af

10.0%

34.3%

0.0006

Days until Af

3.4 + 2.3

2.5 + 1.2

0.1556

Complications

4.3% 8.6%  0.4931

Hospital cost, $

35,679.48 + 6273.40

39,981.43 + 13,417.62

0.0202
Abbreviations: Af, atrial fibrillation

Adverse Events

Hypotension or bradycardia did not develop in any of the patients

Study Author Conclusions

Postoperative atrial fibrillation was reduced by treatment with landiolol hydrochloride. Improved ischemia, an anti-inflammatory effect, and inhibition of sympathetic hypertonia by landiolol presumably reduced the occurrence of atrial fibrillation. Landiolol hydrochloride could be useful in the perioperative management of patients undergoing cardiac surgery.

InpharmD Researcher Critique

The study was well-designed as a randomized, double-blind, placebo-controlled trial, providing strong evidence for the efficacy of landiolol in reducing postoperative atrial fibrillation. However, the study was limited to a single center and the sample size was relatively small, which may affect the generalizability of the findings. Additionally, the study did not compare landiolol with other beta-blockers or antiarrhythmic drugs, which could provide more comprehensive insights into its relative efficacy.



References:

Sezai A, Minami K, Nakai T, et al. Landiolol hydrochloride for prevention of atrial fibrillation after coronary artery bypass grafting: new evidence from the PASCAL trial. J Thorac Cardiovasc Surg. 2011;141(6):1478-1487. doi:10.1016/j.jtcvs.2010.10.045

 

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

Single-center, prospective randomized controlled, open-label, parallel study

N= 150

Objective To investigate the efficacy of prophylactic administration of low-dose landiolol on postoperative atrial fibrillation (POAF) in patients after cardiovascular surgery
Study Groups

Control group (no landiolol, n= 45)

1γ group (landiolol at 1 mcg/kg/min, n= 44)

2γ group (landiolol at 2 mcg/kg/min, n= 45)

Inclusion Criteria Consecutive patients aged ≥70 years who underwent elective cardiovascular surgery for valvular, ischemic heart, and aortic diseases
Exclusion Criteria Preoperative atrial fibrillation; hemoglobin A1c ≥8.0%; severe asthma (FEV1.0 <1000 ml); allergy to landiolol hydrochloride; emergency surgery; judged ineligible by physicians
Methods Patients were assigned to control, 1γ, or 2γ groups. Landiolol hydrochloride was administered intravenously for 4 days postoperatively in the 1γ and 2γ groups. Electrocardiography was continuously monitored. POAF was defined as continuous atrial fibrillation sustained for more than 5 minutes. Oral β-blockers were prohibited during the study period.
Duration April 2010 to June 2014
Outcome Measures

Occurrence of POAF between POD 1 and POD 4

Baseline Characteristics Characteristic Control (n= 45) 1 mcg/kg/min (n= 44) 2 mcg/kg/min (n= 45)
Female 16 (35.6%) 19 (43.2%) 18 (40.0%)
Age, years 74.5 ± 3.9 76.6 ± 3.5 75.9 ± 5.0
LVDd, mm 53.0 ± 9.0 49.0 ± 7.0 48.1 ± 6.4
LVEF, % 60.6 ± 12.2 66.8 ± 7.7 64.7 ± 10.4
LVDd left ventricular end-diastolic diameter, LVEF left ventricular ejection fraction
Results Category Control (n= 45) 1 mcg/kg/min (n= 44) 2 mcg/kg/min (n= 45) p-value
POAF incidence 11 (24.4%) 8 (18.2%) 5 (11.1%) 0.26
Female POAF incidence 7 (43.8%) 6 (31.6%) 1 (5.6%) 0.03
No preoperative ARBs POAF incidence 8 (53.3%) 3 (20.0%) 2 (10.5%) 0.02
Valve surgery POAF incidence 8 (50.0%) 1 (5.9%) 0 (0.0%) <0.01
Adverse Events Hypotension (3 patients in 1 mcg/kg/min group, 2 in 2 mcg/kg/min group); bradycardia (1 patient in 2 mcg/kg/min group)
Study Author Conclusions Prophylactic administration of low-dose landiolol may not be effective for preventing POAF in overall patients after cardiovascular surgery, but could be beneficial to female patients, patients not using ARBs preoperatively, and those after valvular surgery.
Critique The study was well-structured with a clear objective and methodology. However, being a single-center study with a relatively small sample size, the findings may not be generalizable. The inclusion of a significant proportion of thoracic endovascular aortic repair patients, who rarely developed POAF, might have underestimated the prophylactic effect of landiolol. Further multicenter studies are needed to validate these findings.
References:

