• Sunil T Mathew, Sunny S Po, and Udho Thadani.
• Department of Veterans Affairs Medical Center, Cardiovascular Section, Oklahoma City, Oklahoma. Electronic address: sunil-mathew@ouhsc.edu.
• Heart Rhythm. 2018 Feb 1; 15 (2): 240-247.

BackgroundInappropriate sinus tachycardia (IST) is debilitating despite available treatment. Off-label use of ivabradine for IST prompted this systematic analysis of existing data quality and sample size estimates for adequately powered studies.ObjectiveTo determine clinical efficacy of ivabradine in IST from pooled prospective studies.MethodsAnalysis included ivabradine studies for IST participants without structural heart disease and with follow-up of ≥2 weeks. Heart rate and symptom reduction with ivabradine were estimated based on results of subjective change in symptoms assessed by various data instruments used in each study. Studies were assessed for quality using validated checklists. Sample sizes were calculated based on the magnitude of symptom reduction encountered after treatment with ivabradine.ResultsNine studies met criteria, culminating in 145 patients pooled. Most patients were women (≥70%). Studies were small and not adequately powered, and all reported a decrease in maximum or mean resting heart rate or both, with complete or considerable amelioration of symptoms with ivabradine. Most studies had moderate quality with excellent consistency of study quality and narrow limits of agreement between the quality checklists. Sample size estimates for adequately powered studies with various placebo effects and comparisons with β-blockade are reported.ConclusionsIvabradine effectively reduces heart rate and symptoms in IST, but no study was adequately powered to account for the expected placebo effect on symptoms. A multicenter, randomized, placebo-controlled, active, comparative study with a β-blocker is needed for confirmation. This is especially relevant given the ivabradine's potential teratogenic effect, as many IST patients are females of childbearing potential.Published by Elsevier Inc.

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