From the Guidelines
Ivabradine is recommended for patients with symptomatic stable chronic heart failure with reduced ejection fraction (HFrEF) who are receiving guideline-directed medical therapy, including a beta blocker at maximum tolerated dose, and have a heart rate of 70 bpm or greater at rest. This is based on the 2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure, which suggests that ivabradine can be beneficial in reducing heart failure hospitalization for these patients 1.
Mechanism of Action
Ivabradine works by selectively inhibiting the If current in the sinoatrial node, providing heart rate reduction without affecting blood pressure, myocardial contractility, or cardiac conduction. This unique mechanism of action makes it a valuable treatment option for patients who cannot tolerate traditional heart rate-lowering medications like beta-blockers or require additional heart rate control.
Clinical Uses
The primary use of ivabradine is to reduce the risk of heart failure hospitalization in patients with symptomatic stable chronic HFrEF, as evidenced by a reduction in the composite endpoint of cardiovascular death or heart failure hospitalization in clinical trials 1. It is particularly beneficial for patients with a left ventricular ejection fraction (LVEF) ≤35%, in sinus rhythm with a resting heart rate of ≥70 bpm, and who have been hospitalized for heart failure in the preceding 12 months.
Key Considerations
- Ivabradine should only be considered after patients have been optimized on guideline-directed medical therapy, including beta-blockers at maximum tolerated doses.
- The initiation of ivabradine requires careful patient selection, including those with a resting heart rate of 70 bpm or greater, to maximize its benefits.
- Monitoring and adjustment of the ivabradine dose may be necessary to achieve the desired heart rate reduction while minimizing potential side effects.
Side Effects and Contraindications
While the provided evidence does not extensively detail side effects and contraindications, it is crucial to consider these factors in clinical practice. Common side effects include phosphenes (visual disturbances), and ivabradine is contraindicated in patients with severe hepatic impairment, resting heart rate below 60 bpm, and those dependent on pacemakers, based on general knowledge of the medication.
From the FDA Drug Label
Ivabradine is a hyperpolarization-activated cyclic nucleotide-gated channel blocker that reduces the spontaneous pacemaker activity of the cardiac sinus node by selectively inhibiting the I fcurrent, resulting in heart rate reduction with no effect on ventricular repolarization and no effects on myocardial contractility. Ivabradine blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker I fcurrent, which regulates heart rate. Ivabradine is indicated: • To reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with reduced left ventricular ejection fraction.
The uses of Ivabradine include reducing the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with reduced left ventricular ejection fraction 2. The mechanism of action of Ivabradine involves blocking the hyperpolarization-activated cyclic nucleotide-gated channel, which reduces the spontaneous pacemaker activity of the cardiac sinus node, resulting in heart rate reduction with no effect on ventricular repolarization and no effects on myocardial contractility 2. Key points about Ivabradine's mechanism of action include:
- Selective inhibition of the I f current
- Reduction of heart rate with no effect on ventricular repolarization
- No effects on myocardial contractility Ivabradine's clinical use is based on its ability to reduce heart rate, which is dependent on the baseline heart rate, with greater heart rate reduction occurring in patients with higher baseline heart rate 2.
From the Research
Mechanism of Action
- Ivabradine is a unique agent that reduces heart rate without affecting myocardial contractility or vascular tone 3
- It is a use-dependent inhibitor targeting the sinoatrial node, selectively inhibiting I f current in pacemaker cells 4
- Ivabradine's mechanism of action is distinct from beta-blockers and calcium channel blockers 3
Uses
- Approved for use in the United States as an adjunct therapy for heart rate reduction in patients with heart failure with reduced ejection fraction 3
- Used in the treatment of patients with inappropriate sinus tachycardia, who often cannot tolerate beta-blockers and/or calcium channel blockers 3, 4
- Ivabradine may also be used in stable ischemic heart disease, although evidence is conflicting regarding efficacy in symptom reduction and mortality benefit 3
- Off-label uses include premedication for coronary computed tomography angiography, heart rate lowering in postural tachycardia syndrome (POTS), and inappropriate sinus tachycardia 4
Clinical Outcomes
- Ivabradine has demonstrated improved clinical outcomes due to reduction in heart failure readmissions 3
- In patients with heart failure with reduced ejection fraction, ivabradine has been shown to improve symptoms, quality of life, and global assessment 5
- Ivabradine has also been shown to reduce the combined endpoint of cardiovascular death and hospitalization for heart failure 5
- A significant reduction in left ventricular dimensions has been observed in patients treated with ivabradine 5