Effect of Ivabradine on Heart Rate and Duration of Exercise in Patients With Mild-to-Moderate Mitral Stenosis

Abstract

Background:Symptoms in mitral stenosis (MS) are heart rate (HR) dependent. Increase in HR reduces diastolic filling period with rise in transmitral gradient. By reducing HR, beta-blockers improve hemodynamics and relieve symptoms, but the use may be limited by side effects. The present randomized crossover study looked at comparative efficacy of ivabradine and metoprolol on symptoms, hemodynamics, and exercise parameters in patients with mild-to-moderate MS (mitral valve area, 1–2 cm2) in normal sinus rhythm.Material and Methods:Baseline clinical assessment, treadmill stress testing, and an echocardiographic Doppler evaluation were performed to determine resting HR, total exercise duration, mean gradient across mitral valve, and mean pulmonary artery systolic pressure (PASP). Patients were then allocated to either metoprolol or ivabradine to maximal tolerated doses over 6 weeks (metoprolol: 100 mg twice a day, ivabradine: 10 mg twice a day). Reevaluation was done at the end of this period, and all drugs stopped for washout over 2 weeks. Thereafter, the 2 groups were crossed over to the other drug that was continued for another 6 weeks. Assessment was again performed at the end of this period.Results:Thirty-three patients of 34 completed the protocol. Fifteen were male, mean age was 28.9 ± 6.6 years, all were in New York Heart Association class 2, and mean resting HR was 103.5 ± 7.2/min. Mean mitral valve area was 1.56 ± 0.16 cm2, mean PASP was 38.1 ± 5.1 mm Hg, and mean gradient across mitral valve was 10.6 ± 1.6 mm Hg. Significant decrease in baseline and peak exercise HR was observed at the end of follow-up with both drugs. Reduction in mitral valve gradient after ivabradine (42%) and metoprolol (37%) and reduction in PASP after both ivabradine (23%) and metoprolol (27%) were to a similar extent. Significant reduction in total exercise duration after both ivabradine and metoprolol therapy was observed. One patient developed blurring of vision with ivabradine therapy but did not require discontinuation of drug. An improvement in dyspnea of one grade was observed in all the patients by treatment with both ivabradine and metoprolol.Conclusions:Both metoprolol and ivabradine reduced symptoms and improved hemodynamics significantly from baseline to a similar extent. Ivabradine thus can be used effectively and safely in patients with MS in normal sinus rhythm who are intolerant or contraindicated for beta-blocker therapy.

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

“…This is in contrast to the earlier meta-analysis by Adviento et al [ 20 ], where ivabradine was not significantly different to beta-blocker with regards to these clinical parameters. Individually, the included studies [ 17 - 19 ] showed that ivabradine and beta-blockers were able to similarly improve these outcomes, but in our study, it appears that ivabradine is in fact better. Dhanger [ 21 ] was able to show a statistically significant improvement in exercise duration from baseline among symptomatic MS patients in sinus rhythm, when treated with ivabradine for 3 months.…”

“…The severity of the mitral valve stenosis may play a role. For example, Dhanger [ 21 ] started at a baseline mean gradient of about 12 mm Hg, while Saggu [ 17 ] started at about 10 mm Hg. In both studies, ivabradine and beta-blocker both significantly improved mean gradient, but this slight difference in the hemodynamic severity of the lesions may have spelled the difference to achieving statistical significance between them.…”

“…Agrawal has shown that ivabradine controls exertional symptoms more than metoprolol [ 16 ]. Similarly, Saggu showed that ivabradine was comparable to metoprolol in reducing symptoms and improving hemodynamics in these patients [ 17 ]. Parakh showed that ivabradine is more effective than atenolol in effort-related symptoms [ 18 ], but this was not the same for the study by Rajesh [ 19 ].…”

Beyond Heart Failure and Ischemic Heart Disease: A Scoping Review of Novel Uses of Ivabradine in Adults

“…Seven studies have evaluated the effects of HR reduction with ivabradine in patients with mild to moderate MS and normal sinus rhythm (Table 3). 58–64 In all studies, ivabradine showed a significant reduction in HR from baseline. Two studies showed significant benefits with ivabradine versus β‐blockers on exercise time and working capacity, respectively 58,62 .…”

Ivabradine in Cardiovascular Disease

“…In this issue of the Journal, Saggu et al 29 present data from a study that was designed to evaluate the cardiovascular effects of ivabradine as compared with metoprolol in patients with mild to moderate mitral stenosis. Although the study population was small, the results are more informative than the much larger multicenter studies because by using a crossover design and by titrating the doses of both ivabradine and metoprolol to a heart rate end point, the investigators eliminated the bias that occurred in the large trials because ivabradine was titrated to heart rate in the treatment group but the dose of the β-blocker was not titrated in the placebo group.…”