Complementary and Synergic Role of Combined Beta-blockers and Ivabradine in Patients with Chronic Heart Failure and Depressed Systolic Function: A New Therapeutic Option?

While substantial advances have been made in the treatment of chronic heart failure (CHF) in the past decade, the prevalence of CHF is increasing. CHF represents a growing financial burden on healthcare systems and, despite therapeutic advances, mortality remains high. There is a need for new therapeutic targets and treatment strategies. Beta-blockers remain the drugs of choice for reducing heart rate (HR) in CHF with reduced ejection fraction (EF), but evidence suggests that their use is suboptimal; a substantial proportion of patients with heart failure do not tolerate the doses of beta-blockers used in the large clinical trials and more than half of patients have inadequately controlled HR. For these patients, clinical evidence supports the addition of ivabradine to beta-blocker therapy. Ivabradine reduces HR via a different mechanism to beta-blockers and has been recommended in European Society of Cardiology guidelines to reduce the risk of CHF hospitalisation and cardiovascular death in symptomatic patients with EF ≤35 % who are in sinus rhythm and have a resting HR ≥70 beats per minute despite treatment with an evidence-based therapy. In addition to HR-lowering, ivabradine exerts other effects on the myocardium that are synergic and complementary to beta-blockers, and may be beneficial in CHF syndrome. In this review we summarise current findings on ivabradine therapy in CHF and advance the hypothesis, with related rationale, for combining ivabradine and beta-blocker therapy from the early stages of CHF in patients with reduced EF as an alternative strategy to up-titration of beta-blockers to an optimal dose.