Enalapril
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Enalapril: From Hypertension and Heart Failure to Chronic Pulmonary Heart Disease
One-Sentence Summary
Enalapril is an ACE inhibitor originally used to treat hypertension and congestive heart failure. The TxGNN model predicts it may be effective for chronic pulmonary heart disease (cor pulmonale). Evidence is limited: 0 registered clinical trials and 20 retrieved publications, of which only a handful address this condition directly (mostly small, older clinical studies and one animal study).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension; congestive heart failure (the Singapore licence records contain no indication text, so these come from the TxGNN knowledge graph) |
| Predicted New Indication | Chronic pulmonary heart disease |
| TxGNN Prediction Score | 98.91% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 18 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the compiled data. Based on known pharmacology, enalapril is an ACE inhibitor. Its efficacy in hypertension and heart failure is established, and it may be mechanistically applicable to chronic pulmonary heart disease.
Blocking the renin-angiotensin system lowers angiotensin II-mediated vasoconstriction and afterload. It may also reduce right ventricular hypertrophy and fibrosis. In a rat study, enalapril reduced ventricular collagen in animals recovering from chronic hypoxia, which supports a biological rationale for the right heart.
The clinical link is weaker. Chronic pulmonary heart disease is right-sided heart disease, usually secondary to lung disease. Most of the retrieved literature concerns left-sided heart failure, which is indirect evidence. Only a few small, older human studies look at cor pulmonale itself.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 1405196 | 1992 | Small clinical study (11 patients) | Kardiologia Polska | Enalapril 10–20 mg/day added to standard therapy in cor pulmonale from COPD; the title reports improved haemodynamics and exercise tolerance |
| 9282581 | 1996 | Comparative clinical study (30 patients) | J Assoc Physicians India | Enalapril plus conventional treatment vs conventional treatment alone in chronic cor pulmonale; right ventricular dimensions and renal profile assessed over 6 weeks |
| 3032121 | 1986 | Clinical study (16 patients) | Arch Inst Cardiol Mex | Enalapril ~20 mg/day in pulmonary arterial hypertension (primary and secondary), with catheterisation before and after treatment |
| 9140694 | 1997 | Preclinical (rat) | Cardiovasc Drugs Ther | Enalapril and regression of hypoxia-induced pulmonary hypertension, right ventricular hypertrophy and fibrosis |
| 40329926 | 2025 | Review | High Alt Med Biol | Review of management of chronic mountain sickness, a hypoxia-related condition that can involve pulmonary hypertension |
| 9642838 | 1998 | Clinical study (20 patients) | Ann Ital Med Int | Long-term ACE inhibition and pulmonary diffusion and ventilation-perfusion in chronic heart failure; indirect (left heart) |
| 6313787 | 1983 | Haemodynamic study (15 patients) | J Am Coll Cardiol | Enalapril raised cardiac index and lowered pulmonary capillary wedge and right atrial pressures in chronic heart failure; indirect |
| 6100603 | 1983 | Haemodynamic study (12 patients) | J Hypertens Suppl | Sustained haemodynamic effects of enalapril in left ventricular failure, including pulmonary arterial pressure; indirect |
| 2210899 | 1990 | Small clinical study (5 patients) | Int J Cardiol | Enalapril as initial and sole treatment in severe chronic heart failure with sodium retention; indirect |
| 39210725 | 2024 | RCT post hoc analysis | JAMA Cardiol | Sacubitril/valsartan and all-cause hospitalisation in heart failure (PARADIGM-HF/PARAGON-HF); indirect (enalapril is the comparator) |
No randomised controlled trial in chronic pulmonary heart disease was found. The remaining retrieved papers are unrelated or only loosely related (for example, general heart failure management and a nebivolol review).
Singapore Market Information
Enalapril has 18 valid single-ingredient licences, all oral tablets and none cancelled. The licence records contain no approved-indication text. The table lists five of them.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| SIN07658P | KORANDIL 10 TABLET 10 mg | Tablet | Remedica Ltd |
| SIN11572P | ENAPRIL-5 TABLET 5 mg | Tablet | Intas Pharmaceuticals Ltd |
| SIN11371P | ENAP TABLET 10 mg | Tablet | Krka d.d. Novo Mesto |
| SIN08232P | APO-ENALAPRIL TABLET 5 mg | Tablet | Apotex Inc |
| SIN09293P | ECARIL TABLET 10 mg | Tablet | Shin Poong Pharmaceutical Co Ltd |
Safety Considerations
- Contraindication signals (knowledge-graph data): angioedema in all forms, including acquired, hereditary, non-histaminic and RAAS-blocker-induced angioedema.
- Drug Interactions: 100 interactions were recorded; the 20 reviewed include two Major ones.
- Major: potassium citrate and potassium bicarbonate (hyperkalaemia risk).
- Moderate: corticosteroids (hydrocortisone, dexamethasone, betamethasone, budesonide, triamcinolone), antidiabetic agents (metformin, alogliptin, linagliptin, canagliflozin, dapagliflozin, empagliflozin, chlorpropamide), acetylsalicylic acid, morphine, bupropion, dronabinol, picosulfuric acid and polyethylene glycol with electrolytes.
- Indication-specific concerns: ACE inhibitors can cause hypotension and acute renal function decline when renal perfusion is compromised. This matters if used in acute right heart strain or in patients with renal impairment.
Please refer to the package insert for the complete warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The high TxGNN score (98.91%) is supported only by small, older studies in cor pulmonale, one animal study, and indirect left heart failure data. There are no registered trials and no RCTs. The case for further investigation is plausible but not yet strong.
To proceed, the following is needed:
- Mechanism of action data and a clearer mechanistic link to right ventricular and pulmonary vascular disease
- A critical appraisal of the small cor pulmonale studies (PMID 1405196, 9282581, 3032121), including full-text review of their outcomes
- A well-designed randomised trial in chronic pulmonary heart disease, for example in cor pulmonale from COPD, with right ventricular function and exercise tolerance as endpoints
- The package insert warnings and contraindications for Singapore-registered products
- A safety plan covering hypotension, renal function, potassium and angioedema
For context, among the other predicted indications, chronic kidney disease has the strongest supporting evidence (meta-analyses and several trials). However, ACE inhibitor renoprotection there is already established practice rather than a novel repurposing signal.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.