Aliskiren
| Evidence Level: L5 | Predicted Indications: 6 |
Table of Contents
- Aliskiren
- Pharmacist Assessment Report
- Aliskiren: From Hypertension to Pulmonary Hypertension with Unclear Multifactorial Mechanism
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- India Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Aliskiren: From Hypertension to Pulmonary Hypertension with Unclear Multifactorial Mechanism
One-Sentence Summary
Aliskiren is a direct renin inhibitor originally used to treat hypertension. The TxGNN model predicts it may be effective for pulmonary hypertension owing to lung disease and/or hypoxia, but no clinical trials and only 4 mostly preclinical publications currently support this direction. Among the seven predicted indications, the most developed evidence is for cerebrovascular disorder (1 terminated Phase 2/3 trial and 12 publications).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension / hypertensive disorder |
| Predicted New Indication | Pulmonary hypertension owing to lung disease and/or hypoxia (rank 2; rank 1 is pulmonary hypertension with unclear multifactorial mechanism) |
| TxGNN Prediction Score | 0.9998 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (2 of 2) – CDSCO approval status is not included in this data |
| Number of Listed Products | 2 (valid: 2) |
| Recommended Decision | Hold |
Note: Rank 1 (pulmonary hypertension with unclear multifactorial mechanism) has no trials or publications (L5). This report focuses on rank 2, which has the more informative evidence, and summarises the other predictions at the end.
Why is This Prediction Reasonable?
Aliskiren is a direct renin inhibitor. It blocks the first, rate-limiting step of the renin-angiotensin-aldosterone system (RAAS), which lowers angiotensin II production. Detailed mechanism of action data is not available in the data compiled for this report, so this description reflects the drug’s known class.
Hypertension and pulmonary hypertension are both vascular pressure disorders, and RAAS activation may contribute to pulmonary vascular remodelling. Animal studies show that intermittent hypoxia drives angiotensin II-mediated effects. Aliskiren reduced hypoxia-induced atrial remodelling in rats (PMID 32982180), and intermittent hypoxia causes sympathoexcitation through circulating angiotensin II (PMID 29645283).
These findings support RAAS involvement in hypoxia-related pathology. However, they come from animal and in vitro models, mostly address atrial remodelling or autonomic effects rather than pulmonary vascular disease, and include no human data. The high TxGNN score is likely driven by overlap with the approved hypertension indication.
Clinical Trial Evidence
Currently no related clinical trials registered for this indication.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32982180 | 2020 | Preclinical (animal) | Drug Des Devel Ther | Investigates aliskiren’s role in atrial remodelling in a chronic intermittent hypoxia rat model |
| 29645283 | 2018 | Preclinical (animal) | J Physiol | Sympathoexcitation after intermittent hypoxia is mediated by circulating angiotensin II; RAS inhibition prevents these effects |
| 39133776 | 2024 | Preclinical (in vitro) | Am J Physiol Regul Integr Comp Physiol | Tests angiotensin release from brain slices; indirect relevance |
| 26502369 | 2016 | Preclinical (mechanistic) | Transplantation | Calcineurin inhibitors upregulate local renal renin and VEGF; indirect relevance |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 189755 | Rasilez 300mg Tablet FC | Strip of 7 Tablet FC | Not specified |
| 187625 | Rasilez 150mg Tablet FC | Strip of 7 Tablet FC | Not specified |
Both licences are valid single-ingredient products from Novartis India Ltd (oral tablets).
Safety Considerations
Safety information from the knowledge graph (not package insert text) lists the following diseases as contraindication-related for aliskiren:
- Angioedema: including hereditary, acquired, and RAAS-blocker-induced forms
- Liver and biliary disease: liver failure, liver disease, hepatic coma/encephalopathy, pancreatitis, gallbladder disease, neonatal jaundice
- Renal and electrolyte disorders: impaired renal function, anuria, renal artery obstruction, potassium deficiency, hypercalcaemia, nephrocalcinosis, phosphorus metabolism disease, hyperparathyroidism, osteitis fibrosa
- Metabolic disorders: diabetes mellitus, diabetic ketoacidosis, gout, hyperuricaemia
- Haematological disorders: neutropenia, agranulocytosis
- Other: hypotensive disorder, systemic lupus erythematosus (including paediatric)
Drug interactions: 114 interactions were identified; those listed are all moderate severity. Examples include:
- Corticosteroids (hydrocortisone, prednisolone, prednisone, dexamethasone, betamethasone, budesonide)
- SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin)
- Potassium supplements (potassium chloride, bicarbonate, citrate, gluconate)
- Aspirin, aprepitant, clarithromycin, clotrimazole, miconazole, eliglustat
Literature from the ALTITUDE trial also raised concerns about combining aliskiren with ACE inhibitors or ARBs in diabetic patients (hypotension, stroke, hyperkalaemia, renal events). Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is very high, but there are no clinical trials and the supporting literature is entirely preclinical and mostly indirect, with no pulmonary vascular data. The prediction is likely driven by overlap with the approved hypertension indication.
Summary of other predicted indications:
| Rank | Predicted Indication | Evidence Level | Decision |
|---|---|---|---|
| 1 | Pulmonary hypertension with unclear multifactorial mechanism | L5 | Hold |
| 3 | Malignant renovascular hypertension | L4 | Hold |
| 4 | Malignant hypertensive renal disease | L5 | Hold |
| 5 | Braddock syndrome | L5 | Hold |
| 6 | Chronic pulmonary heart disease | L4 | Hold |
| 7 | Cerebrovascular disorder | L5 | Research Question |
Cerebrovascular disorder has the strongest support: animal studies show neuroprotection (PMIDs 21124781, 27180190, 21859961), and trial NCT01417104 (ALPINE, Phase 2/3, terminated, 71 participants, surrogate MRI plaque endpoint) tested aliskiren in atherosclerosis. Human evidence for stroke treatment is indirect.
To proceed, the following is needed:
- Mechanism of action data and package insert warnings and contraindications (currently unavailable)
- Preclinical studies in pulmonary vascular models (e.g. hypoxia-induced pulmonary hypertension) to test the RAAS hypothesis directly
- A safety plan addressing the contraindication signals above, especially angioedema, renal impairment, hyperkalaemia, and combination use with ACE inhibitors/ARBs in diabetic patients
- For cerebrovascular disorder: a prospective trial with clinical stroke or cognitive endpoints
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.