High Cardiovascular Risk Intervention With Cardio-Oncology Consultation for Prostate Cancer Following Androgen Receptor Pathway Inhibitor (ARPI) Therapy (Heart-Safe)

In patients with prostate cancer (PC), cardiovascular disease (CVD) causes significant morbidity and is the second leading cause of death. Both pre-existing CVD and the use of androgen deprivation therapy (ADT)-a key cornerstone of treatment for men with locally advanced or metastatic PC1,2 contribute to increased CV risk. ADT has been associated with adverse metabolic effects, including increased central adiposity, elevated low-density lipoprotein (LDL) levels, impaired glycemic control, and arterial wall remodeling and endothelial dysfunction

The data demonstrates that for most patients, the status quo is insufficient6 and there remains a critical gap in the early identification of high CV-risk PC patients who may benefit most from aggressive risk mitigation strategies. Mitigation strategies, like the addition of statins as primary prevention, have shown decrease in MI/CHD death across thousands of patients. Age-related expansion of hematopoietic clones carrying recurrent somatic mutations, termed clonal hematopoiesis of indeterminate potential (CHIP) has recently been identified as a significant driver of atherosclerosis, doubling the risk of coronary heart disease. Notably, while CHIP is detectable in ~10% of persons over 70 years old, it is enriched in patients with solid malignancies, and radiotherapy exposure is among the most decisive risk factors for developing CHIP12-15. The inflammation-related metabolic signals are activated androgen signaling and exacerbated in patients with CHIP. However, the mechanistic link and clinical consequence are less understood. Therefore, it is critical to study the CV impact of CHIP and metabolic perturbations in patients with PC treated with ARSI therapy.

We plan to address these critical gaps by testing our innovative hypothesis that early cardio-oncology intervention with aggressive guidelines-based CV optimization during ARPI therapy will reduce CV risk and that CHIP and metabolomics will help identify adverse metabolic remodeling to improve CV risk prediction.

Robust epidemiological and clinical trial data consistently demonstrate that patients with PC are poorly optimized from a CV risk modification perspective, and existing CV risk models do not perform well in patients with cancer. The data demonstrates that for most patients, the status quo is insufficient and there remains a critical gap in the early identification of high CV-risk PC patients who may benefit most from aggressive risk mitigation strategies.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer (Diagnosis); Prostate Cancer Stage IV; CV Risk
• Intervention / Treatment: Other: Cardio-Oncology Referral; Other: Notification to PCP/General Cardiologist

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trial Recruitment Navigator; Phone Number: 13104232133; Email: GroupCancerTrialInformation@cshs.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
      • Principal Investigator: Leslie Ballas, MD
      • Principal Investigator: Katelyn Atkins, MD, PhD
      • Contact: Clinical Trial Recruitment Navigator; Phone Number: 13104232133; Email: GroupCancerTrialInformation@cshs.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Prostate cancer with localized, very-high risk, lymph-node positive, and/or metastatic (Stage IV) disease.
• Being treated with ARPI therapy with intended duration ≥ 18 months.

• Age > 65 years old and at least one CV risk factor, or age 45-65 years with at least two CV risk factors:

  • Hypertension
  • Hyperlipidemia
  • Diabetes mellitus
  • Family history of early CAD (male first-degree relative (father or brother) with CAD before age 55; female first-degree relative (mother or sister) with CAD before age 65)
  • Presence of coronary artery calcium (CAC) on chest CT imaging
• ECOG 0-2
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.

Exclusion Criteria:

• Prior ARPI therapy exposure > 6 months duration.
• Established care with cardio-oncologist (cardiologist with expertise in CV risks of cancer and cardiotoxic cancer therapies).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cardo-Oncolody Referral; Referral to cardio-oncology for guidelines-based personalized cardio-oncology management	Other: Cardio-Oncology Referral; Referral to cardio-oncology for guidelines-based personalized cardio-oncology management
Active Comparator: PCP/General Cardiology Care; Notification to patient's primary care physician and/or general cardiologist and recommendation for CV risk optimization after initiation of ARPI therapy	Other: Notification to PCP/General Cardiologist; Notification to patient's primary care physician and/or general cardiologist and recommendation for CV risk optimization after initiation of ARPI therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of any CV medication Initiation and/or Change	To evaluate the rate of any CV medication initiation and/or change at 3-months following cardio-oncology consultation versus standard of care. Rate of any CV medication intervention at 3-months (Note: CV medication defined as: lipid-lowering, anti-hypertensive, anti-anginal, anti-platelet, anti-arrhythmic, heart failure medications)	3 Months Post-Intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Rate of Compliance with CV Therapeutic Medication Intervention	To determine the rate of compliance with CV therapeutic medication intervention at 6 and 12 months	6 and 12 Months Post Intervention
Rate of Statin Intervetion	To determine the rate of statin intervention at 3 months	3 Months Post Intervention
Rate of Compliance with Statin Medication Intervention	To determine the rate of compliance with statin medication intervention at 6 and 12 months	6 and 12 Months Post Intervention
Rate of any CV Medication Intervention	To determine the rate of any CV medication intervention at 6 months	6 Months Post-Intervention
Changes in Biological CV Risk Factor	To assess changes in biological CV risk factors (low density lipoprotein [LDL])	3, 6, and 12 Month Post-Intervention
Changes in Biological CV Risk Factor	To assess changes in biological CV risk factors (systolic blood pressure)	3, 6, and 12 Month Post-Intervention
Changes in Biological CV Risk Factor	To assess changes in biological CV risk factors (hemoglobin A1c)	3, 6, and 12 Month Post-Intervention
Changes in Biological CV Risk Factor	To assess changes in biological CV risk factors (body mass index)	3, 6, and 12 Month Post-Intervention
Rate of Coronary Artery Disease Testing	To determine the rate of coronary artery disease (CAD) testing (coronary CT angiograms, CAC scans, stress tests, and invasive coronary angiograms)	3, 6, and 12 Month Post-Intervention
Rate of new CV or Cardiac Diagnosis	To determine the rate of new CV or cardiac diagnosis	3, 6, and 12 Month Post-Intervention
One-Year MACE Rate	To determine the one-year MACE rate	12 Months Post-Intervention
Rate of Grade ≥ 2 Cardiac CTCAE	To determine one-year rate of grade ≥ 2 cardiac common terminology criteria for adverse events (CTCAE)	12 Month Post-Intervention

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Investigators: Principal Investigator: Katelyn Atkins, MD, PhD, Cedars-Sinai Medical Center; Principal Investigator: Leslie Ballas, MD, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): July 1, 2030

Study Registration Dates

• First Submitted: October 29, 2025
• First Submitted That Met QC Criteria: October 30, 2025
• First Posted (Actual): October 31, 2025

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: High-Risk; CV Risk Factors; Lymph-node positive; ARPI Therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Pathological Conditions, Signs and Symptoms; Prostatic Neoplasms; Disease
• Other Study ID Numbers: IIT2025-09-BALLAS-ATKINS-HEART

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