Ivabradine approved and other uses in clinical practice: a systematic review

Heart rate (HR) stands as a prognostic indicator of cardiovascular disease and a modifiable risk factor in heart failure (HF). Medication intolerance can curtail the application of conventional HR-lowering β-blockers to the optimum target dose. Ivabradine (IVA), a specific negative-chronotropic agent, selectively inhibits I f current in pacemaker cells of the sinoatrial node without depressing myocardial contractility or comprising hemodynamics. This review summarized ivabradine’s clinical labeled and off-label uses, and mechanism of action focusing on the clinical outcomes. PubMed was searched up to January 2024 using the main keywords of IVA, coronary artery disease (CAD), HF, postural orthostatic tachycardia syndrome (POTS) and tachyarrhythmia. To comprehensively review IVA’s clinical indications, mechanisms, and therapeutic effects, all studies investigating treatment with IVA in humans were included, comprising different types of studies such as randomized controlled trials (RCTs) and longitudinal prospective observational studies. After screening, 141 studies were included in our review. A large number of reviewed articles were allocated to HFrEF and CAD, suggesting IVA as an alternative to β-blockers in case of contraindications or intolerance. The beneficial effects of IVA as premedication for coronary computed tomography angiography, HR lowering in POTS, and inappropriate sinus tachycardia constituted most studies among off-label uses. Promising results have been reported on the efficacy of IVA in controlling HR, especially in patients with inappropriate sinus tachycardia or POTS. Due to the unique mechanism of action, IVA has the potential to be used more frequently in future clinical practice.