Cardiac biomarkers in patients with prostate cancer and cardiovascular disease receiving gonadotrophin releasing hormone agonist vs antagonist

Abstract

Background Gonadotrophin releasing hormone (GnRH) agonists and antagonists reduce testosterone levels for the treatment of advanced and metastatic prostate cancer. Androgen deprivation therapy (ADT) is associated with increased risk of cardiovascular (CV) events and CV disease (CVD), especially in patients with preexisting CVD treated with GnRH agonists. Here, we investigated the potential relationship between serum levels of the cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NTproBNP), D-dimer, C-reactive protein (CRP), and high-sensitivity troponin (hsTn) and the risk of new CV events in prostate cancer patients with a history of CVD receiving a GnRH agonist or antagonist. Methods Post-hoc analyses were performed of a phase II randomized study that prospectively assessed CV events in patients with prostate cancer and preexisting CVD, receiving GnRH agonist or antagonist. Cox proportional hazards models were used to determine whether the selected biomarkers had any predictive effect on CV events at baseline and across a 12month treatment period. Results Baseline and disease characteristics of the 80 patients who took part in the study were well balanced between treatment arms. Ischemic heart disease (66%) and myocardial infarction (37%) were the most common prior CVD and the majority (92%) of patients received CV medication. We found that high levels of NTproBNP (p = 0.008), and hsTn (p = 0.004) at baseline were associated with the development of new CV events in the GnRH agonist group but not in the antagonist. In addition, a nonsignificant trend was observed between higher levels of NTproBNP over time and the development of new CV events in the GnRH agonist group. Conclusions The use of cardiac biomarkers may be worthy of further study as tools in the prediction of CV risk in prostate cancer patients receiving ADT. Analysis was limited by the small sample size; larger studies are required to validate biomarker use to predict CV events among patients receiving ADT.

Role of Cardiac Biomarkers in Cancer Patients

“…High NT-proBNP and troponin baseline levels were associated with the occurrence of new cardiovascular events in the GnRH agonist group but not in the antagonist. There were no significant changes in NT-proBNP and troponin from baseline either in patients who experienced a new cardiovascular event, or in those who did not, during the 12-month follow-up [77,79].…”

Association between medical androgen deprivation therapy and long‐term cardiovascular disease and all‐cause mortality in nonmetastatic prostate cancer

“…34,[45][46][47][48] In one post hoc analysis, the cardiac biomarker N-terminal pro-B-type natriuretic peptide (NTproBNP) at baseline was associated with increased risk of developing cardiovascular events in the LHRH agonist treatment arm but not the antagonist group. 49 These findings need further investigation but could offer a biomarker for clinicians to identify patients more suitable for treatment with an LHRH antagonist. Results are currently awaited from the PRO-NOUNCE trial, a large randomised trial of 545 people evaluating major cardiovascular events between LHRH agonist vs antagonist treated patients.…”

Assessment and Mitigation of Cardiovascular Risk for Prostate Cancer Patients: A Review of the Evidence

“…After 12 months, 8 (20%) patients randomized to GnRH agonist had a MACCE compared to 1 (3%) treated with the antagonist (ARR = 18.1% (95% CI 4.6–31.2), NNT = 6) [ 13 ]. High levels of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and high-sensitivity troponin (hsTn) at baseline were associated with the development of new CV events in the agonist group but not in the antagonist group [ 18 ]. This study is limited due to the small sample size and the suitability of the primary endpoint which was not met.…”