Ramipril

證據等級: L5

預測適應症: 10 個

Ramipril: From Hypertension/RAAS Therapy to Pulmonary Hypertension Owing to Lung Disease and/or Hypoxia

One-Sentence Summary

Ramipril is an angiotensin-converting enzyme (ACE) inhibitor that suppresses the renin-angiotensin-aldosterone system (RAAS); its original approved indication is not recorded in this evidence pack. The TxGNN model predicts it may be effective for Pulmonary Hypertension Owing to Lung Disease and/or Hypoxia, but currently 0 clinical trials and 20 publications support this direction — and none of the 20 publications actually studies ramipril or ACE inhibitors in pulmonary hypertension.

Quick Overview

Item	Content
Original Indication	Not available in this evidence pack (no `original_indications` or `licenses` records; flagged as data gap DG001)
Predicted New Indication	Pulmonary Hypertension Owing to Lung Disease and/or Hypoxia
TxGNN Prediction Score	99.93%
Evidence Level	L5 (model prediction only)
US Market Status	Not Marketed
Number of NDAs	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism-of-action data from DrugBank is not available for this candidate (flagged as data gap DG002, High severity). However, information embedded in this evidence pack’s own trial and literature records confirms ramipril’s pharmacological class: it is referenced as an ACE inhibitor (see clinical trial NCT00005928, “Angiotensin Converting Enzyme Inhibitor Therapy… trade name Ramipril”) that acts by suppressing the RAAS pathway.

The mechanistic hypothesis for pulmonary hypertension is that RAAS inhibition could theoretically reduce hypoxia-induced pulmonary vascular remodeling, since angiotensin II contributes to vascular smooth muscle proliferation and fibrosis under chronic hypoxic stress. This is a plausible, but currently unproven, extension of ramipril’s known cardiovascular pharmacology.

Critically, all 20 literature records retrieved for this indication are basic hypoxia biology papers — covering topics such as brain aging, cognitive impairment, tumor hypoxia signaling, and altitude physiology — none of which mention ramipril or ACE inhibitors, and none study pulmonary hypertension treatment directly. The mechanistic link therefore remains theoretical, not evidence-based.

Clinical Trial Evidence

Currently no related clinical trials registered for this indication.

Literature Evidence

Note: The 20 retrieved publications are general hypoxia-biology background literature and do not directly study ramipril, ACE inhibitors, or pulmonary hypertension treatment. They are listed below for transparency but do not constitute drug-specific evidence.

PMID	Year	Type	Journal	Key Findings
33862277	2021	Review	Ageing Research Reviews	Hypoxia’s role in brain aging and neurodegeneration (general biology, not drug-specific)
34618295	2022	Review	Metabolic Brain Disease	Clinical and molecular mechanisms of hypoxia-induced cognitive impairment
37328448	2023	Basic Research	Advanced Science	Hypoxia tolerance via NAT10/SEPT9/HIF-1α feedback loop in gastric cancer
21328446	2011	Review	J Cellular Biochemistry	General review of hypoxia-mediated cellular and organismal responses
31706510	2019	Basic Research	Trends in Cancer	Deubiquitinases regulate HIF stability in hypoxic tumor environments
11172576	2000	Review	Respiratory Care Clinics of North America	Review of the physiological mechanisms of hypoxemia
34535359	2021	Review	Clinical Oncology	Therapeutic modification of tumor hypoxia for radiotherapy resistance
40815459	2025	Review	Rev Med Inst Mex Seguro Soc	Physiology of altitude-related (hypobaric) hypoxia
24557798	2014	Commentary	J Applied Physiology	Perspective on hypoxia research translation
40347693	2025	Review	Redox Biology	Role of hypoxia in multiple sclerosis pathology

US Market Information

Ramipril currently has no market authorization records within the scope of this evidence pack (market status: Not Marketed, 0 licenses on file).

Safety Considerations

Please refer to the package insert for safety information. No key warnings, contraindications, or drug-drug interaction data were available in this evidence pack (all flagged as data gaps; DDI query returned “not found”).

Conclusion and Next Steps

Decision: Hold

Rationale: The TxGNN score is high, but evidence level is L5 — no clinical trials and no drug-specific literature support ramipril’s use in pulmonary hypertension owing to lung disease/hypoxia. The mechanistic rationale (RAAS inhibition reducing hypoxic vascular remodeling) is plausible but entirely theoretical given the retrieved evidence. Additionally, TFDA label safety data (DG001, Blocking) and MOA confirmation (DG002, High) are both missing, which independently blocks progression to a safety pre-assessment (S1) regardless of efficacy evidence.

To proceed, the following is needed:

Package insert / label data on warnings and contraindications (DG001 — blocking, required for S1 safety pre-assessment)
Confirmed mechanism of action from DrugBank or equivalent source (DG002)
Drug-specific (ramipril or ACE-inhibitor class) preclinical or clinical studies in pulmonary hypertension models/patients
Re-run literature search using drug + indication-specific search terms rather than generic hypoxia-biology terms, which returned only background/off-target results

Note for portfolio review: Other candidate indications for this same drug within the evidence pack carry meaningfully stronger, drug-specific evidence and may warrant separate evaluation — notably cerebral artery occlusion (rank 10, evidence level L3, includes a human comparative study of ramipril vs. enalapril on cerebral blood flow, PMID 8797135) and intracerebral hemorrhage (rank 8, evidence level L4, includes ramipril-specific animal mechanistic data, PMID 15721222).

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.