To Compare the Pharmacodynamic and Short-term Clinical Effects of Standard DAPT, DAPT With Half-dose Ticagrelor, and Aspirin-free Half-dose Ticagrelor Monotherapy From the Day of PCI in Chronic Coronary Syndrome (CCS)

Half-dose Ticagrelor Monotherapy Versus Standard Dual Antiplatelet Therapy in Chronic Coronary Syndrome After Percutaneous Coronary Intervention: a Randomised Pilot Trial With PRU-guided Pharmacodynamic Assessment

Six months of aspirin plus clopidogrel remains the recommended antiplatelet regimen after percutaneous coronary intervention (PCI) for chronic coronary syndrome (CCS), with the more potent P2Y₁₂ inhibitors reserved for the acute coronary syndromes (ACS) that produced their pivotal evidence. Yet the contemporary landscape of post-PCI antithrombotic therapy has shifted considerably since PLATO and TRITON-TIMI 38, and the conventional algorithm sits increasingly uneasily with two well-established realities. The first is the now consistent demonstration that aspirin contributes more to bleeding than to ischemic protection in patients adequately treated with a P2Y₁₂ inhibitor. TWILIGHT, TICO, T-PASS, ULTIMATE-DAPT and GLOBAL LEADERS have, in sequence, established that withdrawing aspirin after a defined period of P2Y₁₂-based DAPT reduces clinically relevant bleeding without an excess of ischemic events. Each of these trials, however, retained ticagrelor at the standard 90 mg twice-daily dose, required a run-in of conventional DAPT before aspirin was stopped, and enrolled populations dominated by ACS.

The second is the persistent and now mechanistically grounded observation that East-Asian patients tolerate less antithrombotic intensity than the Caucasian populations on whom dose recommendations were calibrated. Ticagrelor exposure is higher in East-Asian patients, baseline platelet reactivity is lower, and the bleeding-to-ischemia ratio is shifted relative to PLATO-era expectations. Pharmacokinetic and pharmacodynamic work in Chinese and Japanese cohorts has shown that ticagrelor 45 mg twice daily - half the standard maintenance dose - yields platelet inhibition statistically indistinguishable from the 90 mg regimen.

No randomised trial has yet tested an aspirin-free, half-dose ticagrelor monotherapy strategy initiated at the index PCI in CCS patients. The closest registered protocol of which we are aware (NCT07080684) uses ticagrelor 60 mg twice daily following a one-month DAPT lead-in, with a two-arm design. We therefore conducted a three-arm randomised pilot trial in East-Asian CCS patients to compare standard DAPT, DAPT with half-dose ticagrelor, and aspirin-free half-dose ticagrelor monotherapy from the day of PCI, using the change in P2Y₁₂ reaction units (PRU) as the primary pharmacodynamic readout and twelve-month clinical events as exploratory endpoints.

Study Overview

• Status: Completed
• Conditions: Chronic Coronary Syndrome; Coronary Artery Disease; Percutaneous Coronary Intervention
• Intervention / Treatment: Drug: Aspirin 100 mg + clopidogrel (300 mg load → 75 mg daily) ×6 months, then aspirin monotherapy; Drug: Aspirin 100 mg + ticagrelor (90 mg load → 45 mg twice daily) ×6 months, then aspirin monotherapy; Drug: Ticagrelor (90 mg load → 45 mg twice daily) monotherapy; aspirin stopped at day 2 after randomisation; continued indefinitely

Detailed Description

Six months of aspirin plus clopidogrel remains the recommended antiplatelet regimen after percutaneous coronary intervention (PCI) for chronic coronary syndrome (CCS), with the more potent P2Y₁₂ inhibitors reserved for the acute coronary syndromes (ACS) that produced their pivotal evidence. Yet the contemporary landscape of post-PCI antithrombotic therapy has shifted considerably since PLATO and TRITON-TIMI 38, and the conventional algorithm sits increasingly uneasily with two well-established realities. The first is the now consistent demonstration that aspirin contributes more to bleeding than to ischemic protection in patients adequately treated with a P2Y₁₂ inhibitor. TWILIGHT, TICO, T-PASS, ULTIMATE-DAPT and GLOBAL LEADERS have, in sequence, established that withdrawing aspirin after a defined period of P2Y₁₂-based DAPT reduces clinically relevant bleeding without an excess of ischemic events. Each of these trials, however, retained ticagrelor at the standard 90 mg twice-daily dose, required a run-in of conventional DAPT before aspirin was stopped, and enrolled populations dominated by ACS.

