Brazilian Coronary ARtery Disease

Coronary Artery Disease Clinical Trial

— BARD  

Official title:

The Brazilian Coronary Disease Cohort

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05392491
• Other study ID #: BARD Study
• Status: Not yet recruiting
• Start date: June 1, 2022
• Est. completion date: November 1, 2024

Study information

• Verified date: May 2022
• Source: University of Sao Paulo General Hospital
• Contact: Vinícius Quintão, MD
• Phone: 55 11 2661-5795
• Email: vinicius.quintao[@]hc.fm.usp.br
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Although coronary artery disease may have a stable chronic clinical course, it is known that this reality does not apply to atherosclerotic plaques, they can grow, complicate, stabilize and again start new cycles of growth/destabilization/stabilization or quiescence in the presence or absence of symptoms. While in obstructive coronary lesions there are well-founded guidelines based on multiple clinical studies, in relation to investigation and treatment; on the other hand, in non-obstructive lesions, there are no such guidelines. There are gaps in the knowledge about the prognostic implications of minor injuries and the occurrence of events. This study seeks precisely to fill these knowledge gaps. Of particular relevance are the large number of patients (approximately 10,000 patients) and the long clinical follow-up, that is, in five years.

Description:

Introduction:

For decades, patients with obstructive coronary disease, specifically with lesions above 70%, have been the subject of numerous randomized studies and meta-analyses concerning the influence of drug treatments, revascularization (surgical or percutaneous), and lifestyle on their prognosis. In this scenario, the investigators already have a reasonable knowledge of the behaviors most appropriate for both avoiding events and alleviating symptoms. However, one particular subgroup consists of patients whose lesions are non-obstructive. In most cases, these are considered lesions of ≤70%. Many individuals presented obstructive lesions that were deemed appropriate for angioplasty within this classification. For example, in the study Defer of 325 patients with indications of ischemia, 44.3% presented FFR (fractional flow reserve) ≤0.75, which suggested significant obstruction, and were submitted to ATC. Thus, the investigators consider the threshold ≤70% inappropriate since it includes many patients with ischemia when assessed by FFR.

Therefore, this study has decided to investigate patients with lesions of ≤50% on the supposition that they do not have obstructive lesions.

In addition, although coronary disease may follow a stable clinical course, this is not the case with atherosclerotic plaques. These can grow, become complex, stabilize and reinitiate new cycles of growth/destabilization/stabilization or inactivity, in either the presence or absence of evident symptoms. Though aware of this dynamic, studies were performed to "photograph" at a given time subclinical atherosclerotic load and correlate it to the incidence of the events. The indicators most used for evaluating atherosclerotic load have been the presence of extra-cardiac atherosclerosis (carotid ultrasound) and calcification of the coronary arteries.

Furthermore, the calcium score has been used for the same purpose in the Brazilian population: but only as a prognostic indicator among carriers of family hypercholesterolemia.

However, there are considerable doubts concerning therapeutic interventions in asymptomatic patients with no critical stenosis.

Given this gap, chiefly among the Brazilian population, and being an institution with one of the highest volumes of medical care and screening for coronary disease globally, the investigators have all the necessary conditions to put this important public health problem into perspective.

Objectives:

To evaluate clinical evolution, in five years, of patients with no coronary lesions or lesions <50%, invasive coronary angiography (ICA) exams or coronary angiotomography is performed for the diagnosis of coronary disease.

Population:

Patients were referred to Instituto do Coração (InCor HCFMUSP) for ICA or angiotomography for diagnosis of coronary heart disease from January 1, 2011, to December 31, 2017.

Exclusion criteria: age under 18 years or over 80 years at the time of examination, previous history of an acute coronary syndrome (infarction and unstable angina), revascularization interventions (surgical or percutaneous), valvular heart disease, cardiomyopathies, or diseases with a poor prognosis (expected survival of fewer than five years).

The cohort will be composed of 3 groups: the control group (without coronary lesions), lesion group <30%, and lesion group >30% to <50%.

Study type: an observational, retrospective, with data from the database of InCor, (Heart Institute - InCor, University of São Paulo).

Outcomes: primary composite (general death, acute myocardial infarction, cerebrovascular accident, need for revascularization); secondary outcomes: the isolated components of the primary outcome at five years.

