Antiplatelet Therapies in Patients With Depression and Coronary Disease (ENHANCE)

Effect of Antiplatelet Therapies in Patients With Depression and Coronary Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Depression; Coronary Artery Disease
• Intervention / Treatment: Other: standard Aspirin (ASA) + clopidogrel (CLP) therapy; Other: standard Aspirin (ASA) + Ticagrelor (TCG) or Prasugrel (PSG) therapy; Other: standard ASA therapy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

• Study Contact: Name: Giancarlo Marenzi, MD; Phone Number: 02.58002582; Email: giancarlo.marenzi@cardiologicomonzino.it
• Study Contact Backup: Name: Silvia Stella Barbieri, PhD; Phone Number: 02.58002021; Email: silvia.barbieri@cardiologicomonzino.it

Study Locations

• Italy
  • Milan, Italy, 20138
    • Recruiting
    • IRCCS Centro Cardiologico Monzino
    • Contact: Giancarlo Marenzi, MD; Phone Number: 02.58002582; Email: giancarlo.marenzi@cardiologicomonzino.it
    • Contact: Silvia Stella Barbieri, PhD; Phone Number: 02.58002021; Email: silvia.barbieri@cardiologicomonzino.it
  • Pavia, Italy, 27100
    • Recruiting
    • IRCCS National Neurological Institute "C. Mondino" Foundation
    • Contact: Giulia Perini, MD; Phone Number: 0382.380343; Email: giulia.perini@mondino.it

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

The population of this study includes patients/subjects with or without depression, with CAD (to be enrolled at Centro Cardiologico Monzino) and without CAD (to be enrolled at IRCCS National Neurological Institute "C. Mondino" Foundation)

Description

Inclusion Criteria:

1. 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.

2. 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

Study Plan

How is the study designed?

Number of groups / cohorts

8

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1a; CAD patients with depression on standard ASA+CLP therapy.	Other: standard Aspirin (ASA) + clopidogrel (CLP) therapy; ASA100mg + CLP 75mg daily
Group 1b; CAD Patients without depression on standard ASA+CLP therapy.	Other: standard Aspirin (ASA) + clopidogrel (CLP) therapy; ASA100mg + CLP 75mg daily
Group 2a; CAD patients with depression on standard ASA+TCG/PSG therapy.	Other: standard Aspirin (ASA) + Ticagrelor (TCG) or Prasugrel (PSG) therapy; ASA 100 mg + TCG 90mg/b.i.d or PSG10mg daily
Group 2b; CAD patients without depression on standard ASA+TCG/PSG therapy.	Other: standard Aspirin (ASA) + Ticagrelor (TCG) or Prasugrel (PSG) therapy; ASA 100 mg + TCG 90mg/b.i.d or PSG10mg daily
Group 3a; CAD patients with depression on standard ASA treatment alone at least 1 month after TCG/PSG cessation.	Other: standard ASA therapy; ASA 100 mg daily
Group 3b; CAD patients without depression on standard ASA treatment alone at least 1 month after TCG/PSG cessation.	Other: standard ASA therapy; ASA 100 mg daily
Group 1c; Subjects with depression without CAD (DS) are enrolled are enrolled as a comparison group.
Group 1d; Healthy control subjects (HC), subjects without depression and without CAD are enrolled as a comparison group.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centro Cardiologico Monzino
• Collaborators: IRCCS National Neurological Institute "C. Mondino" Foundation
• Investigators: Principal Investigator: Giancarlo Marenzi, MD, IRCCS Centro Cardiologico Monzino

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2022
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: March 8, 2023
• First Submitted That Met QC Criteria: April 6, 2023
• First Posted (Actual): April 20, 2023

Study Record Updates

• Last Update Posted (Actual): April 20, 2023
• Last Update Submitted That Met QC Criteria: April 6, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Depression; Ticagrelor; Coronary Artery Disease; Prasugrel; Dual antiplatelet therapy; Acetylsalicylic acid
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Mood Disorders; Arteriosclerosis; Arterial Occlusive Diseases; Depression; Depressive Disorder; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Ticagrelor; Clopidogrel; Prasugrel Hydrochloride
• Other Study ID Numbers: CCM 1422

Drug and device information, study documents

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