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Regular use of aspirin is associated with a lower cardiovascular risk in prostate cancer patients receiving gonadotropin-releasing hormone therapy.

ABSTRACT: Gonadotropin-releasing hormone (GnRH) therapy has been known to increase risks of major adverse cardiovascular and cerebrovascular events (MACCEs). Herein, we aim to estimate whether regular use of aspirin attenuates risks of MACCEs in prostate cancer patients receiving GnRHs. Using Taiwanese National Health Insurance Research Database (NHIRD), we identified 7719 patients diagnosed with prostate cancer who were either aspirin-naïve, received irregular or regular aspirin from 2008 to 2015. Through a multivariable logistic regression model, we investigated the impact of aspirin on MACCEs. Compared with nonusers and irregular users, most patients receiving regular aspirin were older and had more comorbidities. The crude incidence of one-year MACCEs was lowest in aspirin nonusers but highest in irregular users of aspirin compared with regular users of aspirin (2.65% vs. 4.41% vs. 2.85%, p=0.0099). After adjusting for age, cancer stage and comorbidities, irregular aspirin users had a higher risk of one-year MACCEs (adjusted OR: 1.33; 95% CI: 0.93-1.90, p=0.1139) than aspirin nonusers, but conversely, there was a trend of reducing the risk of MACCEs among those who received regular aspirin (adjusted OR: 0.79; 95% CI: 0.44-1.42, p=0.4256). In the subgroup analysis, there were age- and cancer stage-independent higher risks of MACCEs in patients who took aspirin irregularly compared to those in patients who did not take aspirin. The risks were attenuated in patients receiving regular aspirin. Collectively, regular use of aspirin presented a trend of reducing risks of MACCEs in prostate cancer patients receiving GnRHs. However, irregular use of aspirin diminished the benefits.

SUBMITTER: Chang WT

PROVIDER: S-EPMC9511956 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Regular use of aspirin is associated with a lower cardiovascular risk in prostate cancer patients receiving gonadotropin-releasing hormone therapy.

Chang Wei-Ting WT Hong Chon-Seng CS Hsieh Kun-Lin KL Chen Yi-Chen YC Ho Chung Han CH Shih Jhih-Yuan JY Kan Wei-Chih WC Chen Zhih-Cherng ZC Lin You-Cheng YC

Frontiers in oncology 20220912

Gonadotropin-releasing hormone (GnRH) therapy has been known to increase risks of major adverse cardiovascular and cerebrovascular events (MACCEs). Herein, we aim to estimate whether regular use of aspirin attenuates risks of MACCEs in prostate cancer patients receiving GnRHs. Using Taiwanese National Health Insurance Research Database (NHIRD), we identified 7719 patients diagnosed with prostate cancer who were either aspirin-naïve, received irregular or regular aspirin from 2008 to 2015. Throug ...[more]

PMID: 36172150

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Project description:Androgen deprivation therapy (ADT) is the main treatment approach in advanced prostate cancer and in recent years has primarily involved the use of gonadotropin-releasing hormone (GnRH) agonists. However, despite their efficacy, GnRH agonists have several drawbacks associated with their mode of action. These include an initial testosterone surge and testosterone microsurges on repeat administration. GnRH antagonists provide an alternative approach to ADT with a more direct mode of action that involves immediate blockade of GnRH receptors. Antagonists produce a more rapid suppression of testosterone (and prostate-specific antigen [PSA]) without a testosterone surge or microsurges and appear to offer an effective and well tolerated option for the hormonal treatment of prostate cancer. Comparisons with GnRH agonists have shown GnRH antagonists to be at least as effective in achieving and maintaining castrate testosterone levels in patients with prostate cancer. Furthermore, with antagonists, the lack of an initial testosterone surge (which may cause clinical flare) may allow more rapid relief of symptoms related to prostate cancer, avoid the need for concomitant antiandrogens to prevent clinical flare (so avoiding any antiandrogen-associated adverse events) and allow GnRH antagonist use in patients with high tumour burden and/or acute problems such as spinal cord compression. Although several antagonists have been investigated, only degarelix and abarelix are currently available for clinical use in prostate cancer. Currently, degarelix is the most extensively studied and widely available agent in this class. Degarelix is one of a newer generation of antagonists which, in a comprehensive and ongoing clinical development programme, has been shown to provide rapid, profound and sustained testosterone suppression without the systemic allergic reactions associated with earlier antagonists. This review examines the currently available data on GnRH antagonists in prostate cancer.

Project description:ImportanceMen with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Meanwhile, gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer (PCa) are associated with increased risk of CVD.ObjectiveTo evaluate the association between GnRH agonist use, PCa diagnosis per se, and CVD risk in men with type 2 diabetes.Design, setting, and participantsThis nationwide population-based cohort study identified men with type 2 diabetes by use of data in the Prostate Cancer Data Base Sweden version 4.1 and the Swedish National Diabetes Register, with longitudinal data from 2006 to 2016. These data were used to create 2 cohorts, 1 including men with and without PCa and the other including men with PCa who received and did not receive GnRH agonists. Data analysis was conducted from January 2006 to December 2016.ExposuresTreatment with GnRH agonists and PCa diagnosis were the primary exposures.Main outcomes and measuresPrimary outcome was a 10% increase in predicted 5-year CVD risk score. Secondary outcome was worsening hypertension as defined by the European Society of Hypertension Guidelines. Cox proportional hazards regression models were used to analyze the association.ResultsThe PCa exposure cohort included 5714 men (median [IQR] age, 72.0 [11.0]), and the non-PCa cohort included 28 445 men without PCa (median [IQR] age, 72.0 [11.0]). The GnRH agonist-exposure cohort included 692 men with PCa who received a GnRH agonist, compared with 3460 men with PCa who did not receive a GnRH agonist. Men with PCa receiving GnRH agonists had an increased estimated 5-year CVD risk score compared with men without PCa (hazard ratio [HR], 1.25; 95% CI, 1.16-1.36) and compared with men with PCa not receiving GnRH agonists (HR, 1.53; 95% CI, 1.35-1.74). Men receiving GnRH agonists had decreased blood pressure compared with men without PCa (HR, 0.70; 95% CI, 0.61-0.80) and compared with men with PCa not receiving GnRH agonists (HR, 0.68; 95% CI, 0.56-0.82).Conclusions and relevanceIn this population-based cohort study, there was an increased risk of CVD in men with type 2 diabetes who received a GnRH agonist for PCa. These findings highlight the need to closely control CVD risk factors in men with type 2 diabetes treated with GnRH agonists. The association between GnRH agonist use and decreased blood pressure levels warrants further study.

Project description:BackgroundGonadotrophin 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.MethodsPost-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.ResultsBaseline 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.ConclusionsThe 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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Regular use of aspirin is associated with a lower cardiovascular risk in prostate cancer patients receiving gonadotropin-releasing hormone therapy.

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Regular use of aspirin is associated with a lower cardiovascular risk in prostate cancer patients receiving gonadotropin-releasing hormone therapy.

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