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]