Fimasartan

證據等級: L5

預測適應症: 10 個

Fimasartan: From Hypertension to Cerebrovascular Disorder

One-Sentence Summary

Fimasartan is a potent, long-acting angiotensin II type 1 (AT1) receptor blocker developed by Boryung Pharmaceutical (South Korea), approved there for the treatment of hypertension. The TxGNN model predicts it may be effective for cerebrovascular disorders — particularly ischemic stroke — with 2 clinical trials and 8 publications currently providing direct Fimasartan evidence for this indication. While TxGNN's top-scored prediction is pulmonary hypertension (score 99.20%), no Fimasartan-specific clinical data supports that direction; cerebrovascular disorder (rank #7, score 91.80%) represents the highest-evidence repurposing opportunity identified in this analysis.

Quick Overview

Item	Content
Original Indication	Hypertension (ARB class; not registered in Singapore — no local label available)
Predicted New Indication	Cerebrovascular Disorder (Ischemic Stroke / TIA)
TxGNN Prediction Score	91.80%
Evidence Level	L3
Singapore Market Status	Not marketed
Number of Registrations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Fimasartan is a selective AT1 receptor antagonist that blocks angiotensin II from binding to its primary cardiovascular receptor, thereby reducing vasoconstriction, lowering aldosterone secretion, and decreasing systemic vascular resistance. Its pharmacological profile mirrors other ARBs (losartan, valsartan, irbesartan) but with a reported higher binding affinity and longer duration of action. Although detailed mechanism of action data was not retrieved from DrugBank in this evidence pack, Fimasartan's pharmacological class is well-characterised in the published literature.

The mechanistic bridge between AT1 blockade and cerebrovascular protection is multi-layered and well-supported by Fimasartan-specific data. Four distinct pathways have been demonstrated: (1) blood pressure reduction and cerebral perfusion improvement — lowering systemic BP reduces cerebral artery wall stress, reducing long-term stroke risk; (2) NLRP3 inflammasome inhibition — animal studies show Fimasartan suppresses NLRP3-driven secondary neuroinflammation after both ischemic and hemorrhagic stroke; (3) anti-atherosclerotic activity — clinical imaging studies show Fimasartan reduces carotid plaque inflammation more effectively than amlodipine, addressing a key embolic stroke mechanism; and (4) blood pressure variability (BPV) reduction — a randomised trial demonstrates Fimasartan reduces BPV in acute stroke patients, and BPV is an independent predictor of stroke mortality and functional outcome.

Hypertension accounts for approximately 35–40% of stroke attributable risk. The step from antihypertensive treatment to cerebrovascular protection is therefore mechanistically natural rather than speculative. Fimasartan's advantages over established ARBs include its potency and extensive clinical study specifically in Korean stroke populations, providing a body of direct evidence that most repurposing candidates lack at this stage.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT03231293	Observational (N/A)	Completed	1,035	Multicenter longitudinal study evaluating effectiveness of Fimasartan-based antihypertensive treatment and prognosis in post-acute ischemic stroke or TIA patients, with 6-month follow-up. Largest real-world Fimasartan cerebrovascular dataset available.
NCT02403349	Phase 4	Unknown	105	FAVOR study: head-to-head comparison of Fimasartan, valsartan, and atenolol on central blood pressure, pulse wave velocity, flow-mediated dilation, and cerebral blood flow (transcranial Doppler) in acute ischemic stroke with hypertension. Status requires clarification — results published as PMID 29367614.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
31772615	2019	RCT (Double-blind)	Cardiovascular Therapeutics	80 acute ischemic stroke patients randomised to Fimasartan or valsartan for 8 weeks. Compared blood pressure variability (BPV) — a key independent predictor of stroke mortality and functional outcome.
29367614	2018	Clinical Study (Double-blind)	Scientific Reports	FAVOR study (n=105): Fimasartan, atenolol, and valsartan compared on central and cerebral haemodynamic parameters over 12 weeks in hypertensive ischaemic stroke patients. Direct Fimasartan cerebrovascular haemodynamics data.
30537083	2019	Clinical Comparative Study	Clinical Cardiology	Fimasartan vs. amlodipine on carotid atherosclerotic plaque inflammation assessed by imaging. RAAS inhibition via Fimasartan demonstrated superior anti-inflammatory plaque effects relevant to embolic stroke prevention.
37365730	2023	Clinical Cohort Study	Journal of Korean Medical Science	Fimasartan vs. other ARBs in heart failure after acute myocardial infarction — provides comparative effectiveness data establishing Fimasartan within the ARB class in high-cardiovascular-risk settings.
30171865	2018	Animal Study	Experimental Neurology	Fimasartan pretreatment ameliorated NLRP3 inflammasome-mediated neuroinflammation and reduced brain injury volume after intracerebral haemorrhage in animal model — direct neuroprotective mechanistic evidence.
31307370	2019	Animal Study	Molecular Medicine	Fimasartan reduced neointimal formation and systemic inflammation after carotid arterial injury in ApoE knockout mice, supporting an anti-atherosclerotic mechanism of relevance to stroke prevention.
26448932	2015	Animal Study	BioMed Research International	Long-term Fimasartan treatment (0.5–3 mg/kg) reduced infarct volume and improved functional outcomes after transient middle cerebral artery occlusion in rats.
26608500	2016	In Vitro Study	Inflammation Research	Fimasartan modulated hemolysate-induced inflammation in astrocytes via Akt, ERK, and NFκB pathways — mechanistic evidence for neuroprotection in the hemorrhagic stroke microenvironment.

