Inappropriate sinus tachycardia – symptom and heart rate reduction with ivabradine: pooled analysis of prospective studies

Abstract

Objective: Inappropriate sinus tachycardia (IST), is a debilitating condition despite currently available treatment. Ivabradine, a selective sinus node blocker, has been used off-label to treat IST. We therefore systematically reviewed the literature and analyzed the quality of existing data and calculated sample size estimates for adequately powered studies. Methods: We included all available trials, open label prospective studies studies with ivabradine, specifically for IST among subjects with no structural heart disease with a minimum follow-up period of > 2 weeks. Heart rate and symptom reduction with ivabradine were estimated based on results of subjective change in symptoms assessed by data instruments used in the studies. All studies were assessed for quality using two validated checklists scoring the quality of studies. Sample size estimates for future studies were calculated based on the magnitude of symptom reduction encountered after treatment with ivabradine. Results: Nine studies met study criteria, culminating in 145 patients pooled with the majority being women (> 70%). All studies were small, most inadequately powered. All studies reported a decrease in maximum and/or mean resting heart rate with ivabradine. Symptom reduction demonstrated either complete or considerable amelioration. Most studies were at least of moderate quality. Excellent consistency of study quality was gauged by both data-quality tools and narrow limits of agreement between these tools. Calculated sample size estimates for adequately powered studies with a placebo effects of 30 and 50% was 56 and 242 patients respectively. Conclusions: Although ivabradine is effective in reducing heart rate and symptoms in IST patients, none of the studies were adequately powered to account for the expected placebo effect on symptoms. A multicenter-randomized, placebo controlled active comparative study with a beta-blocker is needed to confirm these findings. This is relevant given the ivabradine’s potential teratogenic effect as many IST patients are females of childbearing potential.