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

Overview

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.

Interventions

• Other Cardio-Oncology Referral
  Referral to cardio-oncology for guidelines-based personalized cardio-oncology management
• 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

Primary outcome measures

• Rate of any CV medication Initiation and/or Change [Time frame: 3 Months Post-Intervention]

Secondary outcome measures (12)

• The Rate of Compliance with CV Therapeutic Medication Intervention [Time frame: 6 and 12 Months Post Intervention]
• Rate of Statin Intervetion [Time frame: 3 Months Post Intervention]
• Rate of Compliance with Statin Medication Intervention [Time frame: 6 and 12 Months Post Intervention]
• Rate of any CV Medication Intervention [Time frame: 6 Months Post-Intervention]
• Changes in Biological CV Risk Factor [Time frame: 3, 6, and 12 Month Post-Intervention]
• Changes in Biological CV Risk Factor [Time frame: 3, 6, and 12 Month Post-Intervention]
• Changes in Biological CV Risk Factor [Time frame: 3, 6, and 12 Month Post-Intervention]
• Changes in Biological CV Risk Factor [Time frame: 3, 6, and 12 Month Post-Intervention]
• Rate of Coronary Artery Disease Testing [Time frame: 3, 6, and 12 Month Post-Intervention]
• Rate of new CV or Cardiac Diagnosis [Time frame: 3, 6, and 12 Month Post-Intervention]
• One-Year MACE Rate [Time frame: 12 Months Post-Intervention]
• Rate of Grade ≥ 2 Cardiac CTCAE [Time frame: 12 Month Post-Intervention]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Supportive care

Study locations

United States · 1 center

• Cedars Sinai Medical Center — Los Angeles

Identifiers

NCT: NCT07223385 · IIT2025-09-BALLAS-ATKINS-HEART

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