Sasaki K, Kumagai K, Maeda K, et al. Preventive effect of low-dose landiolol on postoperative atrial fibrillation study (PELTA study). Gen Thorac Cardiovasc Surg. 2020;68(11):1240-1251. doi:10.1007/s11748-020-01364-9

 

Safety and Efficacy of Landiolol Hydrochloride for Prevention of Atrial Fibrillation after Cardiac Surgery in Patients with Left Ventricular Dysfunction: Prevention of Atrial Fibrillation After Cardiac Surgery With Landiolol Hydrochloride for Left Ventricular Dysfunction (PLATON) Trial

Design

Randomized, open-label study

N= 60

Objective

To investigate the safety and efficacy of landiolol hydrochloride in preventing atrial fibrillation after cardiac surgery in patients with left ventricular dysfunction

Study Groups

Landiolol group (n= 30)

Control group (n= 30)

Inclusion Criteria

Patients undergoing cardiac surgery under cardiopulmonary bypass with left ventricular dysfunction (ejection fraction ≤35%)

Exclusion Criteria

Patients with sinus bradycardia (HR ≤50 beats/min), second- or third-degree atrioventricular block, clinical hypothyroidism or hyperthyroidism, history of arrhythmia, surgery with circulatory arrest or left ventriculotomy, and planned off-pump surgery

Methods

Patients with left ventricular ejection fraction ≤35% undergoing cardiac surgery were randomly assigned to receive intravenous (IV) landiolol hydrochloride or no beta-blocker (control). In the intervention group, landiolol hydrochloride infusion was initiated at 2 μg/kg/min upon weaning from cardiopulmonary bypass and continued for a minimum of 2 days.

Oral beta-blocker therapy was introduced once oral intake was feasible; if initiated by postoperative day (POD) 3, landiolol was tapered to 1 μg/kg/min and discontinued one hour later. If oral therapy was delayed beyond POD 3, tapering and discontinuation of landiolol followed the actual initiation of the oral agent. 

Duration

Intervention: Two to five days

Follow-up: Seven days post-surgery

Outcome Measures

Primary: Occurrence of postoperative atrial fibrillation (POAF)

Secondary: Blood pressure, heart rate (HR), intensive care unit (ICU) and hospital stays, ventilation time, ejection fraction, biomarkers of ischemia, and brain natriuretic peptide

Baseline Characteristics

 Characteristic

Landiolol group (n= 30)

Control group (n= 30)

 

Age, years

64.8 ± 9.6 68.3 ± 9.4  

Female, n

 

Diabetes mellitus, n

16 13  

Hypertension, n

23 19  

Hyperlipidemia, n

12 17  
Obesity, n 6 3  
Smoking, n 16 14  
Chronic renal failure, n 13 19  
Ejection fraction 28.6 ± 7.3 28.6 ± 6.0  

Results

Endpoint

Landiolol group (n= 30)

Control group (n= 30)

p-value

Occurrence of POAF

3 (10%) 12 (40%) 0.002

Hospital stay, days, median

12.0 14.0 0.029

In the evaluation of secondary endpoints, postoperative HR was significantly lower in the landiolol group at multiple time points, including ICU arrival (p= 0.012) and postoperative days 1 through 3 and week 1 (p-values ranging from 0.001 to 0.018), despite no significant differences in preoperative HR or postoperative blood pressure.

