Key result
Addition of ivabradine to standard heart failure therapy significantly reduced resting heart rate (MD -9.57) and improved left ventricular ejection fraction (MD 3.89) in patients with chronic HFrEF.
Why the study?
The effect of ivabradine on rehospitalization and cardiac function in chronic heart failure patients remained inconsistent.
Does the addition of ivabradine to standard heart failure therapy improve cardiac function and clinical outcomes in patients with chronic HFrEF?
Meta-Analysis (n=7,074)
Does the addition of ivabradine to standard heart failure therapy improve cardiac function and clinical outcomes in patients with chronic HFrEF?
Mean Difference: -9.57 (95% CI -11.15–-8)
Adding ivabradine to standard heart failure therapy in chronic HFrEF patients improves cardiac function, reduces resting heart rate, and lowers the risk of worsening HF readmission, though it does not reduce cardiovascular mortality.
Supports adding ivabradine in HFrEF with elevated HR; reinforces hospitalization and LVEF benefits from prior RCTs.
Elevated resting heart rate in chronic heart failure (HF) patients has been associated with higher mortality and poor prognosis. Ivabradine is a new pure bradycardic agent that has been used to treat angina or heart failure reduced ejection fraction (HFrEF) with sinus heart rate above 70 beats per minute. However, the effect of ivabradine for chronic HF patients on rehospitalization and cardiac function is still inconsistent. Thus, this meta-analysis aimed to elucidate the effect of Ivabradine in chronic HFrEF patients. We systematically searched PubMed, Medline, Clinical Trials.gov, and The Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) of ivabradine with search terms Ivabradine (MeSH Terms), chronic heart failure and beta-blocker. The primary endpoints of the study include the impact of Ivabradine on heart rate, left ventricle ejection fraction (LVEF), left ventricular remodeling, exercise capacity, and quality of life (QoL) in patients with chronic HFrEF. Secondary endpoints were safety analysis of Ivabradine including cardiovascular mortality, worsening HF readmission, visual disturbances, and asymptomatic bradycardia. The analysis was done by Review Manager 5.4 Analyzer, to analyze the mean differences (MD) for continuous data and risks ratio (RR) for dichotomous data. A total of six RCTs and one subgroup analysis showed add of Ivabradine to standard HF therapy was associated with greater resting heart rate reduction (MD = -9.57; 95% CI -11.15, -8.00), improved LVEF (MD = 3.89; 95% CI 2.61, 5.17), left ventricular reverse remodeling improvement (MD = -3.73; 95% CI -4.25, -3.21, LVESV; MD = -17.00, 95%CI -29.65, -4.35, LVEDD; MD = -1.43, 95%CI -2.78, -0.08, LVEDV; MD = -14.75, 95%CI -34.36, 4.87), increased exercise capacity (exercise duration; MD = 8.52; 95%CI 0.09, 16.94), and significant reduction on rehospitalization due to worsening HF (RR = 0.76, 95%CI 0.69, 0.84). However, Ivabradine has no significant effect on the quality of life (MD = 0.65; 95%CI -10.52, 11.82), and cardiovascular mortality (RR = 0.92; 95%CI 0.82, 1.03). Moreover, there were some events of visual disturbances and asymptomatic bradycardia observed in the Ivabradine group compared to the placebo group (RR = 4.76; 95%CI 3.03, 7.48; RR = 3.78; 95%CI 2.77, 5.15, respectively). Addition of Ivabradine to standard HF therapy is associated with cardiac function improvement, reduction on worsening HF readmission, greater HR reduction, and better exercise capacity in chronic HFrEF patients, although it cannot reduce cardiovascular mortality or improve the quality of life.
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Sasmita et al. (2021) conducted a meta-analysis in Chronic heart failure with reduced ejection fraction (HFrEF) (n=7,074). Ivabradine vs. Placebo or standard optimal medical treatment was evaluated on Resting heart rate reduction (MD -9.57, 95% CI -11.15, -8.00). Addition of ivabradine to standard heart failure therapy significantly reduced resting heart rate (MD -9.57) and improved left ventricular ejection fraction (MD 3.89) in patients with chronic HFrEF.
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