Ivabradine
| Evidence Level: L5 | Predicted Indications: 6 |
Table of Contents
Ivabradine: Hypertrichosis (disease)
One-Sentence Summary
Ivabradine is a heart-rate-lowering medicine that inhibits the If (HCN) channel in the sinoatrial node. The TxGNN model’s top-ranked prediction is hypertrichosis, but this has no biological support.
Note: the top-ranked prediction (hypertrichosis, score 0.9979) has no trials, no literature and no plausible mechanism.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication (rank 1) | Hypertrichosis (disease) |
| Best-Supported Candidate | Pulmonary hypertension (rank 7) |
| TxGNN Prediction Score | 0.9979 |
| Evidence Level | L5 for hypertrichosis; L3 for pulmonary hypertension |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold for hypertrichosis; Hold (research question) for pulmonary hypertension |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. From general pharmacology, ivabradine selectively inhibits the If current in sinoatrial pacemaker cells and lowers resting and exercise heart rate without reducing contractility.
Hypertrichosis (rank 1): No plausible link exists. HCN channel inhibition has no known role in hair follicle growth. The score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence. The same applies to the other top-ranked predictions: Ambras syndrome, dental and periodontal malformation syndromes, Dandy-Walker syndromes, hair shaft abnormalities and nephrogenic syndrome of inappropriate antidiuresis. None has trials or literature.
Heart rate reduction may improve right ventricular (RV) function, RV-pulmonary arterial coupling and biventricular interaction, and may reduce RV fibrosis. A caution is that in RV failure, cardiac output can depend on heart rate, so bradycardia is a real concern.
Clinical Trial Evidence
Currently no related clinical trials registered for the predicted indications.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32915674 | 2020 | Preclinical | Am J Respir Cell Mol Biol | Ivabradine heart rate reduction improved RV function and fibrosis in rat PH and RV pressure-loading models |
| 29146614 | 2018 | Preclinical | Am J Physiol Heart Circ Physiol | Heart rate reduction (ivabradine vs carvedilol) improved biventricular function and interactions in monocrotaline-PAH rats |
| 37742537 | 2023 | Cohort | Am J Cardiol | Haemodynamic effects of ivabradine on RV systolic function in COPD with cor pulmonale |
| 24556029 | 2014 | Cohort | J Card Fail | Functional improvement in PAH patients treated with ivabradine |
| 22792738 | 2012 | Cohort | Kardiologiia | In 60 patients with stage III-IV COPD, 2 weeks of ivabradine 10 mg/day was associated with a significant lowering of pulmonary hypertension severity versus controls |
| 32248556 | 2020 | Review | Pharmacotherapy | Scoping review of novel adult uses of ivabradine beyond heart failure and ischaemic heart disease |
| 32946268 | 2020 | Review | Am J Respir Cell Mol Biol | Commentary on heart rate reduction by ivabradine |
| 28701278 | 2017 | Not classified | Eur J Intern Med | Safety and tolerability of ACE inhibitors, ARBs, beta-blockers and ivabradine as supportive therapy in PH |
| 23389056 | 2013 | Not classified | Clin Res Cardiol | Ivabradine in PAH: can it delay the need for parenteral prostanoid therapy? |
| 23021874 | 2012 | Not classified | Eur J Intern Med | Ivabradine in systemic-sclerosis-related PAH |
The remaining retrieved papers are tangential (heart transplant, cirrhotic cardiomyopathy, HFpEF, SHIFT trial co-morbidities and others) and are not listed.
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 10012Y | Coralan | Tablet 5 mg (as hydrochloride) | Not stated in the compiled data |
Safety Considerations
- Drug Interactions: 100 interactions were recorded in total. Examples of those listed in the compiled data:
- Major: aprepitant, clarithromycin, cobicistat, clotrimazole, cisapride, dolasetron, granisetron, levofloxacin, ondansetron, palonosetron, papaverine.
- Moderate: famotidine, ranitidine, cimetidine, nizatidine, dexamethasone, miconazole, metreleptin, troglitazone.
Please refer to the TGA-approved Product Information (PI) for warnings and contraindications, as these were not available in the compiled data.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The top-ranked predictions, including hypertrichosis, are computational artefacts with no mechanistic, clinical or literature support.
- However, no registered trials exist, the evidence is mostly non-randomised, and bradycardia risk in RV failure is a concern.
To proceed, the following is needed:
- The TGA Product Information (approved indications, warnings, contraindications) and detailed mechanism of action data
- Adequately powered, randomised controlled trials in PAH or COPD-associated PH, with RV function and clinical outcomes as endpoints
- A safety and monitoring plan covering bradycardia, RV failure and the major interacting medicines (QT-prolonging drugs and CYP3A4 inhibitors)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.