Among ischemic biomarkers, troponin-I levels were significantly reduced in the landiolol group on postoperative day 1 (p= 0.022), and heart fatty acid–binding protein was significantly lower immediately postoperatively (p= 0.012), although creatine kinase MB levels did not differ. High-sensitivity C-reactive protein was significantly lower in the landiolol group at postoperative week 2 (p= 0.045), and brain natriuretic peptide levels were consistently reduced from postoperative day 1 through month 1 (all p< 0.05). While ICU length of stay was similar between groups, the landiolol group had a significantly shorter hospital stay (median 12.0 vs 14.0 days; p= 0.029).

Adverse Events

IV infusion was not discontinued for hypotension or bradycardia in either group.

Study Author Conclusions

Low-dose infusion of landiolol hydrochloride prevented atrial fibrillation after cardiac surgery in patients with cardiac dysfunction and was safe, with no effect on blood pressure. This intravenous β-blocker seems useful for perioperative management of cardiac surgical patients with left ventricular dysfunction.

InpharmD Researcher Critique

The study demonstrated the efficacy of landiolol in preventing POAF without causing hypotension or bradycardia. However, the open-label design and small sample size may limit the generalizability of the findings. Future blinded studies could provide more robust evidence.



References:

Sezai A, Osaka S, Yaoita H, et al. Safety and efficacy of landiolol hydrochloride for prevention of atrial fibrillation after cardiac surgery in patients with left ventricular dysfunction: Prevention of Atrial Fibrillation After Cardiac Surgery With Landiolol Hydrochloride for Left Ventricular Dysfunction (PLATON) trial. J Thorac Cardiovasc Surg. 2015;150(4):957-964. doi:10.1016/j.jtcvs.2015.07.003

 

Effects of Landiolol on Macrocirculatory Parameters and Left and Right Ventricular Performances Following Cardiac Surgery: A Randomized Controlled Trial

Design

Prospective, randomized, double-blind study

N= 58

Objective

To investigate the dose-dependent hemodynamic and metabolic effects of landiolol in the early postoperative period to reduce postoperative atrial fibrillation (POAF) incidence

Study Groups

Landiolol group (n= 30)

Control group (n= 28)

Inclusion Criteria

Adult patients scheduled for elective cardiac surgery with cardiopulmonary bypass

Exclusion Criteria

Preoperative permanent atrial fibrillation, contraindication to beta-blockers, circulatory shock, distributive shock, acute respiratory distress syndrome, major postoperative bleeding, pregnancy

Methods

Patients were randomized in a 1:1 ratio to receive either intravenous (IV) landiolol or placebo within two hours of intensive care unit admission. Landiolol was administered in a stepwise, dose-escalating regimen of 0.5, 1, 2, 5, and 10 µg/kg/min (equivalent to 0.03, 0.06, 0.12, 0.3, and 0.6 mL/kg/h based on a 1 mg/mL dilution), with each infusion level maintained for 20 minutes (five half-lives of the drug) to allow for stabilization.

Hemodynamic interventions, including changes in sedation, fluid therapy, vasopressors, or inotropes, were prohibited during the study period. If heart rate (HR) dropped below 60 bpm or mean arterial pressure below 65 mmHg, the infusion was discontinued. Echocardiographic assessments and macrocirculatory parameters were collected at baseline and after the final dose. Oral beta-blocker therapy (bisoprolol) was initiated on postoperative day one for all patients. 

