Lisinopril

證據等級: L5

預測適應症: 10 個

此 Evidence Pack 含 10 個 TxGNN 預測適應症；其中 8 個為 L5/S0（僅模型分數、無臨床試驗或文獻），僅 rank 7（septal MI）與 rank 9（chronic pulmonary heart disease）達 L3/S1。以下報告聚焦證據最完整的 rank 9：Chronic Pulmonary Heart Disease（唯一有 lisinopril 專屬文獻支持者）。

Lisinopril: From Hypertension/Heart Failure to Chronic Pulmonary Heart Disease

One-Sentence Summary

Lisinopril is an ACE inhibitor whose established uses are hypertension, heart failure and post-MI management (this Evidence Pack itself contains no jurisdiction-specific regulatory record of the original indication). The TxGNN model predicts potential efficacy for Chronic Pulmonary Heart Disease (chronic cor pulmonale), with 5 loosely-related clinical trials and 8 publications — including two drug-specific cohort studies on lisinopril in pulmonary hypertension/cor pulmonale — currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Not available in the regulatory data provided (New Zealand: not marketed); generically known as hypertension / heart failure / post-MI (ACE inhibitor class)
Predicted New Indication	Chronic Pulmonary Heart Disease
TxGNN Prediction Score	99.68%
Evidence Level	L3
New Zealand Market Status	✗ Not Marketed
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in this Evidence Pack (flagged as a High-severity data gap). Based on generally known pharmacology, lisinopril is an ACE inhibitor (ACEi): it blocks conversion of angiotensin I to angiotensin II, reducing systemic and pulmonary vascular resistance, afterload, and neurohormonal activation.

Chronic pulmonary heart disease (cor pulmonale) arises from sustained pulmonary hypertension secondary to chronic lung disease, leading to right ventricular strain. Because ACEi reduce vascular resistance and afterload — the same mechanism underlying their approved use in systemic hypertension and heart failure — extrapolation to the pulmonary vasculature is mechanistically plausible.

This plausibility is reinforced by two lisinopril-specific cohort studies in the evidence set (Pribylov 2006; Verbitskiĭ 2003), both reporting attenuation of pulmonary hypertension and improved right ventricular function in patients with chronic cor pulmonale/COPD. This is a materially stronger evidentiary basis than the other 9 candidates in this pack, which are supported only by TxGNN's prediction score with no drug-specific trials or literature (L5).

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT04486118	Phase 2	Active, not recruiting	36	Centrally-acting ACE inhibition for cognitive impairment in SLE — relevance graded C, not a lisinopril-specific or cor pulmonale trial
NCT03967496	N/A	Completed	402	Postoperative delirium incidence study — no direct relevance to lisinopril or cor pulmonale
NCT00982423	Phase 1/2	Completed	41	Furosemide dose effects on cardiorenal/humoral function in CHF — not a lisinopril trial
NCT06697353	N/A	Completed	4936	Real-world vericiguat outcomes in Japanese HFrEF patients — not a lisinopril trial
NCT00292162	N/A	Completed	41	Radiofrequency ablation for AF in advanced CHF — not a drug intervention trial

Note: None of the retrieved trials directly test lisinopril in chronic pulmonary heart disease; all are graded "C" (low direct relevance) in the source query.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
17047621	2006	Cohort	Kardiologiia	Lisinopril (10 mg/day) attenuated pulmonary hypertension and improved right ventricular systolic/diastolic function in heart failure patients with combined ischemic heart disease and COPD
14524095	2003	Cohort	Problemy tuberkuleza i boleznei legkikh	Lisinopril used in treatment of patients with chronic cor pulmonale
26895877	2016	Review	European journal of pediatrics	Reviews underuse of ACEi/ARB/mineralocorticoid antagonists in pediatric chronic heart failure
19393838	2009	Review	Clinical therapeutics	Review of nebivolol (beta-blocker), not lisinopril-specific
19592143	2009	Review	American journal of kidney diseases	Depression in CKD patients; case mentions ACEi use, not disease-focused
11170787	2001	Preclinical	Experimental and molecular pathology	Rat models of hypertension (aortic constriction, Goldblatt) and cardiopulmonary protein synthesis
20852161	2010	Case Report	American journal of health-system pharmacy	Hypotension/bradycardia from concomitant tizanidine + lisinopril — safety signal, not efficacy
32404370	2020	Case Report	BMJ case reports	Rare case of biventricular non-compaction; no direct lisinopril efficacy data

New Zealand Market Information

No marketing authorizations are currently on record — lisinopril is listed as not marketed in New Zealand in this dataset (0 licenses).

Safety Considerations

Please refer to the package insert for safety information. (No warnings, contraindications, or drug interaction data are available in this Evidence Pack; Medsafe/TFDA package-insert retrieval is flagged as a Blocking data gap — DG001.)

Conclusion and Next Steps

Decision: Hold

Rationale: Evidence level is L3, based on two older cohort studies (not RCTs) directly linking lisinopril to improved pulmonary hemodynamics in cor pulmonale, with no clinical trials specifically testing this drug-indication pair. A Blocking data gap (missing package-insert safety data) also prevents any S1 safety pre-assessment from being completed.

To proceed, the following is needed:

Medsafe/TFDA package insert (warnings, contraindications) — currently Blocking (DG001)
DrugBank-sourced mechanism of action confirmation — currently High-severity gap (DG002)
A prospective RCT or larger controlled cohort of lisinopril in chronic pulmonary heart disease/COPD-associated pulmonary hypertension
Route/formulation compatibility assessment, pending market authorization data
Disclaimer

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