Ramipril
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Ramipril: From Hypertension to Pulmonary Hypertension (Unclear Multifactorial Mechanism)
One-Sentence Summary
Ramipril is an ACE inhibitor marketed in South Africa as several oral products (the records supplied do not state an approved indication). The TxGNN model ranks pulmonary hypertension with unclear multifactorial mechanism as its top prediction, but no clinical trials and no relevant publications support this specific prediction. The strongest evidence in this pack is for a different, lower-ranked candidate, cerebral artery occlusion, and it is still only indirect (1 Phase 2 trial, mostly rodent data).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the supplied SAHPRA records (ramipril is generally used for hypertension and cardiovascular risk reduction) |
| Predicted New Indication | Pulmonary hypertension with unclear multifactorial mechanism |
| TxGNN Prediction Score | 99.93% |
| Evidence Level | L5 (model prediction only) |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 7 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the supplied pack. Ramipril is an angiotensin-converting enzyme (ACE) inhibitor, and ACE inhibition could plausibly affect vascular remodelling. That is the only mechanistic link offered for the lead prediction.
The label “pulmonary hypertension with unclear multifactorial mechanism” is non-specific, so the mechanistic argument is weak. The 20 papers retrieved for the related prediction, “pulmonary hypertension owing to lung disease and/or hypoxia”, are about hypoxia biology in neurological disease, cancer and fibrosis. None involve ramipril or pulmonary hypertension, so they look like keyword matches rather than drug-specific evidence.
The other nine predictions are also model-only, apart from the one below:
| Predicted indication | TxGNN score | Evidence level | Note |
|---|---|---|---|
| Pulmonary hypertension, hypoxia/lung disease | 99.93% | L5 | Off-topic literature only |
| Malignant renovascular hypertension | 99.93% | L5 | Renin-angiotensin system link is plausible, but ACE inhibitors carry a known renal risk in renovascular disease |
| Malignant hypertensive renal disease | 99.93% | L5 | RAAS blockade is mechanistically relevant; no evidence supplied |
| Braddock syndrome | 99.91% | L5 | No plausible link evident |
| Brain stem infarction | 99.89% | L5 | Possible cerebrovascular protection; no direct evidence |
| Prinzmetal angina | 99.83% | L5 | One unrelated genetic association paper |
| Intracerebral haemorrhage | 99.82% | L4 | Rodent data only |
| ABri amyloidosis | 99.79% | L5 | No plausible link evident |
| Cerebral artery occlusion | 99.74% | L4 | Strongest signal, but still indirect |
Clinical Trial Evidence
For the lead prediction (pulmonary hypertension), currently no related clinical trials are registered.
The only trial in the pack relates to the lower-ranked cerebral artery occlusion candidate:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00005928 | Phase 2 | Completed | 25 | Effect of ramipril on vascular inflammation and arterial stiffness (2000–2002). Its endpoints are vascular surrogates, and it did not study cerebral artery occlusion or stroke directly (relevance grade C). |
Literature Evidence
For the lead prediction, currently no relevant literature is available. The 20 hypoxia-related papers retrieved for the related pulmonary hypertension candidate do not involve ramipril and are not listed.
The publications below relate to the lower-ranked cerebral artery occlusion and intracerebral haemorrhage candidates:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 8797135 | 1996 | Randomised, single-blind, placebo-controlled human study | J Cardiovasc Pharmacol | Ramipril vs enalapril effects on regional cerebral blood flow in 15 elderly hypertensive patients with carotid stenosis |
| 21901125 | 2011 | Preclinical/Review | PLoS One | Telmisartan, ramipril and their combination in rat stroke prevention and acute ischaemia models |
| 20407464 | 2010 | Preclinical | J Cereb Blood Flow Metab | ACE inhibition reduced infarct size in normotensive but not hypertensive rats |
| 18300867 | 2008 | Preclinical | J Hypertens | Candesartan, but not ramipril, pretreatment improved stroke outcome in rats |
| 16272888 | 2005 | Preclinical | Neuroreport | Ramipril and candesartan both reduced infarct volume in hypertensive rats after middle cerebral artery occlusion |
| 15834293 | 2005 | Preclinical | J Hypertens | Telmisartan vs ramipril effects on cerebrovascular structure in hypertensive rats |
| 15721222 | 2005 | Preclinical | Neurosci Lett | Ramipril reduced brain plasminogen/MMP activity in stroke-prone hypertensive rats |
| 35098999 | 2022 | Preclinical (zebrafish screen) | Dis Model Mech | Drug screen for neuroprotection after intracerebral haemorrhage |
South Africa Market Information
Ramipril has 7 SAHPRA registrations; the 5 below were supplied. The records supplied do not include approved indication text or manufacturer.
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. W/7.1.3/232 | Ramiwin 1.25 Mg | Capsule | Not provided |
| Reg. No. A39/7.1.3/0242 | Austell-ramipril | Capsule | Not provided |
| Reg. No. A39/7.1.3/0239 | Austell-Ramipril 1.25Mg | Capsule | Not provided |
| Reg. No. 31/7.1/0677 | Tri-plen 2.5mg/2.5mg | Tablet | Not provided |
| Reg. No. 44/7.1/0612 | Co Ramiwin 2.5/12.5 Mg | Tablet | Not provided |
All products are oral (capsule or tablet).
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
One point from the prediction notes: ACE inhibitors are known to carry renal risk in renovascular disease (for example, bilateral renal artery stenosis). This needs careful review before any use in the renovascular hypertension candidates.
Conclusion and Next Steps
Decision: Hold
Rationale: The lead prediction is supported only by a model score (99.93%), with no trials and no relevant literature, and the disease label is non-specific. Ramipril is widely marketed in South Africa, but there is no evidence to justify pursuing this indication now.
To proceed, the following is needed:
- SAHPRA package insert warnings and contraindications (a blocking gap for any safety screening).
- Mechanism of action data, for example from DrugBank.
- A more specific pulmonary hypertension classification, then a targeted search for ramipril-specific human evidence.
- If a fallback candidate is wanted, cerebral artery occlusion is the best-supported (L4). It would need a ramipril-specific clinical trial with stroke outcomes, since the current data are surrogate endpoints and rodent studies, some of which involved other agents or showed blood pressure–dependent effects.
This report is for research reference only and does not constitute medical advice. Predicted candidates require clinical validation before any application.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.