Duration

January to November 2019

Outcome Measures

Primary: Effects of incremental doses of landiolol on macrocirculatory parameters (HR, blood pressure, stroke volume, echocardiographic variables)

Secondary: Effects on metabolic parameters (central venous oxygen saturation [SvO2], lactate) and POAF incidence

Baseline Characteristics

 

Placebo (n= 29)

Landiolol (n= 30)

p-value

Age, years

64 ± 10 63 ± 11 0.51

Male

21 (72%) 23 (77%) 1.0

Weight, kg

79 ± 19 77 ± 12 0.64

BMI, kg/m²

27.4 ± 5.4 26.1 ± 3.2 0.24

Diabetes mellitus

3 (10%) 5 (17%) 0.74

Hypertension

20 (69%) 16 (53.3%) 0.34

Chronic renal failure

4 (14%) 5 (17%) 1.0

Peripheral arterial disease

3 (10%) 2 (7%) 0.97

Chronic medications

Beta-blockers

ACEi/ARB

Statins

Platelet inhibitors

 

4 (14%)

14 (48%)

13 (45%)

15 (52%)

 

4 (13%)

13 (43%)

14 (47%)

12 (40%)

 

0.96

0.52

0.89

0.37

Type of surgery

Valvular replacement or repair

Coronary bypass

 

21 (73%)

5 (17%)

 

15 (50%)

10 (33%)

 

0.08

0.27

Hemoglobin, g/L (IQR)

123 (118 to 129)

122 (110 to 132)

0.42

Preoperative LVEF (IQR)

49 (40 to 63)

50 (43 to 56)

0.94

Abbreviations: BMI, body mass index; ACEi, angiotensin-converting enzyme inhibitors; ARB, angiotensin-receptor blocker; IQR, interquartile range

Results

The administration of incremental doses of landiolol (0.5 to 10 µg/kg/min) resulted in a significant reduction in HR compared to placebo (p< 0.01), with no significant changes observed in mean arterial pressure, indexed stroke volume, or pulse-pressure variation. Echocardiographic measures of left and right ventricular function were largely comparable between groups, except for the mitral E/A ratio, which was significantly higher in the landiolol group at the final timepoint (1.2 [0.9 to 1.4] vs. 0.9 [0.7 to 1.1]; p= 0.02). Other indices, including ejection fraction, velocity-time integral, tricuspid annular plane systolic excursion, and fractional area change, showed no significant differences.

SvO₂ increased over time in the landiolol group (74% [68 to 79] at T10 vs. 65% [60 to 71] at baseline; p< 0.01), with no significant between-group difference at baseline (p= 0.19). Arterial lactate levels were not significantly different between groups at either baseline (1.7 [1.4 to 2.2] mmol/L for landiolol vs. 1.9 [1.4 to 2.3] mmol/L for placebo) or at T10 (2.0 [1.7 to 2.4] vs. 1.4 [1.2 to 2.2] mmol/L). Postoperative atrial fibrillation occurred in 5 patients (17%) in the landiolol group and in 9 patients (32%) in the placebo group (p= 0.285).

Adverse Events

No significant adverse events reported.

Study Author Conclusions

Infusion of landiolol in the range of 0.5-to-10 mg/kg/min during the early postoperative period presents a good macrohemodynamic safety profile in cardiac surgical patients and could be useful to prevent POAF.

InpharmD Researcher Critique

The study provided detailed insights into the hemodynamic effects of landiolol, demonstrating its safety in controlling postoperative HR without significant adverse effects. However, the study was limited by its small sample size and the exclusion of more severe patients, which may limit the generalizability of the findings. Additionally, the study was underpowered to show a significant decrease in POAF incidence.



