Telmisartan
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Telmisartan: From Hypertension (ARB Class) to Cerebral Artery Occlusion
One-Sentence Summary
Telmisartan is an angiotensin II receptor blocker (ARB), a drug class established for hypertension management and cardiovascular risk reduction. The TxGNN model predicts potential benefit for Cerebral Artery Occlusion (ischemic stroke), currently the best-supported candidate among ten TxGNN predictions for this drug, backed by 3 clinical trials (including one completed Phase 4 study, n=1,228) and 16 preclinical/mechanistic publications.
Note: Of the 10 TxGNN-predicted indications in this evidence pack, the top-ranked hit (Prinzmetal angina, score 99.98%) and several others (brain stem infarction, ABri amyloidosis, Braddock syndrome, etc.) have no supporting trials or literature (Evidence Level L5, recommendation "Hold"). This report instead focuses on cerebral artery occlusion (rank 4), which has the strongest actual evidence base (L2). A related candidate, intracerebral hemorrhage (rank 9), has comparable evidence and is referenced below for context.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not formally recorded in this evidence pack — DrugBank indication lookup pending (see Data Gap DG002) |
| Predicted New Indication | Cerebral artery occlusion |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L2 |
| Taiwan Market Status | 未上市 (Not marketed) |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for telmisartan is not yet available in this evidence pack (Data Gap DG002, High severity — pending DrugBank API query). However, the repurposing rationale accompanying multiple predicted indications consistently describes telmisartan as an AT1 (angiotensin II type 1) receptor blocker, with additional PPAR-γ agonist activity — a dual profile sometimes referred to in the literature as a "metabosartan." This class is well established for blood pressure control and cardiovascular risk reduction.
Hypertension is a major upstream risk factor for both ischemic stroke (cerebral artery occlusion) and hemorrhagic stroke, so a drug that lowers blood pressure and improves endothelial function has a plausible pathway to benefit in cerebrovascular disease. Beyond blood-pressure lowering, telmisartan's AT1 blockade and PPAR-γ activation are reported in animal models to reduce oxidative stress, neuroinflammation, and infarct volume — mechanisms directly relevant to ischemic brain injury.
This mechanistic plausibility is supported by a substantial body of rodent middle cerebral artery occlusion (MCAO) studies showing reduced infarct volume, attenuated oxidative stress (AGE/4-HNE), and reduced neuroinflammatory markers (MCP-1, TNF-α, Iba-1) with telmisartan treatment. On the clinical side, a completed Phase 4 trial (NCT01075698, n=1,228) evaluated telmisartan's effect on cardiovascular biomarkers and events in high-risk hypertensive patients, providing some human translational support — though it was not designed specifically around cerebral artery occlusion as a primary endpoint. No dedicated Phase 2/3 RCT currently establishes telmisartan's efficacy for treating or preventing cerebral artery occlusion specifically.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01075698 | Phase 4 | Completed | 1,228 | Randomized, open-label (PROBE) comparison of telmisartan (ARB) vs. ordinary therapy in high-risk hypertensive patients; assessed cardiovascular biomarkers and long-term cardiovascular events. |
| NCT03785067 | Phase 3 | Terminated | 1 | TRIDENT cognitive sub-study on intensive BP control ("Triple Pill") for slowing memory decline post-ICH; terminated with only 1 participant enrolled. |
| NCT03783754 | N/A | Terminated | 4 | TRIDENT MRI sub-study evaluating structural brain changes with intensive BP control post-ICH; terminated with only 4 participants enrolled. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21901125 | 2011 | Review | PloS One | Head-to-head comparison of telmisartan vs. ramipril (and combination) for stroke prevention and neuroprotection in hypertensive rat stroke models. |
| 24780412 | 2014 | Animal Study | J Stroke Cerebrovasc Dis | Telmisartan reduced progressive oxidative stress and α-synuclein accumulation after transient MCAO in stroke-resistant hypertensive rats. |
| 25307428 | 2014 | Animal Study | J Stroke Cerebrovasc Dis | Long-term telmisartan ameliorated metabolic-syndrome-related molecules (insulin receptor, PPAR-γ, AT1R) after transient MCAO. |
| 19604102 | 2009 | Animal Study | J Neurotrauma | Telmisartan reduced cerebral infarct volume and peri-infarct cytosolic phospholipase A2 in experimental stroke. |
| 28699721 | 2016 | Animal Study | Indian J Exp Biol | Telmisartan + nimodipine combination showed neuroprotective effects when given pre- and post-ischemia in an experimental cerebral ischemia model. |
| 24650592 | 2014 | Animal Study | Pharmacol Biochem Behav | Non-hypotensive dose of telmisartan + nimodipine produced synergistic neuroprotection by attenuating brain cytokine levels after MCAO/reperfusion. |
| 32992165 | 2020 | Animal Study | J Stroke Cerebrovasc Dis | PPAR-γ activation by telmisartan inhibited Egr-1 and reduced brain injury in an experimental ischemic stroke model. |
| 25245484 | 2014 | Animal Study | J Stroke Cerebrovasc Dis | Telmisartan ameliorated inflammatory responses (MCP-1, TNF-α, Iba-1) after transient MCAO in hypertensive rats. |
| 24435631 | 2015 | Animal Study | Transl Stroke Res | Long-term telmisartan reduced Alzheimer's-type amyloid genesis after transient MCAO in stroke-resistant hypertensive rats. |
| 41341617 | 2025 | Animal/In silico Study | Toxicology Reports | Telmisartan (with ertugliflozin and omaveloxolone) attenuated cerebral ischemia-reperfusion neurotoxicity via Nrf2/HO-1 pathway modulation. |
(6 additional lower-priority animal studies with similar tMCAO/AT1-blockade mechanistic findings are available in the source evidence pack but omitted here for brevity.)
Taiwan Market Information
Telmisartan currently holds no drug license records in this evidence pack and is not marketed in Taiwan (0 authorizations). No product/dosage form information is available.
Safety Considerations
Please refer to the package insert for safety information. (Key warnings, contraindications, and drug-interaction data are currently unavailable — TFDA label parsing is flagged as a Blocking data gap; see Conclusion.)
Conclusion and Next Steps
Decision: Hold
Rationale: Evidence for cerebral artery occlusion is more substantial than for any other TxGNN prediction for this drug (L2, one completed Phase 4 trial plus consistent preclinical mechanistic support), but no dedicated Phase 2/3 RCT confirms efficacy for this specific indication, and telmisartan is not currently marketed in Taiwan — so there is no existing regulatory or supply pathway to build on.
To proceed, the following is needed:
- Resolve DG001 (Blocking): obtain and parse TFDA label warnings/contraindications before any S1 safety screening can occur
- Resolve DG002 (High): confirm original MOA and indication via DrugBank API query
- Clarify whether NCT01075698 captured cerebral artery occlusion/stroke as a distinct outcome (currently only described as general cardiovascular events/biomarkers)
- Evaluate feasibility and regulatory pathway for introducing telmisartan to the Taiwan market, since 0 licenses currently exist
- Consider whether a dedicated secondary-stroke-prevention RCT is warranted given the strength of preclinical signal
- Monitor intracerebral hemorrhage (rank 9, also L2) as a related candidate sharing the same RAAS-blockade rationale, anchored by the completed TRIDENT trial (NCT02699645, n=1,671)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.