Singapore Market Information

Fimasartan is not currently registered with HSA and has no approved licenses in Singapore. No authorisation numbers, product names, or local indications are on record. Any clinical use in Singapore would require either an importation licence or a clinical trial authorisation from HSA.

Safety Considerations

Detailed safety data (package insert warnings, contraindications, drug interaction profile) was not available in this evidence pack. As a general ARB class note relevant to the cerebrovascular indication:

ARBs are contraindicated in pregnancy (all trimesters)
Bilateral renal artery stenosis is a contraindication — acute renal failure risk (particularly relevant to Rank 4 predicted indication: malignant renovascular hypertension, which should be excluded from any repurposing trial)
Acute-phase stroke management with antihypertensives requires careful BP target selection — aggressive lowering may worsen ischaemia

Please refer to the Boryung package insert and HSA import documentation for the full safety profile before any clinical application.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Fimasartan has accumulating direct clinical evidence in cerebrovascular settings — including a completed large observational study (n=1,035) and a double-blind Phase 4 RCT design comparing it head-to-head against valsartan in ischemic stroke. The mechanistic basis (AT1 blockade → reduced BPV, anti-atherosclerosis, NLRP3 neuroprotection) is supported by both clinical and preclinical Fimasartan-specific data, placing this above a class-effect extrapolation. This is the highest-quality repurposing signal in the current evidence pack.

To proceed, the following is needed:

Regulatory pathway: Confirm HSA importation or clinical trial authorisation process — no Singapore registration exists; a therapeutic product import licence or CTA will be required
Safety dossier: Retrieve the full package insert (MOA, contraindications, warnings) from the Boryung Korea label or DrugBank — currently a high-severity data gap flagged in the evidence pack
FAVOR study clarification: Obtain published outcomes from NCT02403349 (currently "Unknown" status) to determine whether primary endpoints support cerebrovascular efficacy
Indication precision: Define whether the target is (a) secondary stroke prevention, (b) acute ischemic stroke management, or (c) broad cerebrovascular risk reduction — each requires a different trial design and regulatory pathway
Drug interaction assessment: Fimasartan + anticoagulants (warfarin, DOACs) and antiplatelets (aspirin, clopidogrel) are co-prescriptions in stroke patients; DDI data was not found in this evidence pack and must be obtained
Dose optimisation: Published Fimasartan studies use various dose ranges (30–120 mg); a dose-finding study or review of existing PK data for the stroke population is warranted before proceeding to an efficacy trial
Disclaimer

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