References:

Ferraris A, Jacquet-Lagrèze M, Cazenave L, et al. Effects of Landiolol on Macrocirculatory Parameters and Left and Right Ventricular Performances Following Cardiac Surgery: A Randomized Controlled Trial. J Cardiothorac Vasc Anesth. 2022;36(8 Pt B):2864-2869. doi:10.1053/j.jvca.2022.02.016

 

Characteristics of Included Single-Centred Randomized Controlled Trials
Authors Country Design Type of surgery No. of patients Treatment group(s) Comparison group Follow-up Ascertainment of POAF
Sezai et al. 2015 Japan Blinded CABG 60 Landiolol infusion 2 ug/kg–1·min–1. From induction to first dose of oral beta blocker (min 48 hr infusion to max 120 hr infusion). Nonadministration of landiolol 7 days Continuous ECG monitoring from POD 0 to POD 7. Control log assessed by physician. AF lasting ≥ 5 min or affected hemodynamics requiring treatment.
Sezai et al. 2012 Japan Blinded CABG 68 Landiolol infusion 5 ug/kg–1·min–1. From induction to 72 hr postop. Titrated for HR of 60–90 bpm. Nonadministration of landiolol 7 days Continuous ECG monitoring from POD 0 to POD 7. Control log assessed by physician. AF lasting ≥ 5 min or affected hemodynamics requiring treatment.
Sezai et al. 2011 Japan Blinded CABG 140 Landiolol infusion 2 ug/kg–1·min–1. From induction to 48 hr postop. Titrated for HR of 60–90 bpm. Saline placebo 7 days Continuous ECG monitoring from POD 0 to POD 7. Control log assessed by physician. AF lasting ≥ 5 min or affected hemodynamics requiring treatment.
Ferraris et al. 2021 France Blinded CABG 59 Landiolol perfusion over 120 min in incremental doses: 0.5, 1, 2, 5 and 10 µg/kg–1·min–1 Saline placebo 5 days NA
Fuji et al. 2012 Japan   CABG (off-pump) 70 Landiolol infusion between 0–10 ug·kg–1·min–1. From ICU admission to induction to first dose of oral beta blocker (50-hr infusion). Titrated for HR of 60–80 bpm. Nonadministration of landiolol 7 days Continuous ECG monitoring from POD 0 to POD 7. AF defined as irregular narrow complex rhythm with an absence of a discrete P wave lasting for ≥ 10 min or required treatment for hemodynamic deterioration.
Sakaguchi et al. 2012 Japan   CABG + valve, valve replacement, 60 Landiolol infusion 10 ug/kg–1·min–1. From admission to ICU to 72 hr postop. Titrated for HR of 60 bpm. Nonadministration of landiolol 3 days Continuous ECG monitoring from POD 0 to POD 3. AF lasting for ≥ 1 min.
Osada et al. 2012 Japan   CABG, valve, thoracic aorta surgery, bypass grafting + valve 141 Landiolol infusion 1 ug/kg–1·min–1. From ICU admission to 48 hr postop. Nonadministration of landiolol NA Osada et al. 2012
Ogawa et al. 2012 Japan Blinded Isolated off-pump CABG 136 Landiolol infusion between 3–5 ug/kg–1·min–1. From induction to 48 hr postop. Titrated for HR of 60–90 bpm. Nonadministration of landiolol 7 days Continuous ECG monitoring from POD 0 to POD 7. AF lasting for ≥ 10 min. Confirmed by physician.
Sasaki et al. 2020 Japan Blinded Cardiac 134

Group 1: Landiolol infusion 1 ug/kg–1·min–1. From ICU admission to 96 hr postop.

Group 2: Landiolol infusion 2 ug/kg–1·min–1. From ICU admission to 96 hr postop.

