Trials for ticagrelor
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ticagrelor clinical trials
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ticagrelor PLATO PEGASUS SOCRATES landmark trials
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ticagrelor PLATO acute coronary syndromes
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ticagrelor PEGASUS myocardial infarction secondary prevention
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ticagrelor SOCRATES stroke TIA
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ticagrelor stroke transient ischemic attack SOCRATES
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ticagrelor peripheral artery disease EUCLID
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I now have comprehensive data across all major ticagrelor trials. Let me compile the full summary.
Ticagrelor — Major Clinical Trials
Ticagrelor is an oral, reversible, direct-acting P2Y12 (ADP receptor) inhibitor that does not require hepatic activation, giving it faster onset and more predictable platelet inhibition than clopidogrel. — Braunwald's Heart Disease & Harrison's Principles of Internal Medicine 22E
1. PLATO — The Landmark ACS Trial
Full name: Platelet Inhibition and Patient Outcomes
Published: NEJM 2009 | PMID: 19717846
| Feature | Details |
|---|---|
| Population | 18,624 patients hospitalized with ACS (STEMI and NSTEMI) |
| Design | Multicenter, double-blind RCT |
| Comparison | Ticagrelor 180 mg load → 90 mg BID vs Clopidogrel 300–600 mg load → 75 mg OD |
| Duration | 12 months |
| Primary endpoint | CV death + MI + stroke |
Results:
- Primary endpoint: 9.8% ticagrelor vs 11.7% clopidogrel (HR 0.84; 95% CI 0.77–0.92; P<0.001)
- CV death: 4.0% vs 5.1% (P=0.001)
- MI: 5.8% vs 6.9% (P=0.005)
- All-cause death: 4.5% vs 5.9% (P<0.001)
- Major bleeding: no significant difference (11.6% vs 11.2%; P=0.43)
- Non-CABG major bleeding: higher with ticagrelor (4.5% vs 3.8%; P=0.03)
Verdict: Ticagrelor superior to clopidogrel in ACS across the spectrum. Benefit extended to patients managed medically, with PCI, and with CABG. This trial formed the basis for guideline preference for ticagrelor over clopidogrel in high-risk ACS.
2. PEGASUS-TIMI 54 — Long-Term Secondary Prevention
Full name: Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54
Published: NEJM 2015 | PMID: 25773268
| Feature | Details |
|---|---|
| Population | 21,162 patients with MI 1–3 years prior |
| Design | Double-blind, 1:1:1 RCT |
| Comparison | Ticagrelor 90 mg BID vs Ticagrelor 60 mg BID vs Placebo (all on low-dose aspirin) |
| Duration | Median 33 months |
Results:
- Primary endpoint (CV death + MI + stroke) at 3 years:
- 7.85% (90 mg) vs 7.77% (60 mg) vs 9.04% (placebo)
- HR for 90 mg vs placebo: 0.85 (P=0.008)
- HR for 60 mg vs placebo: 0.84 (P=0.004)
- TIMI major bleeding: 2.60% (90 mg), 2.30% (60 mg), 1.06% (placebo) — both P<0.001 vs placebo
- Intracranial/fatal bleeding: similar across all arms (~0.6–0.7%)
Verdict: Long-term ticagrelor (especially the 60 mg BID dose given its similar efficacy with a slightly lower bleeding rate) reduces recurrent MACE in stable post-MI patients. The 60 mg BID dose is now the approved dose for this indication.
3. SOCRATES — Ticagrelor in Stroke/TIA
Full name: Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes
Published: NEJM 2016 | PMID: 27160892
| Feature | Details |
|---|---|
| Population | 13,199 patients with non-severe ischemic stroke or high-risk TIA |
| Design | International double-blind RCT (33 countries) |
| Comparison | Ticagrelor 180 mg load → 90 mg BID vs Aspirin 300 mg → 100 mg OD |
| Duration | 90 days |
Results:
- Primary endpoint (stroke + MI + death): 6.7% ticagrelor vs 7.5% aspirin (HR 0.89; P=0.07) — not significant
- Ischemic stroke: 5.8% vs 6.7% (HR 0.87; P=0.05) — trend only
- Major bleeding: low and similar (0.5% vs 0.6%)
Subgroup finding: A Lancet Neurology 2017 post-hoc analysis (PMID: 28238711) showed benefit in the atherosclerotic stroke subgroup (HR 0.78; P=0.02), which shaped subsequent trial design.
Verdict: Ticagrelor monotherapy was not superior to aspirin in unselected acute stroke/TIA. The atherosclerotic subgroup signal drove the design of THALES.
