Development of a Risk Prediction Algorithm Through the Investigation of Genetic Risk Factors and the Complexity of Coronary Artery Disease to Estimate Future Risk of Cardiovascular Events: Angiographic (SYNTAX Score), Clinical and Pharmacogenetic Analysis.

• Conditions: Coronary Artery Disease
• Interventions: Genetic: SNPs associated with CAD, SNPs associated with pharmacological response to clopidogrel and statins

• Registration Number: NCT03150680
• Lead Sponsor: AHEPA University Hospital

Brief Summary

The purpose of the research project is to investigate the potential association of 207 genetic polymorphisms with the complexity and the severity of coronary artery disease (SYNTAX score), along with the patients' response to clopidogrel and statin therapy. The aim of the study is to combine genetic, pharmacogenetic, clinical and laboratory data in order to create an algorithm (GEnetic Syntax Score-GESS) that will enable an individualized therapeutic patient approach.

Detailed Description

Regarding Greece, this is the first prospectively enrolling medical database of this magnitude. Clinical and genetic patient information are systematically collected in a fashion that will enable also future retrospective evaluation of clinical and genetic details from each patient. This study is a discrete arm of a series of research projects that focus on the development of personalized medical therapy and share a common purpose: predicting future risk of cardiovascular events, assessing the severity and complexity of coronary artery disease by incorporating genetic information into the SYNTAX score and providing personalized therapeutic guidance to patients. The ultimate goal of the study would be to identify, design and develop a panel of genetic markers that in combination with clinical and angiographic information will be a reliable tool for predicting cardiovascular risk for future adverse events.

Study Timeline

• Study First Submitted: 2017-05-09
• Study First Submitted QC: 2017-05-11
• Study First Posted: 2017-05-12
• Status Verified: 2017-09
• Study Start: 2017-09-01
• Last Update Submitted: 2017-09-06
• Last Update Posted: 2017-09-07
• Primary Completion: 2020-02
• Study Completion: 2020-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1080

Inclusion Criteria

1. Patients giving voluntary written consent to participate in the study
2. Male or female patients between 18 years to 90 years at entry
3. Patients without previous history of CAD
4. Patients who are admitted in the Department of Cardiology in the AHEPA University General Hospital of Thessaloniki and undergo coronary angiography for clinical purposes

Exclusion Criteria

1. Patients < 18 years old and > 90 years old at time of coronary angiography
2. Patients with a previous history of CAD
3. Cardiac Arrest at admission
4. Patients with serious concurrent disease and life expectancy of < 1 year
5. Patients who refuse to give written consent for participation in the study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
SYNTAX score = 0	SNPs associated with CAD, SNPs associated with pharmacological response to clopidogrel and statins	Patients with nonobstructive CAD (≤50 % diameter stenosis)
0 < SYNTAX score <23	SNPs associated with CAD, SNPs associated with pharmacological response to clopidogrel and statins	Low SYNTAX group
SYNTAX score >= 23	SNPs associated with CAD, SNPs associated with pharmacological response to clopidogrel and statins	Intermediate-High SYNTAX group

Primary Outcome Measures

Name	Time	Method
Relationship between genetic risk variants and the SYNTAX score	12 months	All-comers population

Secondary Outcome Measures

Name	Time	Method
MACCEs	12 months	Cardiovascular death, myocardial infarction, stent thrombosis, any re-intervention and stroke
Predictive value of combining a Genetic Risk Score, SYNTAX score and clinical variables for the prediction of 1-year MACCEs	12 months	A multilocus Genetic Risk Score will be calculated as the weighted sum of alleles of 207 single nucleotide polymorphisms previously associated with CAD \[The investigators will construct a multilocus genetic risk score for each individual by summing the number of risk alleles (0/1/2) for each of the 207 SNPs weighted by their estimated effect sizes\].; SYNTAX score is a coronary lesion complexity scoring system and represented by a single number.; Clinical variables include: 1. Major CV risk factors as defined according to ESC Guidelines \[as dichotomous variables-yes or no\]; 2. Ankle-Brachial Index: a tool for diagnosing peripheral artery disease but also an indicator of systemic atherosclerosis \[measurement according to ESC Guidelines-represented by a single number\]; 3. Left Ventricular Ejection Fraction (LVEF%) using echocardiography.
Any BARC (Bleeding Academic Research Consortium) bleeding	12 months	Bleeding Academic Research Consortium (BARC) recently proposed a novel standardized bleeding definition

Trial Locations

Locations (1)

AHEPA University Hospital; 🇬🇷 Thessaloníki, Greece