Comparison of cardiovascular events in patients with metastatic hormone sensitive prostate cancer treated with LHRH agonists to LHRH antagonists in the US: A retrospective cohort study.
LHRH agonists appear to be associated with a lower risk of major cardiovascular events compared to LHRH antagonists in patients with metastatic hormone-sensitive prostate cancer, but further research is needed to validate these results.
Where it sits
this study against the rest of the triptorelin corpusSummary and findings
This study compared the incidence of major adverse cardiovascular events (MACE) in patients with metastatic hormone-sensitive prostate cancer treated with LHRH agonists versus LHRH antagonists. The primary outcome was MACE, including myocardial infarction, stroke, and all-cause mortality, assessed in a cohort of 6,658 patients after propensity-score matching. LHRH agonists were associated with a decreased risk of MACE compared to LHRH antagonists.
Abstract
Androgen deprivation therapy (ADT) is standard treatment for metastatic hormone-sensitive prostate cancer (mHSCaP). Patients receive LHRH-agonists (LHRH-AG: leuprolide, goserelin or triptorelin) or LHRH-antagonists (LHRH-AN: degarelix or relugolix) with intensification with androgen receptor pathway inhibitors, with or without chemotherapy. Given ongoing concerns about cardiovascular risk, we used real-world data from TriNetX to compare the incidence of major adverse cardiovascular events (MACE) between patients receiving LHRH-AG vs. LHRH-AN. We included adult patients with mHSCaP who received either an LHRH-AG or LHRH-AN. The composite primary outcome was MACE (defined as myocardial infarction (MI), stroke, or all-cause mortality). Secondary outcomes were MI, stroke, and all-cause mortality. Patients were 1:1 propensity-score matched (PSM). Kaplan-Meier analysis reporting hazard ratios (HR) and 95% confidence intervals (CI) for the outcomes was conducted. We conducted a subgroup analysis to assess the effect of intensification of therapy. Exploratory analyses were conducted to assess HR of outcomes and new-onset metabolic comorbidities (diabetes mellitus, insulin use, hypertension, and dyslipidemia) amongst patients without cardiovascular risk factors. Before PSM, there were 27,051 in LHRH-AG and 3,339 in LHRH-AN cohorts. After PSM, 3,329 patients in each cohort were compared. Compared to LHRH-AN, LHRH-AG was associated with a decreased risk of MACE (hazard ratio [HR] = 0.86, 95% CI: 0.79-0.93), MI (HR = 0.80, 95% CI: 0.66-0.97), and any-cause mortality (HR = 0.85, 95% CI: 0.78-0.93). Treatment intensification did not modify the association between MACE outcomes and LHRH-AG vs. LHRH-AN. Using real-world data, LHRH-AG was associated with a decreased risk of experiencing MACE. Among those undergoing intensification of therapy, there was no difference in MACE risk associated with LHRH-AG vs. LHRH-AN.
Background
This paper addresses the cardiovascular risks associated with androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSCaP). Prior studies have raised concerns about the cardiovascular safety of LHRH agonists compared to antagonists. Understanding these risks is crucial for optimizing treatment strategies in this patient population.
Methods
The study utilized a retrospective cohort design using data from TriNetX. Adult patients with mHSCaP treated with either LHRH agonists or antagonists were included. The primary outcome was the composite of major adverse cardiovascular events (MACE), while secondary outcomes included myocardial infarction, stroke, and all-cause mortality. Propensity-score matching was performed to create balanced cohorts for comparison.
Results
The primary finding indicated that LHRH agonists were associated with a decreased risk of MACE, with a hazard ratio of 0.86 (95% CI: 0.79-0.93). Additionally, the risk of myocardial infarction was lower in the LHRH agonist group, with an HR of 0.80 (95% CI: 0.66-0.97). The risk of all-cause mortality was also reduced, with an HR of 0.85 (95% CI: 0.78-0.93).
Interpretation
These findings suggest that LHRH agonists may pose a lower cardiovascular risk compared to antagonists, which aligns with some previous literature. However, the effect sizes, while statistically significant, may not be clinically meaningful in all contexts. The retrospective nature of the study and reliance on real-world data introduce potential confounding factors that could affect the validity of the conclusions.
Key findings
- HR for MACE with LHRH-AG vs LHRH-AN was 0.86 (95% CI: 0.79-0.93)
- HR for myocardial infarction with LHRH-AG vs LHRH-AN was 0.80 (95% CI: 0.66-0.97)
- HR for all-cause mortality with LHRH-AG vs LHRH-AN was 0.85 (95% CI: 0.78-0.93)
- Before propensity-score matching, there were 27,051 patients in the LHRH-AG cohort and 3,339 in the LHRH-AN cohort
- After propensity-score matching, 3,329 patients in each cohort were compared
Limitations
- retrospective cohort study
- relies on real-world data
- potential confounding factors not controlled
- no long-term outcome data reported