4. EUCLID — Peripheral Artery Disease
Full name: Examining Use of tiCagreLor In paD
Published: NEJM 2017 | PMID: 27959717
| Feature | Details |
|---|---|
| Population | 13,885 patients with symptomatic PAD (ABI ≤0.80 or prior lower limb revascularization) |
| Design | Double-blind, event-driven RCT |
| Comparison | Ticagrelor 90 mg BID vs Clopidogrel 75 mg OD (monotherapy) |
| Duration | Median 30 months |
Results:
- Primary endpoint (CV death + MI + ischemic stroke): 10.8% vs 10.6% (HR 1.02; P=0.65) — no difference
- Acute limb ischemia: 1.7% each (HR 1.03; P=0.85)
- Major bleeding: 1.6% each (HR 1.10; P=0.49)
Verdict: Ticagrelor was not superior to clopidogrel in PAD. Clopidogrel remains standard for this indication.
5. TWILIGHT — P2Y12 Monotherapy After PCI
Full name: Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention
Published: NEJM 2019 | PMID: 31556978
| Feature | Details |
|---|---|
| Population | 7,119 high-risk patients post-PCI (drug-eluting stent), completed 3 months DAPT without events |
| Design | Double-blind RCT |
| Comparison | Ticagrelor + placebo vs Ticagrelor + aspirin for 1 year |
Results:
- Primary endpoint (BARC 2/3/5 bleeding): 4.0% ticagrelor alone vs 7.1% DAPT (HR 0.56; P<0.001) — 44% relative reduction
- BARC 3/5 bleeding: 1.0% vs 2.0% (HR 0.49)
- Death/MI/stroke (noninferiority met): 3.9% vs 3.9%
Verdict: After 3 months of DAPT, dropping aspirin and continuing ticagrelor monotherapy significantly reduces bleeding without compromising ischemic protection. This supports the de-escalation strategy in PCI.
6. ULTIMATE-DAPT — Further De-escalation Evidence
Published: Lancet 2024 | PMID: 38599220
| Feature | Details |
|---|---|
| Population | ACS patients post-PCI, completing 1 month DAPT |
| Comparison | Ticagrelor alone (months 1–12) vs Ticagrelor + aspirin |
Results: Ticagrelor monotherapy from month 1–12 reduced major bleeding (primary endpoint met) with non-inferior ischemic outcomes — supporting even earlier aspirin withdrawal.
7. POPular AGE — Elderly Patients
Published: Lancet 2020 | PMID: 32334703
| Feature | Details |
|---|---|
| Population | 1,002 patients ≥70 years with NSTE-ACS |
| Comparison | Clopidogrel vs Ticagrelor or Prasugrel |
Results: Clopidogrel was non-inferior for the combined endpoint of net clinical benefit (all bleeding + MACE), with significantly less bleeding. Ticagrelor/prasugrel did not confer net benefit over clopidogrel in elderly NSTE-ACS patients.
Verdict: In patients ≥70 with NSTE-ACS, clopidogrel may be preferable to ticagrelor due to the higher bleeding burden in this population.
Recent Meta-Analytic Evidence
| Study | PMID | Key Finding |
|---|---|---|
| Valgimigli et al., JAMA Cardiol 2024 | 38506796 | Patient-level meta-analysis: ticagrelor/clopidogrel monotherapy after PCI reduces bleeding vs DAPT; ticagrelor monotherapy showed lower mortality trend |
| Valgimigli et al., Lancet 2024 | 39226909 | De-escalation to ticagrelor monotherapy reduces bleeding in both ACS and non-ACS, confirms benefit |
| Lee et al., Ann Intern Med 2025 | 39961108 | Individual patient data meta-analysis confirms de-escalation to ticagrelor mono in ACS is safe and reduces bleeding |
| Geravandi et al., BMC Pharmacol 2024 | 39654024 | Ticagrelor superior to clopidogrel in STEMI (systematic review) |
Summary Table
| Trial | Setting | Comparator | Result |
|---|---|---|---|
| PLATO (2009) | ACS (STEMI/NSTEMI) | Clopidogrel | ✅ Ticagrelor superior — reduced CV death, MI, stroke |
| PEGASUS-TIMI 54 (2015) | Post-MI (≥1 yr), stable | Placebo + aspirin | ✅ Ticagrelor 60 mg BID reduced MACE; more bleeding |
| SOCRATES (2016) | Acute stroke / TIA | Aspirin | ❌ Not superior overall; trend in atherosclerotic subgroup |
| EUCLID (2017) | Symptomatic PAD | Clopidogrel | ❌ Not superior; no difference in limb events or bleeding |
| TWILIGHT (2019) | High-risk post-PCI | Ticagrelor + aspirin | ✅ Ticagrelor monotherapy: less bleeding, non-inferior ischemic |
| POPular AGE (2020) | NSTE-ACS, age ≥70 | Ticagrelor/prasugrel | ⚠️ Clopidogrel better net clinical benefit in elderly |
| ULTIMATE-DAPT (2024) | ACS post-PCI | Ticagrelor + aspirin | ✅ Earlier aspirin withdrawal (1 mo) safe, reduces bleeding |
Key side effects across trials: Dyspnea (up to 15%), asymptomatic ventricular pauses, and increased non-CABG bleeding. Platelet transfusion does not reverse ticagrelor (reversal agent bentracimab is in development). — Harrison's 22E, Braunwald's Heart Disease
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