Data to be collected:

1. Age (on the date of examination), gender, presence of risk factors - arterial hypertension (BP >130/85; or use of antihypertensive medication), diabetes mellitus (fasting glucose ≥126 mg/dL, casual >140 mg/dL or GTT >200 mg/dL, or use of oral or injectable hypoglycemic agents), dyslipidemia (LDL >130 mg/dL, triglycerides >150 mg), lipid levels (total cholesterol, HDL-C, LDL-C, and triglycerides); tobacco user (never, ex-tobacco user, active), obesity, exercise, family history, creatinine, chronic kidney disease (glomerular filtration <60 mL/1.73m²/min).

2. Medications in use: ACE inhibitors/ARB; statins; AAS; Beta-blockers and calcium channel antagonists, and diuretics.

3. Clinical status: angina and/or dyspnea.

4. Left ventricular systolic function: normal left ventricular ejection fraction (LVEF) (50%), mild decrease (≥45% to <50%); moderate (>35% to 45%) and severe (<35%).

5. Cardiovascular history: cerebrovascular accident or peripheral arterial disease.

6. Atherosclerotic load:

1. Higher percentage of obstruction of the lumen by comparing the diameter in the lesion region with its proximal neighborhood: absent (0%), very mild (1-30%), and mild (30-49%), for eligibility of each group studied;

2. Total lesion score: zero for absence, 1 for minor injuries(<30%), and 2 for minor injuries(30-50%). Multiplied by their frequency and totaled at the end;

3. The atherosclerotic load will be weighted using the Syntax scores for its location, though the lesions are less than 50%. Left coronary trunk = 5; proximal AD = 3.5; medial AD = 1.5; distal AD = 1; diagonal = 1; proximal circumflex = 1.5; distal = 1; marginal = 1; proximal or distal right coronary artery = 1 and posterior descending artery = 1; coronary calcium score (CAC).

Population:

Patients underwent invasive coronary angiography (ICA) or coronary computed tomography angiography at InCor from January 2011 to December 2014. To allow 5-year follow-up (FU) of all cases. The investigators estimate the inclusion of approximately 5,000 patients, with a minimum of 1,500 in the control group.

Deadlines for execution and analysis:

The investigators anticipate including an average of 40 patients per day and completion at the end of 2 years.

The rate of scheduled events should not exceed 0.5% to 1% per year, so the investigators plan interim analyses at two years FU when the investigators would have at least 600 events for analysis.

Clinical, laboratory, and image data:

Electronic Patient Care System SI3 of InCor will be used to screen and follow the patients. Patients who have not been followed regularly at ambulatory clinics of InCor will be contacted by phone or e-mail to ascertain their evolution. In cases of death, family members or attending physicians will be contacted. Death certificates will be analyzed to adjudicate death´s causes.

Eventually, the Foundation for the State System of Data Analysis (SEADE) database from Estado de São Paulo will be used.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10000
• Est. completion date: November 1, 2024
• Est. primary completion date: May 1, 2024
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients referred to Instituto do Coração (InCor HC, FM-USP) for invasive coronary angiography or angiotomography.

Exclusion Criteria:

• Age under 18 years or over 80 years at the time of examination;

• Previous history of acute coronary syndrome (infarction and unstable angina);

• Revascularization interventions (surgical or percutaneous);

• Valvular heart disease;

• Cardiomyopathies;

• Diseases with a poor prognosis (expected survival of less than 5 years).

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Other:
• No intervention
No intervention. It is an observational study

Locations

Country	Name	City	State
Brazil	Instituto do Coração InCor, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital

Country where clinical trial is conducted

Brazil, 

References & Publications (10)

Ahmadi A, Argulian E, Leipsic J, Newby DE, Narula J. From Subclinical Atherosclerosis to Plaque Progression and Acute Coronary Events: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019 Sep 24;74(12):1608-1617. doi: 10.1016/j.jacc.2019.08.012. Review. — View Citation

Bech GJ, De Bruyne B, Pijls NH, de Muinck ED, Hoorntje JC, Escaned J, Stella PR, Boersma E, Bartunek J, Koolen JJ, Wijns W. Fractional flow reserve to determine the appropriateness of angioplasty in moderate coronary stenosis: a randomized trial. Circulation. 2001 Jun 19;103(24):2928-34. — View Citation