Nonadministration of landiolol 4 days Continuous ECG monitoring from POD 0 to POD 4. AF lasting ≥ 5 min, diagnosed by cardiologist.
Abbreviations: AF, atrial fibrillation; BPM, beats per minute; CABG, coronary bypass graft; ECG, electrocardiogram; HR, heart rate; ICU, intensive care unit; min, minute; POAF,  postoperative atrial fibrillation; POD, postoperative day



References:

Adapted from:
Cafaro T, Allwood M, McIntyre WF, et al. Landiolol for the prevention of postoperative atrial fibrillation after cardiac surgery: a systematic review and meta-analysis. Le landiolol pour la prévention de la fibrillation auriculaire postopératoire après chirurgie cardiaque: une revue systématique et méta-analyse. Can J Anaesth. 2023;70(11):1828-1838. doi:10.1007/s12630-023-02586-0

 

Characteristics of Included Studies Evaluating Landiolol Hydrochloride in Preventing Atrial Fibrillation Following Cardiothoracic Surgery 
Author, year Country No. of patients Age (yrs) Control Age (yrs) Landiolol Type of surgery Initial dose of landiolol Start of landiolol Duration of use of landiolol (landiolol group) Primary outcome Secondary outcome
Aoyama, 2016 JPN 50 66.9 ± 8.9 67.4 ± 8.7 VATS: 36
Open: 14
5 μg/kg/min During general anesthesia NA Incidence of AF until 7 POD Plasma concentration of IL-6, serum Mg, serum Ca, CRP, NT Pro-BNP by blood sampling, three fractions of catecholamines (adrenaline, noradrenaline, and dopamine)
Okita, 2008 JPN 301 NA NA   5 μg/kg/min Before surgery NA Incidence of AF until 2 POD NA
Nojiri, 2011 38) JPN 30 69.5 ± 7.3 72.2 ± 5.7 VATS: 18
Open: 12
10 patients received 5 μg/kg/min; 5 received 10 μg/kg/min Before surgery 24 h Incidence of AF until 2 POD Bradycardia, hypotension, congestive heart failure, myocardial infarction, angina pectoris, pneumonia, acute respiratory failure, respiratory insufficiency requiring tracheostomy, respiratory failure requiring mechanical ventilation, atelectasis with bronchoscopic therapy, home oxygen treatment, thromboembolic events, death
Horikoshi, 2017 JPN 39 63 ± 8 67 ± 7 Esophagectomy 5 μg/kg/min Before surgery 20.5 ± 7.5 h Incidence of AF until 2 POD Amount of bleeding, infusion volume of crystalloid, blood transfusion volume, urine volume, Hb after surgery, length of hospital stay
Ojima, 2017 JPN 100 69 (45–83) 68 (31–85) Thoracoscopic oesophagectomy: 99 transthoracic 3 μg/kg/min After surgery 72 h Incidence of AF between 1 and 7 POD Rate of occurrence of AF in the hospital, postoperative complications, hemodynamic performance, changes in inflammatory markers
Yoshida, 2017 JPN 79 62 (45–82) 64 (48–79) VATS 5 μg/kg/min Before surgery 24 h Incidence of AF until 2 POD Anastomotic leakage, pneumonia, recurrent nerve palsy, ileus, chylothorax, over 38° of body temperature
Aoki, 2020 JPN 56 69 (60–71) 68 (62–74) Esophagectomy 3 μg/kg/min Before surgery 24 h Incidence of AF until 4 POD The proportion of patients whose AF appeared within 24 h, other complications based on the Clavien–Dindo classification, the intensive care unit, hospital stays
Sakaguchi, 2012 JPN 60 68.7 ± 10.0 69.3 ± 8.6 CABG: 0
Valve: 55
CABG + valve: 4
Aortic root
10 μg/kg/min After surgery 72 h Incidence of AF until 2 POD HR, systemic blood pressure, cardiac index, average pulmonary arterial blood pressure
