Resident Physician Penn State Hershey Medical Center HUMMELSTOWN, Pennsylvania
Introduction: Ivabradine has emerged as a new therapy for patients who have heart failure with reduced ejection fraction (EF). While its efficacy regarding reduction of cardiovascular events has been shown, less is known about its safety profile. Ivabradine is a selective inhibitor of If channels in the sinoatrial node resulting in reduced heart rate. New guideline now recommends (class IIa) starting ivabradine on patients with an EF less than 35% who are on a maximally tolerated beta-blocker but with a heart rate over 70 beats per minute.
Method: A meta-analysis was performed using randomized controlled trials (RCTs) testing ivabradine compared to placebo. The primary analysis calculated the odds ratio (OR) and 95% confidence intervals (CI) of bradycardia, new-onset atrial fibrillation, visual disturbances, and hypertension. A secondary analysis tested each outcome for heterogeneity of treatment effect (HTE) using Chi2 and I2 tests between shorter versus longer follow-up durations and preserved EF versus reduced EF.
Results: Five RCTs were identified comparing ivabradine to placebo, which included a total of 37,549 participants. There was an increased risk of bradycardia [OR 5.52, 95% CI 3.41-8.95], atrial fibrillation [OR 1.24, 95%CI 1.06-1.44], visual disturbances [OR 5.03, 95%CI 3.45-7.33], and hypertension [OR 1.21, 95%CI 1.12-1.30] with ivabradine compared to placebo. When performing the test for subgroup differences, there was significant HTE between shorter and longer follow up durations for atrial fibrillation [Chi2=5.18, p=0.02, I2=80.7%]. When performing the test for subgroup differences between patients with preserved EF and reduced EF, there was no significant HTE for any of the endpoints.
Conclusion: Ivabradine was associated with an increased risk of bradycardia, atrial fibrillation, visual disturbances, and hypertension. In addition, longer follow up was associated with an increased incidence of atrial fibrillation compared to shorter follow up times. Ejection fraction (preserved and reduced) did not affect adverse events.