Atherosclerosis in Chemotherapy-related Cardiotoxicity (ANTEC)

Prognostic Significance of the Atherosclerosis in the Coronary Arteries Assessed in Computed Tomography on the Cardiotoxicity Development After Oncological Treatment

Cardiological complications of oncological treatment, including the most serious of them cardiotoxicity and heart failure, constitute a significant and still unsolved clinical problem. A history of hypercholesterolaemia and coronary artery disease in cancer patients, is one of the risk factors for cardiotoxicity. In recent years, a protective effect of statin treatment on the development of heart failure in cancer patients has been observed. ANTEC (Atherosclerosis iN chemoTherapy-rElated Cardiotoxicity) is a prospective observational study aimed at assessing the impact of the advancement of atherosclerotic lesions in the coronary arteries assessed in computed tomography on the development of left ventricular systolic dysfunction in cancer patients at high risk of myocardial damage. A group of 80 patients diagnosed with cancer before starting high-dose anthracycline chemotherapy (doxorubicin ≥ 240 mg / m2 or epirubicin ≥ 600 mg / m2 body weight), without a history of heart failure and coronary artery disease, will be included in the study. The total follow-up of patients was planned for 12 months. The primary endpoint is time to onset of left ventricular systolic dysfunction as assessed by echocardiography. The secondary composite endpoints include all-cause death, cardiovascular death, myocardial infarction, and stroke. Additionally, the assessment will include: the severity of atherosclerotic changes in the coronary arteries and the calcification index in computed tomography, the percentage decrease in left ventricular ejection fraction, GLS (global longitudinal strain) in echocardiography, and changes in the concentration of biomarkers involved in inflammatory and atherosclerotic processes. This is the first study of this type, which we hope will contribute to a better understanding of the pathophysiology of cardiotoxicity development and to changing the standards of management of oncological patients and improving survival in this group of patients.

Study Overview

• Status: Completed
• Conditions: Atherosclerosis; Cardiotoxicity
• Intervention / Treatment: Diagnostic test: echocardiography, computed tomography

Detailed Description

Cardiological complications of oncological treatment, including the most serious: cardiotoxicity and heart failure, remains the most dangerous cardiological complication of oncological treatment and are still unsolved clinical problem. The fear of the toxic effects of anti-cancer drugs may lead to the modification or abandonment of oncological treatment, and consequently shorten the survival time of cancer patients.

A history of hypercholesterolaemia and coronary artery disease in cancer patients, is one of the risk factors for cardiotoxicity. In recent years, a protective effect of statin treatment on the development of heart failure in cancer patients has been observed. ANTEC (Atherosclerosis iN chemoTherapy-rElated Cardiotoxicity) is a prospective observational study aimed at assessing the impact of the advancement of atherosclerotic lesions in the coronary arteries assessed in computed tomography on the development of left ventricular systolic dysfunction in cancer patients at high risk of myocardial damage. A group of 80 patients diagnosed with cancer before starting high-dose anthracycline chemotherapy (doxorubicin ≥ 240 mg / m2 or epirubicin ≥ 600 mg / m2 body weight), without a history of heart failure and coronary artery disease, will be included in the study. The total follow-up of patients was planned for 12 months. The primary endpoint is time to onset of left ventricular systolic dysfunction as assessed by echocardiography. The secondary composite endpoints include all-cause death, cardiovascular death, myocardial infarction, and stroke. Additionally, the assessment will include: the severity of atherosclerotic changes in the coronary arteries and the calcification index in computed tomography, the percentage decrease in left ventricular ejection fraction, GLS (global longitudinal strain) in echocardiography, and changes in the concentration of biomarkers involved in inflammatory and atherosclerotic processes. This is the first study of this type, which we hope will contribute to a better understanding of the pathophysiology of cardiotoxicity development and to changing the standards of management of oncological patients and improving survival in this group of patients.

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• Poland
  • Warsaw, Poland
    • National Institute of Oncology

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

The study will include patients with diagnosed cancer, diagnosed and qualified for further systemic treatment at the National Institute of Oncology in Warsaw. Patients must give informed and voluntary consent to participate in the study and meet all the conditions for inclusion in the study

The size of the study group was calculated at 80 people. The estimated group size is based on the Cochran-Armitage test for the existence of a trend for a variable on an ordinal scale. The one-sided test was taken into account (alternative hypothesis - increase in the incidence of cardiotoxicity with the severity of atherosclerotic lesions versus null hypothesis - no effect). Assumptions: power - 80%, level of statistical significance - 0.05, one-tailed test for the presence of a trend.

Description

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status from 0 to 2.
2. Age ≥18 years at the time of signing the informed consent.
3. Known neoplastic disease prior to the initiation of chemotherapy with a high dose of anthracyclines (doxorubicin ≥ 240 mg / m2 b.w. or epirubicin ≥ 600 mg / m2 b.w.)
4. No history of heart failure (left ventricular ejection fraction ≥ 50% as assessed by echocardiography).
5. No history of: coronary artery disease, stroke and lower limb atherosclerosis
6. At least moderate baseline cardiovascular toxicity risk according to Heart Failure Association-International Cardio-Oncology Society stratification

Exclusion Criteria:

1. History of heart failure
2. Left ventricle systolic dysfunction with LVEF <50%
3. Significant valve defect
4. Previous chemotherapy or radiation to the chest
5. Presence of any disease with a life expectancy <1 year in the opinion of the investigator.
6. Drug or alcohol abuse
7. Lack of possibility or contraindications for coronary tomography before starting chemotherapy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients with left ventricular systolic dysfunction	echocardiography	from date of randomization until the end of study, up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the secondary composite endpoint: all-cause death, cardiovascular death, myocardial infarction, and stroke	medical records	from date of randomization until the end of study, up to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The presence of atherosclerosis in the coronary arteries and the calcification index	computed tomography	from date of randomization until the end of study, up to 12 months
Percentage decrease in left ventricular ejection fraction, GLS (global longitudinal strain) and MWI (myocardial work index)	echocardiography	from date of randomization until the end of study, up to 12 months
Changes in the concentration of biomarkers involved in inflammatory and proatherosclerotic processes (IL-6, MPO i TNF-alfa).	blood samples	from date of randomization until the end of study, up to 12 months

Collaborators and Investigators

• Sponsor: Maria Sklodowska-Curie National Research Institute of Oncology
• Collaborators: Servier; Polish Cardiac Society

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Actual): September 15, 2024
• Study Completion (Actual): March 15, 2025

Study Registration Dates

• First Submitted: October 26, 2021
• First Submitted That Met QC Criteria: November 8, 2021
• First Posted (Actual): November 11, 2021

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 19, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Heart Diseases; Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Arteriosclerosis; Arterial Occlusive Diseases; Cardiotoxicity; Atherosclerosis
• Other Study ID Numbers: 80/2021

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
• product manufactured in and exported from the U.S.: No