Impact of Evolocumab on the Antiplatelet Effects of Ticagrelor and Aspirin in Patients With Acute Coronary Syndrome

Study Overview
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Brief Summary
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The aim of the present study is to investigate the effects of evolocumab in addition to statin therapy on platelet reactivity in patients with acute coronary syndrome (ACS) while on Ticagrelor and Aspirin treatment.

Detailed Description
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Ticagrelor is a commercially available antiplatelet adenosine diphosphate (ADP) antagonists. They exert their antiplatelet effects by binding to P2Y12 receptors on the platelet surface. Ticagrelor is used in combination with aspirin to prevent and treat thrombosis in patients with acute coronary syndrome, particularly after stent implantation. Aspirin has an established role in the treatment of ACS and secondary prevention of ischaemic heart disease. Aspirin inhibits cyclo-oxygenase (COX) enzymes by irreversible acetylation to block platelet aggregation. Evolocumab is a monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9). The use of evolocumab significantly reduced the incidence of cardiovascular events compared to statins alone. Whether the reduction in cardiovascular events is due to LDL reduction or other mechanisms is currently unclear.

Official Title
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Impact of Evolocumab on the Antiplatelet Effects of Ticagrelor and Aspirin in Patients With Acute Coronary Syndrome

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Evolocumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients were diagnosed as acute coronary disease On therapy with Ticagrelor(90mg bid) and Aspirin(100mg qd), for at least 5 days. Fasting LDL-cholesterol ≥70 mg/dL or a non-high-density lipoprotein cholesterol (HDL-C) of ≥100 mg/dL after ≥4 weeks of optimized stable lipid-lowering therapy with maximally tolerated dose of statin. Have not used Evolocumab in 30 days. Exclusion Criteria: On treatment with any oral anticoagulant. On treatment with any antiplatelet agent other than Aspirin and Ticagrelor in the past 5 days. Creatinine clearance <30 mL/minute. Known severe hepatic impairment. History of a serious hypersensitivity reaction to evolocumab Hemodynamic instability Pregnant and breastfeeding women.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| pro-Evo<br>Patients regularly take Ticagrelor and Aspirin for five days.Platelet activity was test before inject Evolocumab. | |
| 24h-Evo<br>Patients regularly take Ticagrelor and Aspirin for five days, then inject Evolocumab 140mg. Platelet activity was test 24h after inject. | Drug: Evolocumab<br>* evolocumab 140mg subcutaneous injection after regular take Ticagrelor and Aspirin for 5 days.<br>|
| 1w-Evo<br>Patients regularly take Ticagrelor and Aspirin for five days, then inject Evolocumab 140mg. Platelet activity was test 1 week after inject. | Drug: Evolocumab<br>* evolocumab 140mg subcutaneous injection after regular take Ticagrelor and Aspirin for 5 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet Reactivity Defined by VerifyNow PU in Patients diagnosed ACS | The primary end point of our study is the comparison of P2Y12 reaction units (PU) measured by VerifyNow in patients before use evolocumab and 24hours after injected and 1week after injected. PU is well-established measures of platelet reactivity and aggregation in response to antiplatelet medications. The higher is the PU the lower is the effect of the antiplatelet medication. Validity is defined as PU<208. | 1 week | 
| Platelet Reactivity Defined by VerifyNow AU in Patients diagnosed ACS | The second end point of our study is the comparison of COX-1 reaction units(AU) measured by VerifyNow in patients before use evolocumab and 24hours after injected and 1week after injected. AU is well-established measures of platelet reactivity and aggregation in response to antiplatelet medications. The higher is the AU the lower is the effect of the antiplatelet medication. Validity is defined as AU<550. | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Evolocumab, Antiplatelet, Acute Coronary Syndrome