Ivabradine in the Treatment of POTS Before and After COVID-19 Pandemic: A Systematic Review and Meta-Analysis

Postural orthostatic tachycardia syndrome (POTS) is a debilitating autonomic disorder characterized by excessive orthostatic tachycardia and significant functional impairment. Conventional therapies, including beta-blockers, often provide incomplete relief or are poorly tolerated. Ivabradine, a selective If channel inhibitor, reduces heart rate without affecting blood pressure or myocardial contractility, making it a promising option, particularly in post-COVID-19 POTS. This systematic review and meta-analysis evaluated the efficacy and safety of ivabradine in patients with POTS. PubMed, Embase, and the Cochrane Library were searched through August 2025 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD420251073600). Eligible studies included randomized controlled trials, observational studies, and case series reporting ivabradine outcomes in POTS. Primary outcomes were changes in standing and supine heart rate; secondary outcomes included symptom burden, quality of life, and adverse events. A random-effects model was used, heterogeneity was assessed through sensitivity analyses, and certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation. Nine studies involving 245 patients were included. Ivabradine significantly reduced standing heart rate (-18.5 bpm; 95% confidence interval -23.3 to -13.8) and supine heart rate (-9.7 bpm; 95% confidence interval -13.4 to -6.1). Symptom improvement particularly palpitations, lightheadedness, and exercise intolerance was consistently reported across classic, pediatric, hyperadrenergic, and post-COVID-19 subgroups. Adverse events were infrequent and mild, most commonly transient visual disturbances, with no reports of severe bradycardia or hypotension. Heterogeneity was high, largely driven by pediatric and post-COVID-19 cohorts. In conclusion, ivabradine seems to provide meaningful heart rate reduction and symptomatic improvement in POTS with a favorable safety profile. However, evidence is limited by small, heterogeneous, predominantly observational studies, underscoring the need for large, multicenter randomized controlled trials.