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 whose established antiplatelet use targets atherothrombotic events in coronary artery disease (as referenced across the repurposing rationale in this evidence pack); detailed EU regulatory documentation for the original indication is not available in this dataset. The TxGNN model predicts it may also be effective for Intracranial Arteriosclerosis, with 11 clinical trials and 3 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not documented in EU regulatory data; inferred from evidence-pack rationale as antiplatelet therapy for atherothrombotic coronary/cardiovascular disease (ACS, PCI-treated ischemic heart disease) |
| Predicted New Indication | Intracranial Arteriosclerosis |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L2 |
| EU Market Status | Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data for ticagrelor is not available in this evidence pack (flagged as a High-severity data gap). Based on information embedded in the repurposing rationale, ticagrelor is a P2Y12 receptor antagonist — an antiplatelet agent that inhibits ADP-mediated platelet activation and aggregation. Its efficacy in atherothrombotic coronary disease (acute coronary syndrome, post-PCI thrombosis prevention) is an established use pattern reflected repeatedly across the evidence for this candidate.
Intracranial arteriosclerosis and coronary/peripheral artery atherosclerosis share the same underlying pathophysiology: atherosclerotic plaque formation followed by platelet-driven thrombus formation that precipitates ischemic events (myocardial infarction in the coronary bed, ischemic stroke in the intracranial bed). Because P2Y12 inhibition addresses the thrombotic component common to atherosclerotic disease regardless of vascular territory, the mechanistic rationale for extending ticagrelor to intracranial arteriosclerosis is biologically plausible.
This is further supported by an active dedicated trial base: the CAPTIVA trial (NCT05047172, Phase 3) is directly comparing ticagrelor, rivaroxaban, and clopidogrel for lowering 1-year rates of ischemic stroke, intracerebral hemorrhage, or vascular death in intracranial vascular atherostenosis, and the DREAM-PRIDE trial (NCT04948749) is evaluating aggressive medical treatment (including antiplatelet therapy) for symptomatic intracranial atherosclerotic disease. Both are grade-A relevance but still recruiting, which is why the current evidence level is capped at L2 rather than L1.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05047172 | Phase 3 | Recruiting | 1,683 | CAPTIVA trial — compares rivaroxaban, ticagrelor, or both vs. clopidogrel for lowering 1-year ischemic stroke/hemorrhage/vascular death in intracranial vascular atherostenosis (grade A) |
| NCT04948749 | N/A | Recruiting | 792 | DREAM-PRIDE trial — evaluates drug-eluting stent plus aggressive medical treatment vs. standard medical treatment for preventing recurrent stroke in symptomatic intracranial atherosclerotic disease (grade A) |
| NCT01732822 | Phase 3 | Completed | 13,885 | EUCLID trial — ticagrelor vs. clopidogrel in peripheral artery disease for cardiovascular death, MI, and ischemic stroke; overlapping atherosclerotic population but not intracranial-specific (grade B) |
| NCT01813435 | Phase 3 | Completed | 15,991 | GLOBAL LEADERS trial — ticagrelor + aspirin (1 month) then ticagrelor monotherapy vs. standard DAPT after stenting; related mechanism, different vascular bed (grade C) |
| NCT02605447 | Phase 4 | Completed | 2,009 | EVOLVE Short DAPT Study — safety of 3-month DAPT in high bleeding-risk PCI patients with SYNERGY stent |
| NCT06058130 | N/A | Unknown | 2,171 | Anticoagulation vs. anticoagulation + antiplatelet therapy in acute ischemic stroke with concomitant NVAF and extracranial/intracranial artery stenosis |
| NCT07354828 | N/A | Not Yet Recruiting | 3,500 | Quality control indicator optimization for coronary revascularization based on DAPT |
| NCT03620760 | Phase 4 | Unknown | 2,036 | Low-dose vs. standard-dose ticagrelor in unstable angina after drug-eluting stent implantation |
| NCT06714526 | N/A | Recruiting | 100 | Genotype-guided P2Y12 inhibitor selection vs. conventional clopidogrel in symptomatic intracranial atherosclerotic disease (pilot study) |
| NCT07164859 | Phase 3 | Not Yet Recruiting | 1,700 | SOLOPCI — very short DAPT followed by P2Y12 monotherapy in older PCI patients |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39862061 | 2025 | RCT Protocol | International Journal of Stroke | Describes the design of the CAPTIVA trial comparing dual antithrombotic regimens (including ticagrelor) against clopidogrel + aspirin for symptomatic intracranial atherosclerotic stenosis, given persistent recurrent-stroke risk with standard therapy |
| 39658130 | 2025 | Cohort | Journal of Neurointerventional Surgery | Reports experience with lower-dose ticagrelor (60 mg BID) plus aspirin vs. standard aspirin/clopidogrel DAPT for intracranial stenting, noting ticagrelor’s rapid, consistent platelet inhibition |
| 38252758 | 2024 | Review | Stroke | Focused update summarizing knowledge gaps in intracranial atherosclerosis management, providing context for ongoing antiplatelet trial designs |
EU Market Information
Ticagrelor is recorded as Not Marketed in this evidence pack, with 0 marketing authorizations on file. No EU authorization numbers, product names, or approved indication texts are available for citation.
Safety Considerations
Please refer to the SmPC for safety information.
Conclusion and Next Steps
Decision: Hold (corresponds to decision stage S2 / “Research Question” in the underlying scoring framework)
Rationale:
- Evidence level is L2 — only one completed Phase 3 RCT (EUCLID) has population overlap with atherosclerotic disease, but it was conducted in peripheral artery disease, not intracranial arteriosclerosis specifically (grade B relevance).
- The two trials most directly relevant to this indication — CAPTIVA (Phase 3) and DREAM-PRIDE — are both still recruiting, so disease-specific efficacy/safety data for ticagrelor in intracranial arteriosclerosis are not yet available.
- Critical drug-level safety data (TFDA/EU label warnings and contraindications — flagged as a Blocking data gap) and mechanism-of-action documentation (High-severity data gap) are both missing, preventing a formal S1 safety pre-assessment.
To proceed, the following is needed:
- Resolve DG001 (Blocking): obtain official label warnings/contraindications to enable S1 safety screening.
- Resolve DG002 (High): confirm detailed mechanism of action via DrugBank/regulatory sources.
- EU marketing authorization details (product names, approved indication text, dosage forms) to establish actual regulatory status, since this pack shows the drug as unmarketed.
- Await completion and results of the CAPTIVA (NCT05047172) and DREAM-PRIDE (NCT04948749) trials, which are the only Phase 3/near-Phase 3 studies directly testing antiplatelet therapy (including ticagrelor) for intracranial atherosclerotic disease.
- Drug interaction (DDI) data, currently unavailable, before any clinical guardrails can be defined.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.