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

Abstract

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

Methods: Consecutive 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.

Results: POAF 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).

Conclusions: These 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.

Keywords: Cardiovascular surgery; Landiolol hydrochloride; Low dose; Postoperative atrial fibrillation; Prophylactic administration.

Fig. 1

Clinical trial flowchart. PELTA study was composed of 150 patients who underwent cardiovascular surgery. HbA1c hemoglobin A1c, FEV1.0 forced expiratory volume in 1 s, γ μg/kg/min

Fig. 2

Preventive effects of landiolol for postoperative atrial fibrillation among all patients and subgroups. The black dots and bars represent the odds ratio and 95% confidence intervals, respectively. a All patients, b female patients, c patients not using ARBs prior to cardiovascular surgeries, d patients who underwent valvular surgery. Multivariate logistics regression was conducted after adjustment for age, left ventricular end-diastolic diameter, and left ventricular ejection fraction. The dose–response relationship was examined with the Cochran–Armitage test for trend. Due to quasi-complete separation in the logistics regression, the prophylactic effect of landiolol on postoperative atrial fibrillation after valvular surgeries was investigated in a composite 1γ + 2γ group. γ μg/kg/min, ARBs angiotensin II receptor blockers

Fig. 3

Time course of changes in echocardiographic and blood biochemical data. a LAD, b LVDd, c LVEF, d BNP, e WBC. All p values were evaluated by one-way repeated analysis of variance. Values in a, b, c, and e are mean ± standard deviation. Values of BNP are graphed as box-and-whisker plot in the appropriate format. γ μg/kg/min, LAD left atrial diameter, LVDd left ventricular end-diastolic diameter, LVEF left ventricular ejection fraction, BNP brain natriuretic peptide, WBC white blood cell, Pre preoperative day, POD postoperative day

Fig. 3

Time course of changes in echocardiographic and blood biochemical data. a LAD, b LVDd, c LVEF, d BNP, e WBC. All p values were evaluated by one-way repeated analysis of variance. Values in a, b, c, and e are mean ± standard deviation. Values of BNP are graphed as box-and-whisker plot in the appropriate format. γ μg/kg/min, LAD left atrial diameter, LVDd left ventricular end-diastolic diameter, LVEF left ventricular ejection fraction, BNP brain natriuretic peptide, WBC white blood cell, Pre preoperative day, POD postoperative day