What is Ivabradine?
Ivabradine is a selective sinus node inhibitor used to lower heart rate in patients with chronic heart failure and angina.
It acts on the If (funny) channels in the sinoatrial (SA) node of the heart — slowing down the pacemaker activity and thus reducing the heart rate.
- Drug class: If (funny) channel blocker
- Brand name: Corlanor (U.S.), Procoralan (Europe)
- Approved by: U.S. FDA in 2015 for heart failure
Mechanism of Action
Unlike beta-blockers or calcium channel blockers, It does not affect myocardial contractility or blood pressure.
It selectively inhibits the If channels in the SA node, which controls the pacemaker activity of the heart.
Step-by-step action:
- Inhibits If current in the SA node.
- Slows spontaneous diastolic depolarization.
- Reduces heart rate (negative chronotropy).
- Improves myocardial oxygen supply-demand balance.
Result: Lower heart rate → improved cardiac efficiency → reduced symptoms and hospitalizations in heart failure.
Therapeutic Uses
| Condition | Purpose |
|---|---|
| Chronic Heart Failure (HFrEF) | Reduces heart rate and mortality (used when HR >70 bpm despite beta-blockers) |
| Stable Angina Pectoris | Reduces frequency of angina attacks when beta-blockers are contraindicated |
| Inappropriate Sinus Tachycardia (off-label) | Controls elevated sinus heart rate |
Guideline Note:
According to the European Society of Cardiology (ESC), It is recommended in HFrEF patients (EF ≤35%) who remain symptomatic despite optimal therapy and have a resting heart rate ≥70 bpm.
Dosage & Administration
| Formulation | Dose |
|---|---|
| Starting Dose | 5 mg twice daily (with meals) |
| Maintenance Dose | 5–7.5 mg twice daily |
| Elderly Patients | 2.5–5 mg twice daily (depending on tolerance) |
Note: Adjust dose every 2 weeks based on resting heart rate and tolerance.
Side Effects
| Common Side Effects | Rare/Serious Side Effects |
|---|---|
| Bradycardia (slow HR) | Atrial fibrillation |
| Visual disturbances (phosphenes – brightness) | AV block |
| Dizziness | Hypotension |
| Headache | Syncope (fainting) |
Visual effects are due to Its action on retinal Ih channels — usually mild and transient.
Contraindications
- Resting heart rate <60 bpm
- Sick sinus syndrome, SA block
- Severe hepatic impairment
- Acute decompensated heart failure
- Pregnancy and lactation
- Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin)
Drug Interactions
| Drug Type | Effect |
|---|---|
| CYP3A4 inhibitors (e.g., Verapamil, Diltiazem) | ↑ levels → risk of bradycardia |
| QT-prolonging drugs | Additive cardiac effects |
| Strong inducers (e.g., Rifampicin, Phenytoin) | ↓ Ivabradine effectiveness |
Clinical Benefits
- Reduces hospitalizations in heart failure patients
- Improves exercise tolerance and quality of life
- Safe for patients intolerant to beta-blockers
- No major effect on blood pressure or myocardial contractility
Clinical Evidence
The SHIFT trial (Systolic Heart Failure Treatment with the If Inhibitor Trial) showed:
- 18% reduction in primary endpoint (CV death or HF hospitalization)
- 26% reduction in hospitalizations for worsening HF
1.Discovery Origin
Ivabradine was discovered by Servier Laboratories (France) in the early 1990s during research for non–beta-blocking heart rate–lowering agents.
It was the first drug ever designed to target the “funny” current (If current) in the heart’s sinoatrial node — a novel concept at the time.
Reference: Servier Research History – Cardiovascular Innovations
2. Ivabradine Doesn’t Affect Cardiac Contractility or Blood Pressure
Unlike beta-blockers or calcium channel blockers, Ivabradine reduces heart rate without decreasing contractility, cardiac output, or arterial pressure.
This makes it ideal for patients who can’t tolerate beta-blockers due to low blood pressure or asthma.
This selective effect is called “pure heart rate reduction.”
3. Ivabradine Can Cause “Phosphenes” (Visual Brightness Phenomenon)
A rare but fascinating effect of Ivabradine is phosphenes — brief moments of enhanced brightness or visual flashes, especially in dim light.
This happens because Ivabradine blocks similar Ih channels in retinal photoreceptors, affecting light signal processing.
Usually, it’s mild and disappears with continued use.
Fun fact: Up to 15% of patients in trials reported this phenomenon!
4. Ivabradine Works Only in Normal Sinus Rhythm
Ivabradine’s mechanism depends on sinus node activity.
Therefore, it’s ineffective in patients with atrial fibrillation, flutter, or pacemaker rhythms, since these don’t rely on the SA node’s If current.
This unique feature makes it highly rhythm-selective.
5. “SHIFT” Trial – A Game-Changing Study
The SHIFT Trial (Systolic Heart Failure Treatment with If Inhibitor Ivabradine Trial) was a landmark 2010 study published in The Lancet.
It proved Ivabradine significantly:
- Reduced hospitalization by 26%
- Improved survival in patients with HR ≥70 bpm
- Worked best when combined with beta-blockers
Source: The Lancet – SHIFT Trial Summary
6. Ivabradine is Metabolized by CYP3A4 Enzyme
Ivabradine undergoes hepatic metabolism via CYP3A4, producing an active metabolite (N-desmethyl Ivabradine).
Hence, drug interactions with CYP3A4 inhibitors (like ketoconazole, verapamil) can dangerously increase plasma levels and cause severe bradycardia.
This pharmacokinetic detail makes liver health monitoring essential during long-term therapy.
7. Ivabradine Improves Coronary Perfusion
By slowing heart rate, Ivabradine lengthens diastole, allowing better coronary artery filling and oxygen supply to the myocardium — especially beneficial in angina pectoris.
Unique Advantage:
Even though it slows HR, it doesn’t reduce stroke volume → thus maintaining cardiac output.
8. Emerging Research:
Recent studies show Ivabradine may help in non-traditional cardiovascular conditions, including:
| Condition | Research Insight |
|---|---|
| Postural Orthostatic Tachycardia Syndrome (POTS) | Helps reduce tachycardia & palpitations |
| Hyperadrenergic States | Controls excessive heart rate from stress or thyroid disease |
| Chemotherapy-induced Tachycardia | Experimental benefit under investigation |
| Sepsis-induced Tachycardia | Shows promise in reducing HR without affecting BP |
Clinical Trials Reference: ClinicalTrials.gov – Ivabradine Studies
9. Ivabradine May Improve Exercise Tolerance and Quality of Life
By slowing the HR and reducing myocardial oxygen demand, Ivabradine helps patients exercise longer with less fatigue and breathlessness — an outcome strongly supported by patient surveys in SHIFT and BEAUTIFUL trials.
Result: Patients report better endurance and reduced symptoms after 2–3 months.
10. Veterinary & Research Use
Surprisingly, Ivabradine is being tested in veterinary cardiology (especially dogs with dilated cardiomyopathy) for controlled HR reduction without depressing contractility.
Source: Journal of Veterinary Cardiology, 2023 –
What is Ivabradine used for?
It is primarily used to treat chronic heart failure and stable angina pectoris. It helps lower the heart rate in patients whose heartbeat is too fast, improving blood flow and reducing strain on the heart.