From the Guidelines
Ivabradine works by selectively inhibiting the "I-funny" or "If" channel in the sinoatrial node of the heart, which is responsible for normal automaticity of the sinus node, thereby reducing the sinus node pacemaker activity and slowing the heart rate. This mechanism of action is supported by the 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia, as reported in the Journal of the American College of Cardiology 1. The guideline states that ivabradine is an inhibitor of the "I-funny" or "If" channel, which results in slowing of the heart rate.
Some key points about ivabradine's mechanism of action include:
- Ivabradine reduces the slope of the diastolic depolarization phase of the cardiac action potential, leading to a decrease in heart rate 1
- Unlike beta-blockers or calcium channel blockers, ivabradine does not affect myocardial contractility, blood pressure, or intracardiac conduction 1
- The drug is typically dosed at 5-7.5 mg twice daily, with the dose adjusted based on heart rate response 1
- Ivabradine is primarily used to treat chronic heart failure and stable angina in patients who cannot tolerate beta-blockers or when beta-blockers alone are insufficient 1
The heart rate reduction provided by ivabradine decreases myocardial oxygen demand while increasing diastolic filling time, which improves coronary perfusion and cardiac efficiency. As reported in the BEAUTIFUL and SHIFT trials, ivabradine resulted in additional heart rate reductions of 6 to 8 bpm and proved to be generally safe 1. Overall, ivabradine's unique mechanism of action makes it a valuable treatment option for patients with certain cardiovascular conditions, as supported by the guideline recommendations 1.
From the FDA Drug Label
Ivabradine blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker I fcurrent, which regulates heart rate. 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.
The mechanism of action of ivabradine is to block the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel, which is responsible for the cardiac pacemaker I f current. This results in a reduction of the spontaneous pacemaker activity of the cardiac sinus node, leading to a decrease in heart rate. Ivabradine has no effect on ventricular repolarization and no effects on myocardial contractility 2, 2, 2.
- Key points:
- Blocks HCN channel
- Reduces spontaneous pacemaker activity of the cardiac sinus node
- Decreases heart rate
- No effect on ventricular repolarization
- No effects on myocardial contractility
From the Research
Mechanism of Action of Ivabradine
The mechanism of action of ivabradine is based on its ability to inhibit the funny current (If) in the sinoatrial node, which is the main determinant of the pacemaker function of the sinus node 3, 4, 5. This inhibition leads to a reduction in heart rate without affecting myocardial contractility or vascular tone 4, 5. Ivabradine is a use-dependent inhibitor that targets the sinoatrial node, making it a unique agent distinct from beta-blockers and calcium channel blockers 5.
Key Effects of Ivabradine
- Reduces heart rate by inhibiting the funny current (If) in the sinoatrial node 3, 4, 5
- Does not affect myocardial contractility or vascular tone 4, 5
- Approved for use in heart failure with reduced ejection fraction to reduce heart failure readmissions 3, 5
- May be effective in treating inappropriate sinus tachycardia, especially in patients who cannot tolerate beta-blockers or calcium channel blockers 6, 7
Clinical Applications of Ivabradine
Ivabradine has been shown to be effective in various clinical applications, including: