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) < 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) < 0.01) and symptomatic bradycardia (RR 3.99; 95% CI 3.17-5.03; p<0.01) < 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 risk of symptomatic and asymptomatic bradycardia.