Fernández-Friera L, Peñalvo JL, Fernández-Ortiz A, Ibañez B, López-Melgar B, Laclaustra M, Oliva B, Mocoroa A, Mendiguren J, Martínez de Vega V, García L, Molina J, Sánchez-González J, Guzmán G, Alonso-Farto JC, Guallar E, Civeira F, Sillesen H, Pocock S, Ordovás JM, Sanz G, Jiménez-Borreguero LJ, Fuster V. Prevalence, Vascular Distribution, and Multiterritorial Extent of Subclinical Atherosclerosis in a Middle-Aged Cohort: The PESA (Progression of Early Subclinical Atherosclerosis) Study. Circulation. 2015 Jun 16;131(24):2104-13. doi: 10.1161/CIRCULATIONAHA.114.014310. Epub 2015 Apr 16. — View Citation

Gorgulho B, Alves MA, Teixeira JA, Santos RO, de Matos SA, Bittencourt MS, Benseñor I, Lotufo P, Marchioni DM. Dietary patterns associated with subclinical atherosclerosis: a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) study. Public Health Nutr. 2021 Oct;24(15):5006-5014. doi: 10.1017/S1368980020005340. Epub 2021 Jan 8. — View Citation

Maddox TM, Stanislawski MA, Grunwald GK, Bradley SM, Ho PM, Tsai TT, Patel MR, Sandhu A, Valle J, Magid DJ, Leon B, Bhatt DL, Fihn SD, Rumsfeld JS. Nonobstructive coronary artery disease and risk of myocardial infarction. JAMA. 2014 Nov 5;312(17):1754-63. doi: 10.1001/jama.2014.14681. — View Citation

Makarovic Z, Makarovic S, Bilic-Curcic I, Mihaljevic I, Mlinarevic D. NONOBSTRUCTIVE CORONARY ARTERY DISEASE - CLINICAL RELEVANCE, DIAGNOSIS, MANAGEMENT AND PROPOSAL OF NEW PATHOPHYSIOLOGICAL CLASSIFICATION. Acta Clin Croat. 2018 Sep;57(3):528-541. doi: 10.20471/acc.2018.57.03.17. Review. — View Citation

McClelland RL, Jorgensen NW, Budoff M, Blaha MJ, Post WS, Kronmal RA, Bild DE, Shea S, Liu K, Watson KE, Folsom AR, Khera A, Ayers C, Mahabadi AA, Lehmann N, Jöckel KH, Moebus S, Carr JJ, Erbel R, Burke GL. 10-Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) With Validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study). J Am Coll Cardiol. 2015 Oct 13;66(15):1643-53. doi: 10.1016/j.jacc.2015.08.035. — View Citation

Miname MH, Bittencourt MS, Moraes SR, Alves RIM, Silva PRS, Jannes CE, Pereira AC, Krieger JE, Nasir K, Santos RD. Coronary Artery Calcium and Cardiovascular Events in Patients With Familial Hypercholesterolemia Receiving Standard Lipid-Lowering Therapy. JACC Cardiovasc Imaging. 2019 Sep;12(9):1797-1804. doi: 10.1016/j.jcmg.2018.09.019. Epub 2018 Nov 15. — View Citation

Östgren CJ, Söderberg S, Festin K, Angerås O, Bergström G, Blomberg A, Brandberg J, Cederlund K, Eliasson M, Engström G, Erlinge D, Fagman E, Hagström E, Lind L, Mannila M, Nilsson U, Oldgren J, Ostenfeld E, Persson A, Persson J, Persson M, Rosengren A, Sundström J, Swahn E, Engvall JE, Jernberg T. Systematic Coronary Risk Evaluation estimated risk and prevalent subclinical atherosclerosis in coronary and carotid arteries: A population-based cohort analysis from the Swedish Cardiopulmonary Bioimage Study. Eur J Prev Cardiol. 2021 Apr 23;28(3):250-259. doi: 10.1177/2047487320909300. Epub 2020 Mar 3. — View Citation

Pagidipati NJ, Peterson ED. Should Cardiovascular Preventive Therapy Be Over-the-Counter? J Am Coll Cardiol. 2021 Sep 14;78(11):1124-1126. doi: 10.1016/j.jacc.2021.07.020. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Composite Outcome	Participants presenting the following outcomes: death of any cause, acute myocardial infarction, stroke, and need for revascularization.	5 years
Secondary	Number of participants with acute myocardial infarction	According to classical definition: clinical, electrocardiography and enzymes	5 years
Secondary	Number of participants with stroke	Loss of consciousness and hemiplegia	5 years
Secondary	Number of participants needing revascularization	Coronaries bypass surgery or angioplasty	5 years