Antiplatelet Therapies in Patients With Depression and Coronary Disease

Study Overview
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Brief Summary
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Depression after an acute coronary syndrome (ACS) but also at any time after CAD diagnosis, is highly associated with death, and it predicts mortality more than any other risk factor, comorbidity or follow-up events, suggesting that the standard medical therapy may not be sufficient to prevent the poor prognosis in these patients. This study aims to assess whether depression might affect the response to dual antiplatelet therapy (DAPT) as recommended in coronary artery disease (CAD) patients. Specific aims: to evaluate whether depression affects the antithrombotic response during Aspirin (ASA) plus clopidogrel (CLP) therapy in CAD patients. to assess the antithrombotic effects of ASA plus ticagrelor or prasugrel (TCG/PSG) therapy in CAD patients with depression by evaluating pro-thrombotic phenotype in CAD patients with and without depression during ASA+TCG/PSG. to assess whether there is or not the reactivation of pro-thrombotic profile after cessation of dual antiplatelet therapy in CAD patients with or without depression in single antiplatelet therapy after TCG/PSG cessation.

Detailed Description
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This study is a multicentre, prospective, observational, case-control, and cross-sectional study. It is planned to enrol 400 patients/subjects (300 patients at Centro Cardiologico Monzino and 100 subjects at IRCCS National Neurological Institute C. Mondino Foundation). Pharmacological treatments in progress will be recorded, administration of Beck Depression Inventory-II (BDI-II), and a fasting blood venous sample (from ante-cubital vein) will be carried out for the haematochemical analyses and for research samples. First morning-urine will be collected for oxidative stress evaluation.

Official Title
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Effect of Antiplatelet Therapies in Patients With Depression and Coronary Disease

Conditions
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Coronary Artery Disease, Depression

Intervention / Treatment
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* Other: standard Aspirin (ASA) + clopidogrel (CLP) therapy
* Other: standard Aspirin (ASA) + Ticagrelor (TCG) or Prasugrel (PSG) therapy
* Other: standard ASA therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Centro Cardiologico Monzino: Patients/subjects of both sexes, aged between 18 and 85 years with or without depression, with CAD: Group 1: CAD patients in ASA+CLP (100mg+75mg/daily) therapy with the absence of acute coronary symptoms for at least 5 months. Group 2: CAD patients in ASA+TCG/PSG (TCG:90mg/b.i.d or PSG:10mg/daily) therapy, at least 6 months after ACS. Group 3: CAD patients during ASA treatment alone at least 1 month after TCG/PSG cessation. IRCCS National Neurological Institute C. Mondino Foundation: Group 1: Patients/subjects of both sexes, aged between 18 and 85 years with or without depression, without CAD. Exclusion Criteria: severe chronic heart failure (NYHA class III/IV) severe concomitant valvular disease infectious pathologies autoimmune diseases haematological diseases serious kidney or liver failure positive anamnesis for current or previous neoplasia in the 5 years prior to enrolment positive anamnesis for major traumas and/or surgery in the 6 months prior to enrolment taking immunosuppressive drugs taking of anti-inflammatory drugs taking of antidepressant drugs presence of dementia and psychiatric disorders other than depression Coronavirus disease-19 (COVID-19) swab positive

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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 |
| --- | --- |
| Group 1a<br>CAD patients with depression on standard ASA+CLP therapy. | Other: standard Aspirin (ASA) + clopidogrel (CLP) therapy<br>* ASA100mg + CLP 75mg daily<br>|
| Group 1b<br>CAD Patients without depression on standard ASA+CLP therapy. | Other: standard Aspirin (ASA) + clopidogrel (CLP) therapy<br>* ASA100mg + CLP 75mg daily<br>|
| Group 2a<br>CAD patients with depression on standard ASA+TCG/PSG therapy. | Other: standard Aspirin (ASA) + Ticagrelor (TCG) or Prasugrel (PSG) therapy<br>* ASA 100 mg + TCG 90mg/b.i.d or PSG10mg daily<br>|
| Group 2b<br>CAD patients without depression on standard ASA+TCG/PSG therapy. | Other: standard Aspirin (ASA) + Ticagrelor (TCG) or Prasugrel (PSG) therapy<br>* ASA 100 mg + TCG 90mg/b.i.d or PSG10mg daily<br>|
| Group 3a<br>CAD patients with depression on standard ASA treatment alone at least 1 month after TCG/PSG cessation. | Other: standard ASA therapy<br>* ASA 100 mg daily<br>|
| Group 3b<br>CAD patients without depression on standard ASA treatment alone at least 1 month after TCG/PSG cessation. | Other: standard ASA therapy<br>* ASA 100 mg daily<br>|
| Group 1c<br>Subjects with depression without CAD (DS) are enrolled are enrolled as a comparison group. | |
| Group 1d<br>Healthy control subjects (HC), subjects without depression and without CAD are enrolled as a comparison group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Verify whether depression affects the platelet response during ASA plus CLP therapy in CAD patients | Measuring platelet activity markers | 3 years | 
| Verify whether depression affects the coagulation during ASA plus CLP therapy in CAD patients | Measuring all the parameters of clot formation and lysis collected by thromboelastography analyses | 3 years | 
| Verify whether depression affects oxidative stress during ASA plus CLP therapy in CAD patients | Measuring lipid peroxidation | 3 years | 
| Assess the effects of ASA plus TCG/PSG therapy on platelet response in CAD patients with depression | Measuring platelet activity markers | 3 years | 
| Assess the effects of ASA plus TCG/PSG therapy on coagulation in CAD patients with depression | Measuring all the parameters of clot formation and lysis collected by thromboelastography analyses | 3 years | 
| Assess the effects of ASA plus TCG/PSG therapy on oxidative stress in CAD patients with depression | Measuring lipid peroxidation | 3 years | 
| Assess whether there is or not the activation of platelet response after cessation of dual antiplatelet therapy in CAD patients with depression | Measuring platelet activity markers | 3 years | 
| Assess whether there is or not the activation of coagulation after cessation of dual antiplatelet therapy in CAD patients with depression | Measuring all the parameters of clot formation and lysis collected by thromboelastography analyses | 3 years | 
| Assess whether there is or not the activation of oxidative stress after cessation of dual antiplatelet therapy in CAD patients with depression | Measuring lipid peroxidation | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CLP metabolism in patients with depression and CAD | Measuring the CLP active metabolite | 3 years | 
| Epigenetic modification in patients with depression and CAD | Through miRNAs analysis | 3 years | 
| DNA methylation in patients with depression and CAD | Measuring DNA methylation levels of two 5'-C-phosphate-G-3' (CpG) dinucleotides on P2Y12 | 3 years | 
| Impact of depression on oxidative stress in patients without CAD | Measuring platelet activity markers | 3 years | 
| Effect of depression on oxidative stress in patients without CAD | Measuring lipid peroxidation | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary Artery Disease, Depression, Acetylsalicylic acid, Prasugrel, Ticagrelor, Dual antiplatelet therapy