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

Background: Symptoms of mitral stenosis (MS) are worsened during tachycardia and exercise. Beta-blockers are used in controlling heart rate (HR) in MS, resulting in symptom improvement, but coming with significant side effects. Ivabradine has a selective action on the sinus node devoid of the usual side effects of beta-blockers. Small studies have recently investigated the role of ivabradine in MS in sinus rhythm. Our aim was to determine the efficacy of ivabradine, compared to beta-blockers, 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 using MEDLINE, Google Scholar, ScienceDirect, Scopus, Clinical Key, Cochrane, and clinicaltrials.gov databases in all languages and examined reference lists of studies. We included studies if they are: 1) randomized controlled trials comparing ivabradine and beta-blockers; 2) of adults >= 19 years old with MS in sinus rhythm; and 3) reported data on exercise duration, maximum HR achieved, resting HR, mean gradient, and working capacity. Studies identified 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 difference, carried out using Review Manager (RevMan) 5.3. Results: Pooled analysis from five identified trials showed that among patients with MS in sinus rhythm, ivabradine was better compared to beta-blockers in total exercise duration (mean difference: 32.73 s (95% CI: 12.19, 53.27; P = 0.002; I-2 = 0%)), maximum HR achieved after exercise (mean difference: -3.87 beats per minute (95% CI: -5.88, -1.860; P = 0.0002; I-2 = 23%)), and work capacity (mean difference: 0.56 METS (95% CI: 0.33, 0.80; P < 0.00001; I-2 = 0%)); inferior to beta-blockers in resting HR achieved (mean difference: 1.83 s (95% CI: 0.39, 3.28; P = 0.01; I-2 = 91%)); and comparable to beta-blockers in terms of mean gradient (mean difference: -0.52 mm Hg (95% CI: -1.20, 0.16; P = 0.13; I-2 = 6%)). Conclusions: Ivabradine is better or comparable to beta-blockers in terms of the outcomes measured, and may be considered as an alternative for patients with MS in sinus rhythm who are intolerant to beta-blockers.