Efficacy and Safety of Low Dose Ticagrelor in Patients With Unstable Angina Pectoris After Coronary Stent Implantation

Study Overview
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Brief Summary
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The study is to evaluate efficacy and safety of low dose of ticagrelor therapy for Chinese unstable angina patients treated with non-urgent coronary stent implantation, to examine whether lower dose ticagrelor (45 mg twice-daily) is not inferior to standard dose (90 mg twice-daily) for the prevention of major adverse cardiovascular and cerebrovascular events, as well as will reduce the incidence of bleeding during long-term treatment.

Detailed Description
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This is a prospective, single center, randomized, parallel-group trial designed to evaluate the efficacy and safety of low dose ticagrelor on a background of aspirin for patients treated with non-urgent coronary stent implantation. 2036 subjects will be enrolled. All patients will receive treatment with aspirin and a P2Y12 inhibitor for 3 months after the index procedure. At 3 months, eligible patients were then randomly assigned in a 1:1 ratio to receive a standard dose ticagrelor 90 mg bid or a lower dose ticagrelor 45 mg bid in addition to aspirin 100mg. The primary efficacy end points are the event rate of the composite of cardiovascular death, non-fatal myocardial infarction, stent thrombosis, coronary revascularization and stroke at 24 months. The primary safety end point is the incidence of PLATO major bleeding at 24 months.

Official Title
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A Prospective, Randomised, Open-labeled, Parallel Group Study to Assess the Efficacy and Safety of Low Dose Ticagrelor Compared With Standard Dose Ticagrelor in Patients With Unstable Angina Pectoris After Drug Eluting Stent Implantation

Conditions
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Unstable Angina Pectoris, Coronary Stent Implantation

Intervention / Treatment
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* Drug: Ticagrelor 90 mg
* Drug: Ticagrelor 45 mg
* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients admission for coronary artery disease treatment with non-emergency percutaneous intervention with stent deployment 18 years≤age≤80 years Patients understands the study requirements and the treatment procedures and provided informed consent before the procedure Exclusion Criteria: Allergy or intolerance to ticagrelor or aspirin Need for oral anticoagulation therapy Concomitant oral or intravenous therapy with strong inhibitors of Cytochrome P450, family 3, subfamily A (CYP3A), Substrates of CYP3A with narrow therapeutic indices or strong inducers of CYP3A Active bleeding, previous history of intracranial hemorrhage, gastrointestinal hemorrhage in the past 6 months and major operation within 30 days High risk of bradyarrhythmias Severe liver dysfunction and abnormal renal function Patient is a woman who is pregnant or nursing Unable or unwilling to give written informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible patients were randomly assigned in a 1:1 ratio to receive ticagrelor 90 mg twice daily plus aspirin 100mg once daily or ticagrelor 45 mg twice daily plus aspirin 100mg once daily.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lower dose ticagrelor<br>Subjects will be treated with ticagrelor 45 mg twice daily in combination with aspirin 100mg once daily. | Drug: Ticagrelor 45 mg<br>* Ticagrelor (AZD6140) 45 mg twice daily dose<br>* Other names: AZD6140;Drug: Aspirin<br>* Aspirin 100 mg once daily dose<br>|
| Active Comparator: Standard dose ticagrelor<br>Subjects will be treated with ticagrelor 90 mg twice daily in combination with aspirin 100mg once daily. | Drug: Ticagrelor 90 mg<br>* Ticagrelor (AZD6140) 90 mg twice daily dose<br>* Other names: AZD6140;Drug: Aspirin<br>* Aspirin 100 mg once daily dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) and major bleeding event | Participants with death from vascular causes, non-fatal myocardial infarction, stent thrombosis, coronary revascularization and stroke. Intention to treat (ITT) analysis of whole population. Events were adjudicated by an endpoint committee. Participants with PLATO major bleeding event including fatal bleeding, intracranial bleeding, intrapericardial bleeding with cardiac tamponade, hypovolemic shock or severe hypotension due to bleeding and requiring pressures or surgery, a decline in the hemoglobin level of 5.0 g per deciliter or more, or the need for transfusion of at least. Events were adjudicated by an endpoint committee. | Randomization up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Any event from the composite of cardiovascular death, non-fatal myocardial infarction, stent thrombosis, coronary revascularization and stroke | Participants with any event from the composite of cardiovascular death, non-fatal MI, stent thrombosis, coronary revascularization and stroke. ITT analysis of intent for invasive management population. Events were adjudicated by an endpoint committee. | Randomization up to 24 months | 
| All cause death | Participants with all cause death. ITT analysis of whole population. Events were adjudicated by an endpoint committee. | Randomization up to 24 months | 
| PLATO-defined any bleeding event | Participants with any other bleeding events (minor bleeding or minimal bleeding) as defined by the PLATO. Events were adjudicated by an endpoint committee. | Randomization up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unstable Angina, Stent, Ticagrelor, Platelet aggregation, Percutaneous Coronary Intervention, Coronary Artery Disease, Major Adverse Cardiovascular and Cerebrovascular Events, Bleeding Events