ObseRvation After Acute Coronary Syndrome for deveLopment of trEatment Options (ORACLE)

Exacerbation of Coronary Heart Disease: the Logic and Probabilistic Processes of Flow Prediction for Optimization of Treatment

The aim of the study is developing an individualized risk model for the unfavorable outcomes of coronary artery disease and complications from ongoing therapy, according to clinical, instrumental, biochemical and genetic parameters in patients with acute coronary syndrome.

Inclusion criteria: patients with acute coronary syndrome (with or without ST elevation) who have indications for PCI Number of inclusion patients - 1655 patients Scheduled time of follow up - 24 month Primary end-point: all-cause death Secondary end-points: any cardiovascular events (cardiovascular death, nonfatal myocardial infarction, non-fatal stroke); non-fatal myocardial infarction; recurrent acute coronary syndrome; non-fatal stoke; complicated atherosclerosis; recurrent PCI; bleeding

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome

Detailed Description

The role of genetic factors in the development of coranary heart disease (CHD) exacerbations studied not enough. Most research in this area planned and carried out on a "case-control". Using a similar protocol entails significant errors are associated with a high incidence of subclinical atherosclerotic vascular lesions. Moreover, much of atheroma is extravasal, making it impossible to identify them by angiography. Therefore, necessary to conduct prospective studies to estimate the frequency of so-called hard endpoints. Previously, similar trials were conducted, mainly in connect with drug approving procedures. The spread data from them to other patients directly is not entirely justified. At the same time, the influence of genetic factors in this group of patients can be substantial.

In the previous part of the study, the sample of patients of Moscow, St. Petersburg, Kazan, Chelyabinsk, Stavropol, Perm, and Rostov-on-the-Don was formed, of 1,200 people admitted due to acute coronary syndrome (ACS) including unstable angina and acute myocardial infarction, at coronary care units with follow-up for three years. We found several factors, including genetic, that significantly affect the outcomes of the disease. Coronary atherosclerosis and its complications now considered as a multifactorial disease associated with inherent factors. Therefore, the project provides, besides accounting a significant amount of clinical and instrumental data, the determination of a wide range of genotypes and alleles of polymorphic markers candidate genes encoding the protein factors of the hemostatic system, enzymes of lipid metabolism system, and anti-inflammatory cytokines. It is assumed that the prediction outcomes of coronary heart disease should be carried out taking into account the fact that several factors (gender, diabetes, age, aortic stenosis, atrial fibrillation, etc.) can not only significantly change the forecast itself but also affecting the significance of other risk factors. Since the last study, the standards significantly of ACS management changed. Invasive treatment not only creates opportunities to reduce coronary mortality but also increased demands on the patient's adherence to the assigned medication and creates additional risks associated with its activity (especially with an antithrombotic treatment activity). In these circumstances, the development of personalized approaches to prescribing drugs is particularly important. Thus, the prediction of coronary heart disease outcomes after an ACS on a set of clinical, instrumental, biochemical and genetic indicators is of great importance, as it allows to plan the most optimal treatment for the individual patient.

The aim of the study was to develop a model of individualized risk of coronary heart disease outcomes and side effects of therapy based on clinical and instrumental, biochemical, and genetic parameters in patients with ACS.

• Study Type: Observational
• Enrollment (Actual): 1655

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Study population consists of consistently hospitalized patients with ACS from 4 vascular centers of Moscow, Kazan, Astrakhan and Krasnodar

Description

Inclusion Criteria:

1. Patients with acute coronary syndrome without ST-segment elevation meeting the criteria of a very high, high or intermediate risk, and patients from the low-risk group, if they have episodes of myocardial ischemia in any way Very high risk (1 criterion is sufficient)

   • Pulmonary edema, most probably due to ischemia.
   • The newly appears or increased noise of mitral regurgitation.
   • Rhythm of the gallop, newly developed or intensified wheezing in the lungs.
   • Hypotension against ischemia
   • Ischemia refractory to treatment

   • Persistent ventricular tachycardia or the occurrence of ventricular rhythm disturbances during an attack of ischemia High risk

     (1 criterion is sufficient)

   • An anginal attack more than 20 minutes within the next 48 hours before admission
   • Transitional elevations ST (duration less than 20 min)
   • GRACE score > 140 points
   • Increased cardiospecific markers of necrosis. (you must have at least 2 criteria)
   • Age> 75 years.
   • Angina pectoris with transient changes ST> 0.05 mV.

