Clin Ther. 2020 Dec;42(12):2289-2297.e0. doi: 10.1016/j.clinthera.2020.10.005. Epub 2020 Nov 5.
PURPOSE: Ivabradine reduces heart rate (HR) in patients with heart failure (HF). However, its effect on cardiac remodeling is not obvious. The goal of this study was to explore the extra effect of ivabradine on cardiac remodeling in patients with HF.
METHODS: We searched PubMed from database inception to January 31, 2020, Cochrane and Embase from database inception to February 2, 2020, and Web of Science and ClinicalTrials.gov from database inception to February 3, 2020, for randomized controlled trials on ivabradine treatments in patients with stable symptomatic HF, left ventricular ejection fraction (LVEF) < 45%, and resting HR ≥ 60 beats/min in sinus rhythm. We pooled the mean differences (MDs) or standardized mean differences and their 95% CIs. An inverse variance was used to combine data. Fixed- or random-effects models were used to outline the outcomes based on heterogeneity levels. We assessed the heterogeneity among studies according to the I2 statistic. A sensitivity analysis for select results was performed to assess the robustness of the outcomes.
FINDINGS: Of 2277 trials, 9 trials fulfilled the inclusion criteria. A total of 1523 patients were enrolled in 9 studies. There were 796 participants in the ivabradine group and 727 participants in the control group. The duration of follow-up ranged from 6 weeks to 19.6 months. The mean (SD) age of the participants was 59.7 (11.2) years, and 1187 participants (77.9%) were men. Therapy with ivabradine was related to reversing cardiac remodeling with a significant increase in LVEF (MD = 3.04%; 95% CI, 2.07%-4.00%; p < 0.001), decrease in the left ventricular end-systolic volume index (LVESVI) (MD = -7.30 mL/m2; 95% CI, -12.94 to -1.66 mL/m2; p = 0.01), and reduction in the left ventricular end-diastolic volume index (LVEDVI) (MD = -7.27 mL/m2; 95% CI, -14.04 to -0.50 mL/m2; p = 0.04). In the subgroup of enrolled patients with a resting HR of ≥70 beats/min, greater progress in LVEF was detected in the ivabradine group (MD = 3.60%; 95% CI, 2.40%-4.81%; p < 0.001), and a higher improvement in LVESVI was identified in the ivabradine group (MD = -11.06 mL/m2; 95% CI, -21.15 to -0.98 mL/m2; p = 0.03).
IMPLICATIONS: In patients with stable symptomatic HF, LVEF <45%, and resting HR ≥ 60 beats/min in sinus rhythm, ivabradine use was associated with reversing cardiac remodeling with a significant increase in LVEF, a decrease in LVESVI, and a reduction in LVEDVI.