Fujii, 2012 JPN 70 68.5 NA OPCABS 100% 5 μg/kg/min After surgery 50 h Incidence of AF until 7 POD Hospital mortality, HR, BP, fluid balance
Fujiwara, 2009 JPN 55 69.2 ± 7.6 69.9 ± 9.1 CABG 1.5–2.5 μg/kg/min After CPB 48 h Incidence of AF Cardiac index, dose of inotropic agents, intubation time, length of ICU stay, postoperative LVEF
Nagaoka, 2014 JPN 45 69 ± 6.3 67 ± 8.5 CABG 0.5 μg/kg/min After surgery 38.4 ± 16.8 h Incidence of AF until 7 POD HR, SBP obtained from an arterial line, CI, SPA, PCWP, SVI
Nakanishi, 2013 JPN 105 65.7 ± 12.6 67.2 ± 11.5 CABG: 55
Valve: 50
1 μg/kg/min Before surgery 23.9 ± 32 h Incidence of AF HR, length of ICU stay, time to extubation, postoperative complications
Ogawa, 2013 JPN 136 71.6 ± 7.8 69.3 ± 6.3 CABG 3–5 μg/kg/min Before surgery 72 h Incidence of AF until 7 POD Postoperative levels of troponin I, CK-MB isoenzyme, and CRP
Sakamoto, 2012 JPN 71 69.3 ± 8.4 70.2 ± 10.6 CABG: 25
VR: 25
CABG + VR: 9
Others: 12
0.5–2 μg/kg/min After surgery 72 h Incidence of AF until 3 POD Hospital mortality, HR, BP, fluid balance
Sezai, 2011 JPN 140 66.7 ± 8.9 68.5 ± 4.7 CABG 2 μg/kg/min During surgery 48 h Incidence of AF until 7 POD Operative mortality and complications; hemodynamics at the return to the ICU at 12, 24, and 48 h after administration and at 24 hours after discontinuing administration; fluid balance; CK-MB isoenzyme; troponin-I and human heart fatty acid-binding protein; IL-6, IL-8, and hs-CRP; urinary 8-hydroxydeoxyguanosine; total cost of hospital treatment
Sezai, 2012 JPN 68 68.2 ± 7.5 68.5 ± 9.6 CABG 5 μg/kg/min During surgery 72 h Incidence of AF until 7 POD Operative mortality and complications, SBP and diastolic BP and HR, CK-MB isoenzyme, troponin-I, and human heart fatty acid-binding protein, hs-CRP, PTX-3, ADMA, and BNP
Sezai, 2015 JPN 60 68.3 ± 9.4 64.8 ± 9.6 CABG: 46 Valve: 12
CABG + Valve: 2
2 μg/kg/min During surgery 48 h Incidence of AF until 8 POD Operative mortality and complications, SBP and diastolic BP and HR, CK-MB isoenzyme, troponin-I, and human heart fatty acid-binding protein, hs-CRP, PTX-3, ADMA, and BNP
Abbreviations: JPN: Japan; CPB: cardiopulmonary bypass; VATS: video-assisted thoracic surgery; Valve: heart valve surgery; CABG: coronary artery bypass grafting; OPCABS: off pump coronary artery bypass surgery; AF: atrial fibrillation; POD: postoperative day; BP: blood pressure; HR: heart rate; LVEF: left ventricular ejection fraction; M: male; F: female; NA: not applicable; IL-6: interleukin-6; Mg: magnesium; Ca: calcium; CRP: C-reactive protein; NT Pro-BNP: N-terminal pro-brain natriuretic peptide; Hb: hemoglobin; ICU: intensive care unit; SBP: systolic blood pressure; CT: cardiac index; SPA: systolic pulmonary artery pressure; PCWP: pulmonary capillary artery wedge pressure; SVI: stroke volume index; CK-MB: creatine kinase-MB; hs-CRP: high-sensitivity C-reactive protein; PTX-3: pentraxin-3; ADMA: asymmetric dimethylarginine; BNP: brain natriuretic peptide; VR: valve replacement



References:

Adapted from:
Hao J, Zhou J, Xu W, et al. Beta-Blocker Landiolol Hydrochloride in Preventing Atrial Fibrillation Following Cardiothoracic Surgery: A Systematic Review and Meta-Analysis. Ann Thorac Cardiovasc Surg. 2022;28(1):18-31. doi:10.5761/atcs.ra.21-00126