   Intermediate risk (1 criterion is sufficient)

   • Age> 75 years.
   • Angina pectoris with transient changes ST> 0.05 mV.
   • Inversion of the T wave on ECG (≥ 0.2 mV).
   • GRACE score 104-139 points

   (it is necessary to have at least 2 criteria)

   • Angina of rest (<20 min), stopped spontaneously or with the help of nitroglycerin (NG).
   • Anamnesis of pathology of peripheral or cerebral arteries,
   • Postponed myocardial infarction, including painless, history of revascularization (PCI or CABG)
   • Diabetes.
   • Chronic renal failure (GFR <50 mL / min)

   Low risk All other patients with suspicion of ACS require a survey to identify episodes of ischemia

2. Patients with acute coronary syndrome with ST-segment elevation

   Patients who were hospitalized with symptoms due to acute myocardial infarction (the duration of infarction is no more than 10 days, by the time of hospitalization) and at least one of the following additional criteria identified upon admission to hospital:

   • ST elevation: a persistent ST increase of 1 mm in two adjacent leads from the limbs, or an ST increase of 2 mm in two adjacent thoracic leads
   • the appearance of a new left bundle branch block
   • dynamics of acute myocardial infarction
3. Signed informed consent to participate in the study

Exclusion Criteria:

• Lack of patient consent to participate in the study
• Impossibility of contact with the patient after discharge after index event

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
acute coronary syndrome; All patients should receive standard therapy for acute coronary syndrome and concomitant diseases. All drugs are prescribed according current guidelines and approved indications.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
all-cause death	death from any cause	Number of Participants with end-point during 360 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cardiovascular events	cardiovascular death, non-fatal myocardial infarction, non-fatal stroke	Number of Participants with end-point during 360 days
non-fatal myocardial infarction	non-fatal myocardial infarction	Number of Participants with end-point during 360 days
recurrent acute coronary syndrome	all cases of recurrent myocardial infarction or unstable angina after the index events	Number of Participants with end-point during 360 days
recurrent PCI	all cases of recurrent PCI after the index hospitalization	Number of Participants with end-point during 360 days
complicated atherosclerosis	peripheral atherosclerosis need hospitalisation	Number of Participants with end-point during 360 days
non-fatal stroke	all cases of non-fatal stroke	Number of Participants with end-point during 360 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
bleeding	all cases of bleeding during and after the index hospitalization	Number of Participants with end-point during 360 days

Collaborators and Investigators

• Sponsor: Central State Medical Academy
• Investigators: Principal Investigator: Dmitry A Zateyshchikov, prof, Central State Medical Academy

Publications and helpful links

General Publications

• Brazhnik VA, Minushkina LO, Boeva OI, Khasanov NR, Kosmacheva ED, Chichkova MA, Zateyshchikov DA. Risk Stratification after an Acute Coronary Syndrome: Significance of Antithrombotic Therapy. J Clin Med. 2021 Apr 8;10(8):1572. doi: 10.3390/jcm10081572.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2014
• Primary Completion (Actual): February 20, 2018
• Study Completion (Actual): October 20, 2025

Study Registration Dates

• First Submitted: August 20, 2019
• First Submitted That Met QC Criteria: August 22, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Estimated): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2025
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: coronary artery disease; bleeding; atherosclerosis; gene; death
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Pathological Conditions, Signs and Symptoms; Coronary Artery Disease; Death; Hemorrhage; Atherosclerosis; Acute Coronary Syndrome
• Other Study ID Numbers: ORACLE-II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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