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May 29, 2026Journal of Clinical Oncology

Association of cardiovascular outcomes with GnRH agonist and antagonist therapy in non-metastatic prostate cancer.

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Why the study?

Randomized trials suggesting GnRH antagonists reduce MACE compared with agonists were limited by short follow-up and low event rates.

Does GnRH antagonist therapy reduce major adverse cardiovascular events compared with GnRH agonists in adult men with non-metastatic prostate cancer?

Population

2,538 matched pairs of adult men with non-metastatic prostate cancer initiating ADT within 1 year of diagnosis

Comparison

GnRH antagonist vs GnRH agonist therapy

Design

Retrospective propensity score-matched cohort study

Follow-up

Years 1-10 following ADT initiation

Key result

GnRH antagonist therapy was associated with a lower risk of MACE compared with GnRH agonists in men with non-metastatic prostate cancer (8.0% vs 9.6%; OR 0.80; 95% CI 0.70-0.99; p=0.05).

Authors

AGAbdulraof GhiblawiGMGhada MohamedTPTirth Patel

Discussion

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Member takes

Overview

May favor GnRH antagonists to lower MACE in prostate cancer; leaves open confirmation in prospective trials.

Key Points

  • Evaluate the relationship between ADT mechanisms and cardiovascular outcomes in non-metastatic prostate cancer.
  • Conducted a retrospective cohort study using TriNetX database
  • Categorized patients by GnRH agonist or antagonist exposure
  • Matched cohorts based on demographics, CV comorbidities, and medications.
  • GnRH antagonist therapy was linked to lower MACE risk (OR 0.80, 95% CI 0.70–0.99; p=0.05) compared to agonists.
  • Among patients with established CVD, antagonist use showed reduced MACE risk (OR 0.77, 95% CI 0.64–0.93; p<0.01).
  • In patients without prior CVD, antagonist use led to significantly lower MACE risk (OR 0.30, 95% CI 0.19–0.52; p<0.01).

Study Design

Type

Cohort (n=5,076)

Multicenter

Yes

Structured PICO

Does GnRH antagonist therapy reduce major adverse cardiovascular events compared with GnRH agonists in adult men with non-metastatic prostate cancer?

P
Population
Adult men with non-metastatic prostate cancer initiating androgen deprivation therapy (ADT) within 1 year of diagnosis (n=5,076).
I
Intervention
GnRH antagonist therapy
C
Comparator
GnRH agonist therapy
O
Outcome
Major adverse cardiovascular events (MACE), defined as myocardial infarction, heart failure exacerbation, stroke or cardiac death, assessed in years 1-10 following ADT initiationcomposite

Main Result

Effect estimate: OR 0.80 (95% CI 0.70-0.99)

Absolute Event Rate: 8% vs 9.6%

p-value: p=0.05

In men with non-metastatic prostate cancer, GnRH antagonist therapy is associated with a significantly lower risk of major adverse cardiovascular events compared to GnRH agonists, regardless of baseline cardiovascular disease status.

Cite This Study

Ghiblawi et al. (2026) conducted a cohort in Non-metastatic prostate cancer (n=5,076). GnRH antagonist vs. GnRH agonist was evaluated on MACE, defined as myocardial infarction, heart failure exacerbation, stroke or cardiac death (OR 0.80, 95% CI 0.70-0.99, p=0.05). GnRH antagonist therapy was associated with a lower risk of MACE compared with GnRH agonists in men with non-metastatic prostate cancer (8.0% vs 9.6%; OR 0.80; 95% CI 0.70-0.99; p=0.05).

synapsesocial.com/papers/6a192ee7fab5b468c44182bdhttps://doi.org/10.1200/jco.2026.44.16_suppl.5123
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