Abstract
Ivabradine is thought to be highly effective in the treatment of heart failure through its effects on heart rate (HR) and left ventricular ejection fraction (LVEF). However, its effectiveness on other clinical outcomes and cardiovascular parameters is undetermined. Therefore, a meta-analysis of existing clinical studies was conducted to determine the effectiveness of ivabradine in treating chronic heart failure. A primary search was employed using five databases, namely, PubMed, Medline, Clinical Trials, Embase, and Cochrane. A meta-analysis was conducted on 11 studies meeting the inclusion criterion, including randomized control trials of chronic heart failure patients receiving ivabradine versus standard care or placebo treatment. Non-human studies and studies without echocardiogram measures of ejection fraction, a placebo group, or follow-up data on readmission or mortality were restricted from the study; however, there were no restrictions on the date or duration of treatment. The outcomes measuring the effectiveness of the drug included cardiovascular mortality, hospital readmissions, and exercise capacity, in addition to changes in HR, LVEF, Minnesota Living with Heart Failure (MLWHF) questionnaire, N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP) levels, and left ventricular volume. The reduction in bradycardia and atrial fibrillation was also determined. Subsequently, data from 11 randomized clinical trials including 1,687 study participants, 862 in the ivabradine treatment group, and 825 in the placebo group were included in the analysis. No significant reduction in cardiovascular mortality or hospital readmissions was noted with the use of ivabradine compared to the placebo group (relative risk (RR)), 0.79 (95% confidence interval (CI)), 0.15, 4.14) and (RR, 0.53 (95 % CI, 0.20, 1.22), respectively. In 10 of these trials, there was a significant reduction in the HR of treatment participants (mean difference (MD)), - 11.7 (95 % CI, -12.88, -10.51). There was also a beneficial association noted between LVEF and ivabradine participants (MD, 3.03 (95 % CI, 2.07, 3.98). There was a significant reduction in NT-proBNP levels (MD, -384 (95 % CI, -581.68, -187.72) in ivabradine patients, but no significant change was noted in BNP levels in this group (MD, -72.32; 95 % CI, -263.67, 119.0) The risk reduction in bradycardia and atrial fibrillation among ivabradine users versus non-users were both insignificant (RR, 1.62 (95 % CI, 0.024, 4.83) and RR, 0.93 (95 % CI, 0.014, 12.51), respectively). Conclusively, heart failure patients taking ivabradine demonstrated significant improvements in LVEF and reduction in HRs compared to the standard treatment group. No significant changes in other cardiovascular or clinical outcomes in Ivabradine users were confirmed in this meta-analysis.