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

Prostate Cancer and Prostatic Diseases volumeĀ 24,Ā pages 177ā€“185 (2021)Cite this article

Subjects

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 12-month 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 (pā€‰=ā€‰0.008), and hsTn (pā€‰=ā€‰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.

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Fig. 1: Baseline levels of CV biomarkers NTproBNP, D-Dimer, hsTn, and CRP for each patient stratified by study arm and CV event.
Fig. 2: Risk for CV in GnRH agonist vs antagonist, based on baseline levels of cardiac biomarkers grouped by tertiles and current clinical values.
Fig. 3: Levels of biomarkers over time stratified by treatment arm and CV event.

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Acknowledgements

This work was supported as an Investigator Initiated Trial by Ferring Pharmaceuticals (received by DM). The company had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the paper; and decision to submit the paper for publication. Medical writing support was provided by Sam Lommano, Bioscript Science, and support with statistical analyses was provided by Aaron Dane, DaneStat, supported by Ferring Pharmaceuticals.

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Authors and Affiliations

  1. Division of Urology, Rabin Medical Center, Petach Tikva, Israel

    David Margel,Ā Yaara Ber,Ā Liat Shavit-Grievink,Ā Jack BanielĀ &Ā Daniel Kedar

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    David MargelĀ &Ā Jack Baniel

  3. Department of Oncology, Rambam Health Care Campus, Haifa, Israel

    Avivit Peer

  4. Rappaport Faculty of Medicine, Technion, Haifa, Israel

    Avivit Peer

  5. Davidoff Cancer Centre, Rabin Medical Center, Petach Tikva, Israel

    Liat Shavit-GrievinkĀ &Ā Eli Rosenbaum

  6. Department of Surgery, Division of Urology, McMaster University, Hamilton, ON, Canada

    Jehonathan H. Pinthus

  7. Department of Cardiology, Rabin Medical Center, Petach Tikva, Israel

    Guy Witberg

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Contributions

DM, YB, LSG, JHP, JB, and ER conceived and/or designed the study. YB, AP, DK, and ER acquired the data, and DM, YB, and GW had an important role in interpreting the results. All authors were involved in drafting and revising the paper and approved the final version and take responsibility for the work.

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Correspondence to David Margel.

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Conflict of interest

DM and JHP have received honoraria and research grants from Ferring Pharmaceuticals. All other authors have no conflicts of interest to declare.

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Margel, D., Ber, Y., Peer, A. et al. Cardiac biomarkers in patients with prostate cancer and cardiovascular disease receiving gonadotrophin releasing hormone agonist vs antagonist. Prostate Cancer Prostatic Dis 24, 177ā€“185 (2021). https://doi.org/10.1038/s41391-020-0264-9

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