The second is the persistent and now mechanistically grounded observation that East-Asian patients tolerate less antithrombotic intensity than the Caucasian populations on whom dose recommendations were calibrated. Ticagrelor exposure is higher in East-Asian patients, baseline platelet reactivity is lower, and the bleeding-to-ischemia ratio is shifted relative to PLATO-era expectations. Pharmacokinetic and pharmacodynamic work in Chinese and Japanese cohorts has shown that ticagrelor 45 mg twice daily - half the standard maintenance dose - yields platelet inhibition statistically indistinguishable from the 90 mg regimen.

No randomised trial has yet tested an aspirin-free, half-dose ticagrelor monotherapy strategy initiated at the index PCI in CCS patients. The closest registered protocol of which we are aware (NCT07080684) uses ticagrelor 60 mg twice daily following a one-month DAPT lead-in, with a two-arm design. We therefore conducted a three-arm randomised pilot trial in East-Asian CCS patients to compare standard DAPT, DAPT with half-dose ticagrelor, and aspirin-free half-dose ticagrelor monotherapy from the day of PCI, using the change in P2Y₁₂ reaction units (PRU) as the primary pharmacodynamic readout and twelve-month clinical events as exploratory endpoints.

Base on above condition, Patients were randomised 1:1:1 by computer-generated sequence. Treatment allocation was open-label; PRU was assayed by laboratory personnel blinded to group. Loading doses were administered after randomisation and before PCI on the following day.

Control (aspirin plus clopidogrel): aspirin 100 mg plus a 300 mg clopidogrel loading dose; then aspirin 100 mg plus clopidogrel 75 mg once daily for six months, followed by aspirin 100 mg monotherapy.

Experimental A (aspirin plus half-dose ticagrelor): aspirin 100 mg plus a 180 mg ticagrelor loading dose; then aspirin 100 mg plus ticagrelor 45 mg twice daily for six months, followed by aspirin 100 mg monotherapy.

Experimental B (half-dose ticagrelor monotherapy): aspirin 100 mg plus a 180 mg ticagrelor loading dose; then ticagrelor 45 mg twice daily monotherapy with aspirin discontinued at day 2 after randomisation, continued indefinitely.

All procedures used contemporary second-generation drug-eluting stents and were performed by experienced operators. Procedural anticoagulation, intracoronary imaging and physiologic assessment were left to operator discretion. Lesion complexity was classified according to the ACC/AHA lesion morphology criteria, and the number of diseased vessels, presence of chronic total occlusion, number of stents, total stent length and use of intravascular imaging (intravascular ultrasound or optical coherence tomography) were recorded for each patient. In patients with multivessel disease, the choice between surgical and percutaneous revascularization followed heart-team evaluation; those who declined coronary artery bypass grafting after detailed explanation and shared decision-making with the patient and family underwent complete percutaneous revascularization, which could increase the number and total length of stents implanted. Statin therapy and other guideline-directed medical therapies were prescribed according to standard care.

Endpoints The primary endpoint was the change in PRU from baseline to follow-up, with follow-up measured approximately two weeks after PCI. Secondary endpoints, all collected over twelve months, were major adverse cardiovascular events (MACE - a composite of all-cause death, target-vessel or target-lesion revascularization, and recurrent myocardial infarction); any clinically relevant bleeding, classified by the Bleeding Academic Research Consortium criteria;15 and study-drug intolerance or crossover, including ticagrelor-related dyspnoea.

