Ticagrelor
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Ticagrelor: From Acute Coronary Syndrome to Intracranial Arteriosclerosis
One-Sentence Summary
Ticagrelor is a P2Y12 receptor antagonist established as a core antiplatelet therapy in acute coronary syndrome (ACS) and related atherothrombotic disease. The TxGNN model predicts it may also be effective for Intracranial Arteriosclerosis (intracranial atherosclerotic disease), with 11 clinical trials and 3 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute Coronary Syndrome (ACS) — established antiplatelet indication referenced throughout the evidence pack (e.g. PLATO, PEGASUS-TIMI 54, THEMIS trials); official UK label text not yet obtained (data gap) |
| Predicted New Indication | Intracranial Arteriosclerosis (intracranial atherosclerotic disease) |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L2 |
| UK Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data from DrugBank has not been obtained (data gap DG002). Based on information available within the evidence pack, ticagrelor is a reversible P2Y12 receptor antagonist that inhibits ADP-induced platelet activation and aggregation. This mechanism underlies its established role in acute coronary syndrome and broader atherothrombotic disease, where large Phase 3 trials (PLATO, THEMIS, EUCLID) have confirmed efficacy and safety of ticagrelor-based antiplatelet regimens.
Intracranial arteriosclerosis (intracranial atherosclerotic disease, ICAD) shares the same underlying pathology — atherosclerotic plaque causing thrombotic vessel narrowing — as coronary and peripheral artery disease, just in a different vascular bed. Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is already the standard short-term treatment for symptomatic ICAD, and several ongoing trials (e.g. CAPTIVA, DREAM-PRIDE) are now testing whether ticagrelor-containing regimens can outperform standard clopidogrel-based DAPT in this population, since recurrent stroke risk remains high even with current therapy.
Mechanistically this is a logical extension of ticagrelor’s established antiplatelet action rather than a disease-specific mechanism — the rationale rests on the shared atherothrombotic biology across vascular beds, supported directly by active Phase 3 clinical development in ICAD.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT04948749 | N/A | Recruiting | 792 | DREAM-PRIDE: drug-eluting stent + aggressive medical treatment vs standard medical treatment alone for preventing 1-year stroke recurrence in symptomatic intracranial atherosclerotic disease |
| NCT05047172 | Phase 3 | Active, not recruiting | 1,683 | CAPTIVA: compares anticoagulation vs antiplatelet regimens (including ticagrelor) vs clopidogrel for lowering 1-year rate of ischaemic stroke, intracerebral haemorrhage, or vascular death in intracranial vascular atherostenosis |
| NCT02605447 | Phase 4 | Completed | 2,009 | EVOLVE Short DAPT: assessed safety of 3-month DAPT in high bleeding-risk patients undergoing PCI with an everolimus-eluting stent; informs DAPT duration strategies relevant to intracranial stenting |
| NCT01732822 | Phase 3 | Completed | 13,885 | Compared ticagrelor vs clopidogrel on cardiovascular death, MI and ischaemic stroke risk in peripheral artery disease; evidence-pack relevance notes overlap with ischaemic stroke/TIA populations |
| NCT01813435 | Phase 3 | Completed | 15,991 | GLOBAL LEADERS: ticagrelor+aspirin for 1 month then ticagrelor alone vs standard DAPT after stent implantation; general PCI population, not intracranial-specific |
| NCT06714526 | N/A | Recruiting | 100 | Pilot RCT comparing genotype-guided P2Y12 inhibitor selection vs conventional clopidogrel in symptomatic intracranial atherosclerotic disease |
| NCT06058130 | N/A | Unknown | 2,171 | Compares anticoagulation alone vs anticoagulation + antiplatelet therapy in acute ischaemic stroke patients with concomitant non-valvular atrial fibrillation and extracranial/intracranial artery stenosis |
| NCT07354828 | N/A | Not yet recruiting | 3,500 | Establishes quality-control standards for DAPT-based coronary revascularisation in high bleeding-risk CAD/ACS patients; general framework, not intracranial-specific |
| NCT06857045 | N/A | Withdrawn | 0 | Planned comparison of 3 vs 6 months DAPT after NOVA intracranial sirolimus-eluting stent implantation; trial withdrawn before enrolment |
| NCT03620760 | Phase 4 | Unknown | 2,036 | Low-dose vs standard-dose ticagrelor in unstable angina patients after drug-eluting stent implantation |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39862061 | 2025 | RCT (trial design) | International Journal of Stroke | Describes design and early progress of the CAPTIVA trial comparing alternative dual antithrombotic regimens against standard clopidogrel + aspirin for symptomatic intracranial atherosclerotic stenosis; notes recurrent stroke risk remains high up to 12 months with current standard therapy |
| 38252758 | 2024 | Review | Stroke | Focused update summarising highlights and knowledge gaps in intracranial atherosclerosis management |
| 39658130 | 2025 | Cohort/Clinical study | Journal of NeuroInterventional Surgery | Reports clinical experience with ticagrelor 60 mg twice daily + aspirin 81 mg vs standard aspirin + clopidogrel for intracranial stenting, highlighting ticagrelor’s rapid onset and consistent platelet inhibition |
UK Market Information
Ticagrelor does not currently hold a marketing authorisation in the United Kingdom under this evidence pack (market status: not marketed; total authorisations: 0). No product licences, brand names, or approved indication text are available in the current dataset.
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
Note: TFDA/MHRA-equivalent warnings and contraindications for ticagrelor have not yet been obtained in this evidence pack (data gap DG001, flagged as Blocking) — this must be resolved before any safety-related decision can proceed.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The predicted indication is supported by a Phase 3, actively recruiting trial (CAPTIVA) directly testing ticagrelor-containing regimens in intracranial atherosclerotic stenosis, plus a coherent mechanistic rationale extending ticagrelor’s established antiplatelet role in atherothrombotic disease. However, evidence level is L2 (a single relevant ongoing/completed trial population rather than confirmed Phase 3 RCT results), and the drug currently has no UK marketing authorisation.
To proceed, the following is needed:
- UK SmPC/BNF warnings and contraindications for ticagrelor (data gap DG001, Blocking — required before any safety evaluation)
- Confirmed mechanism of action data from DrugBank (data gap DG002)
- Mature efficacy results from CAPTIVA (estimated completion 2028-05-31) and DREAM-PRIDE (estimated completion 2026-12)
- Clarification of the UK regulatory pathway, given ticagrelor is not currently marketed in the UK
- Formal drug-drug interaction data (current DDI query returned no results)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.