A Systematic Review and Meta-Analysis of Randomised Controlled Trials Assessing Clinical and Haemodynamic Outcomes of Ivabradine in Heart Failure With Reduced Ejection Fraction Patients

Background: Ivabradine, a pure bradycardic agent, can be given to heart failure reduced ejection fraction (HFrEF) patients with a sinus rhythm of ≥70 bpm on a maximum beta blocker dose, or when beta blockers are contraindicated. This study aimed to see how ivabradine affects the clinical and haemodynamic outcomes of HFrEF patients. Methods: This systematic review and meta-analysis searched ClinicalTrials.gov, OpenMD, ProQuest, PubMed, and ScienceDirect for potential articles. All relevant data were extracted. For all pooled effects, the random effect model was applied. Results: A total of 18,972 heart failure (HF) patients from nine randomised clinical trials (RCTs) were involved in this study. Ivabradine decreased the risk of HF mortality (RR 0.79; 95% CI 0.64–0.98; p=0.03) and HF hospitalisation (RR 0.80; 95% CI 0.65–0.97; p=0.03). Ivabradine was related to a greater reduction in heart rate (MD -12.21; 95% CI -15.47 – -8.96; p<0.01) and left ventricular ejection fraction (LVEF) improvement (MD 3.24; 95% CI 2.17–4.31; p <0.01) compared with placebo. Asymptomatic bradycardia (RR 4.25; 95% CI 3.36–5.39; p<0.01) and symptomatic bradycardia (RR 3.99; 95% CI 3.17–5.03; p<0.01) were higher in the ivabradine group. Conclusion: Ivabradine can reduce the risk of HF mortality and HF hospitalisation in HFrEF patients. Ivabradine also effectively reduces resting heart rate and improves LVEF. However, ivabradine is associated with a greater risk of symptomatic and asymptomatic bradycardia.