Ticagrelor
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Ticagrelor: From Acute Coronary Syndrome to Intracranial Arteriosclerosis
One-Sentence Summary
Ticagrelor is a P2Y12 receptor antagonist established for antiplatelet therapy in acute coronary syndrome (ACS) and related atherothrombotic conditions. The TxGNN model predicts it may be effective for Intracranial Arteriosclerosis, with 10 clinical trials and 3 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute Coronary Syndrome (ACS) / secondary prevention of atherothrombotic events — this is Ticagrelor’s globally established core indication; no TFDA-approved indication text is available because the drug is not currently marketed in Taiwan |
| Predicted New Indication | Intracranial Arteriosclerosis |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L1 |
| Taiwan Market Status | Not marketed (Not Marketed) |
| Number of Registrations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, TFDA-sourced mechanism of action data is not available for Ticagrelor (Data Gap DG002). Based on information contained in this evidence pack’s repurposing rationale, Ticagrelor acts as a P2Y12 receptor antagonist, reducing platelet activation and aggregation — the standard antiplatelet mechanism used to prevent atherothrombotic events in ACS.
Intracranial arteriosclerosis (intracranial atherosclerotic disease, ICAD) causes ischemic stroke through the same underlying pathology as coronary and peripheral atherosclerosis: platelet-mediated thrombus formation at a stenotic/plaque site. Since Ticagrelor’s core validated mechanism directly targets this platelet-aggregation pathway, its extension from coronary/peripheral arterial disease to intracranial arteriosclerosis is mechanistically coherent rather than incidental.
This is further supported by the fact that large, direct-comparison Phase 3 trials (e.g., SOCRATES-type ischemic stroke/TIA populations, EUCLID in peripheral artery disease, and the ongoing CAPTIVA trial specifically in intracranial vascular atherostenosis) already test P2Y12 inhibitor strategies including ticagrelor in cerebrovascular atherosclerotic populations, reinforcing the biological plausibility of the TxGNN prediction.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT06714526 | NA | Recruiting | 100 | Genotype-guided P2Y12 inhibitor selection vs. conventional clopidogrel in symptomatic ICAD |
| NCT04948749 | NA | Recruiting | 792 | DREAM-PRIDE: drug-eluting stent + aggressive medical treatment vs. medical treatment alone for ICAD |
| NCT02605447 | Phase 4 | Completed | 2,009 | EVOLVE Short DAPT: 3-month dual antiplatelet therapy safety in high bleeding-risk PCI patients |
| NCT01732822 | Phase 3 | Completed | 13,885 | Ticagrelor vs. clopidogrel on CV death/MI/ischemic stroke risk in peripheral artery disease |
| NCT05047172 | Phase 3 | Active, not recruiting | 1,683 | CAPTIVA: rivaroxaban/ticagrelor vs. clopidogrel for lowering 1-year stroke/hemorrhage/vascular death in intracranial vascular atherostenosis |
| NCT01813435 | Phase 3 | Completed | 15,991 | GLOBAL LEADERS: ticagrelor+aspirin (1 mo) then ticagrelor alone vs. standard DAPT post-stenting |
| NCT06058130 | NA | Unknown | 2,171 | Anticoagulation vs. anticoagulation+antiplatelet in acute ischemic stroke with AF and extracranial/intracranial stenosis |
| NCT07354828 | N/A | Not yet recruiting | 3,500 | Quality control standard system for DAPT-based coronary revascularization |
| NCT06857045 | NA | Withdrawn | 0 | 3- vs 6-month DAPT after NOVA intracranial sirolimus-eluting stent implantation (trial withdrawn) |
| NCT03620760 | Phase 4 | Unknown | 2,036 | Low-dose vs. standard-dose ticagrelor after DES implantation for unstable angina |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39862061 | 2025 | Trial design paper (CAPTIVA) | International Journal of Stroke | Describes rationale/design of CAPTIVA trial comparing antithrombotic regimens (incl. ticagrelor) for symptomatic intracranial atherosclerotic stenosis |
| 39658130 | 2025 | Cohort | Journal of Neurointerventional Surgery | Lower-dose ticagrelor (60 mg BID) + aspirin compared with standard aspirin/clopidogrel for neurointerventional stenting |
| 38252758 | 2024 | Review | Stroke | Focused update on intracranial atherosclerosis: highlights and knowledge gaps in antithrombotic management |
Taiwan Market Information
Ticagrelor currently holds no TFDA drug license and is not marketed in Taiwan (0 registrations). No product/indication license data is available for extraction.
Safety Considerations
Drug Interactions: A total of 423 documented interactions are on record. Notable examples from the sample data include:
| Interacting Drug | Interaction Level |
|---|---|
| Clarithromycin | Major |
| Aprepitant, Morphine, Acetylsalicylic acid, Dexamethasone, Budesonide, Saxagliptin, Eliglustat, Naldemedine, Metreleptin, Miconazole, Nitisinone, Rolapitant, Simvastatin, Cisapride, Clotrimazole, Dexfenfluramine | Moderate |
| Naloxegol, Prucalopride | Minor |
Given the strong CYP3A4 involvement suggested by the Clarithromycin (Major) interaction, CYP3A4 inhibitors/inducers and concomitant strong bleeding-risk agents should be reviewed carefully in any repurposing protocol.
Detailed TFDA label warnings and contraindications are not yet available (Data Gap DG001, Blocking) — this must be resolved before any Stage 1 safety assessment can proceed.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The mechanistic link is strong and directly relevant (P2Y12-mediated antiplatelet action addresses the core thrombotic pathology of intracranial arteriosclerosis), and evidence level is L1, supported by completed Phase 3 trials (EUCLID, GLOBAL LEADERS) plus an actively running dedicated Phase 3 trial (CAPTIVA) in this exact population. However, Ticagrelor is not currently marketed in Taiwan and TFDA safety labeling is unavailable, so this cannot yet advance past the guardrail stage.
To proceed, the following is needed:
- TFDA package insert / warnings & contraindications data (DG001 — Blocking; required for Stage 1 safety assessment)
- Formal DrugBank/TFDA-sourced mechanism of action documentation (DG002 — High priority)
- CAPTIVA trial (NCT05047172) completion data (expected 2028) as the pivotal confirmatory readout for this indication
- A Taiwan regulatory pathway assessment, since market entry (new drug application or expanded indication filing) has not yet occurred
Note: Other TxGNN-predicted indications for Ticagrelor in this evidence pack (e.g., Monckeberg arteriosclerosis, May-Thurner syndrome, livedo reticularis, angiodysplasia) carry L4–L5 evidence with no direct clinical support and are recommended for Hold pending further mechanistic or clinical validation.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.