Ivabradine Versus Beta-blockers in Mitral Stenosis in Sinus Rhythm: An Updated Meta-analysis of Randomized Controlled Trials

Abstract

Background: Symptoms of mitral stenosis (MS) are worsened during tachycardia and exercise. Beta-blockers (BB) are used in controlling heart rate (HR) in MS to relieve symptoms, but can cause significant side effects. Ivabradine has a selective action on the sinus node and is devoid of the usual side effects of BB. Only small studies have investigated the role of ivabradine in MS in sinus rhythm. Objectives: To compare the efficacy of ivabradine with BB in terms of exercise duration, maximum HR achieved, resting HR, mean gradient and working capacity among patients with MS in sinus rhythm Methods: We conducted a systematic search of studies in all languages using MEDLINE, Google Scholar, ScienceDirect, Scopus, Clinical Key, Cochrane and clinicaltrials.gov databases and review of reference lists of studies. We included randomized controlled trials that compared ivabradine and BB in adults with MS in sinus rhythm and reported data on exercise duration, maximum HR achieved, resting HR, mean gradient or working capacity. Identified studies were assessed for risk of bias using the Cochrane Collaboration Tool for Assessing Risk of Bias. We used inverse variance analysis of fixed effects to compute for mean differences, carried out using Review Manager 5.3. Results: Pooled analysis from five identified trials showed that among patients with MS in sinus rhythm, ivabradine was better than BB in increasing total exercise duration (mean difference of 32.73 s [95% CI 12.19, 53.27; p=0.002; I2=0%]), reducing maximum HR achieved after exercise (mean difference -3.87 beats per minutes [95% CI -5.88, -1.860; p=0.0002; I2=23%]) and improving work capacity (mean difference of 0.56 metabolic equivalents [95% CI 0.33, 0.80; p<0.00001; I2=0%]). Ivabradine was inferior to BB in resting HR achieved (mean difference of 1.83 s [95% CI 0.39, 3.28; p=0.01; I2=91%]); and similar to BB in terms of mean blood pressure gradient (mean difference of -0.52 mmHg [95% CI -1.20, 0.16; p=0.13; I2=6%]). Conclusion: Ivabradine was better or at least similar to BB in most outcomes measured and may be considered as an alternative treatment for patients with MS in sinus rhythm who are intolerant to BB. Keywords: ivabradine, mitral stenosis.