Abstract
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.
Key words
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Article info
Publication history
Published online: November 04, 2020
Accepted:
September 16,
2020
Identification
Copyright
© 2020 Elsevier Inc.
