The prevalence of heart failure with preserved ejection fraction (HFpEF) is about 30-75% of the patients living with heart failure. A hallmark symptom of these patients is exercise intolerance. Ivabradine can, eventually, increase exercise capacity by heart rate control. However, clinical trials show conflicting results about the effects of ivabradine on exercise capacity, an important prognostic variable. The aim of this study was to investigate the effects of ivabradine on exercise capacity in individuals with HFpEF. This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and supplemented by guidance from the Cochrane Collaboration Handbook for Systematic Reviews of Interventions. For the meta-analysis, a forest plot was used to graphically present the effect sizes and the 95% CIs. Four randomized controlled trials were included. Ivabradine did not change exercise capacity expressed by peak VO and 6MWT (MD = 0.8; 95% CI - 2.5 to 4.3; P = 0.62) (Fig. 4a). In our secondary analysis, the ivabradine group showed a significant resting HR reduction when compared with placebo (MD = - 13.2; 95% CI - 16.6 to -9.8; P < 0.00001) and ivabradine showed increased values of E/e' ratio compared with placebo (MD = 0.8; 95% CI 0.0 to 1.6; P = 0.04). Current available evidence suggests that there is no effect of ivabradine on exercise capacity in patients with HFpEF. Also, questions about negative effects on E/e' values and adverse events associated with ivabradine treatment need to be considered in future studies.
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