Pharmacodynamic assessment Platelet reactivity was assessed with the VerifyNow P2Y₁₂ point-of-care assay on whole-blood samples drawn at two time points: before the index loading dose, and at a median of seventeen days after PCI. Results are expressed in PRU. High platelet reactivity was pre-specified as PRU ≥ 208 and very low reactivity as PRU < 85

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung City, Taiwan, 813414
    • Kaohsiung Veterans General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Key Inclusion Criteria Chronic coronary syndrome; elective PCI; able to give informed consent (per protocol)

Exclusion Criteria:

• ACS at presentation, prior intolerance to any study drug, active bleeding or BARC ≥ 3 bleeding within three months,15 NYHA IV heart failure, platelet count below 100 × 10⁹/L, eGFR below 30 mL/min/1.73 m², severe hepatic dysfunction, planned non-cardiac surgery within twelve months, or inability to provide consent. Patients in whom PCI was not performed at the index procedure (per protocol )

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm 1 (Control); Aspirin 100 mg + clopidogrel (300 mg load → 75 mg daily) ×6 months, then aspirin monotherapy	Drug: Aspirin 100 mg + clopidogrel (300 mg load → 75 mg daily) ×6 months, then aspirin monotherapy; Aspirin 100 mg + clopidogrel (300 mg load → 75 mg daily) ×6 months, then aspirin monotherapy
Experimental: Arm 2 (Experimental A); Aspirin 100 mg + ticagrelor (90 mg load → 45 mg twice daily) ×6 months, then aspirin monotherapy	Drug: Aspirin 100 mg + ticagrelor (90 mg load → 45 mg twice daily) ×6 months, then aspirin monotherapy; Control (aspirin plus clopidogrel): aspirin 100 mg plus a 300 mg clopidogrel loading dose; then aspirin 100 mg plus clopidogrel 75 mg once daily for six months, followed by aspirin 100 mg monotherapy. Experimental A (aspirin plus half-dose ticagrelor): aspirin 100 mg plus a 180 mg ticagrelor loading dose; then aspirin 100 mg plus ticagrelor 45 mg twice daily for six months, followed by aspirin 100 mg monotherapy. Experimental B (half-dose ticagrelor monotherapy): aspirin 100 mg plus a 180 mg ticagrelor loading dose; then ticagrelor 45 mg twice daily monotherapy with aspirin discontinued at day 2 after randomisation, continued indefinitely
Experimental: Arm 3 (Experimental B); Ticagrelor (90 mg load → 45 mg twice daily) monotherapy; aspirin stopped at day 2 after randomisation; continued indefinitely	Drug: Ticagrelor (90 mg load → 45 mg twice daily) monotherapy; aspirin stopped at day 2 after randomisation; continued indefinitely; Ticagrelor (90 mg load → 45 mg twice daily) monotherapy; aspirin stopped at day 2 after randomisation; continued indefinitely

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in P2Y12 reaction units (PRU) from baseline to follow-up (VerifyNow P2Y12 assay)		P2Y12 reaction units (PRU) are follow up before randomization and at 14 days after randomization
Change in P2Y12 reaction units (PRU) from baseline to follow-up (VerifyNow P2Y12 assay)	Platelet reactivity was assessed with the VerifyNow P2Y₁₂ point-of-care assay on whole-blood samples drawn at two time points: before the index loading dose, and at a median of seventeen days after PCI. Results are expressed in PRU. High platelet reactivity was pre-specified as PRU ≥ 208 and very low reactivity as PRU < 85	Enrolled patient from Jan 1, 2024 to Dec 31 2024, and all patient received at 1 year complete follow up

Collaborators and Investigators

• Sponsor: Kaohsiung Veterans General Hospital.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2024
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: May 27, 2026
• First Submitted That Met QC Criteria: May 27, 2026
• First Posted (Actual): June 2, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: chronic coronary syndrome; percutaneous coronary intervention; ticagrelor; dual antiplatelet therapy; P2Y₁₂ reaction units; aspirin-free strategy
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Coronary Artery Disease; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Purines; Phenols; Benzene Derivatives; Nucleosides; Ribonucleosides; Thiophenes; Salicylates; Hydroxybenzoates; Adenosine; Purine Nucleosides; Ticlopidine; Thienopyridines; Ticagrelor; Clopidogrel; Aspirin
• Other Study ID Numbers: KSVGH 23-CT12-07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: started once the result was publicated. for 1 year
• IPD Sharing Access Criteria: The researcher, surveyed by all authors, and if all authors agreed, data will be accessed. they will get the data from Chief Feng Yu Kuo via e-mail
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No