Abstract Body (Do not enter title and authors here): Background: Degarelix is a third-generation GnRH receptor antagonist approved for the treatment of prostate cancer. Recent data shows that the use of GnRH agonists is associated with higher cardiovascular morbidity and mortality and, suggesting the shorter time to testosterone suppression and lack of testosterone surge, GnRH antagonists might be more clinically beneficial.
Purpose: We aimed to perform a meta-analysis comparing the cardiovascular disease risk between degarelix and gonadotropin-releasing hormone agonists in patients with all stages of prostate cancer.
Methods: PubMed, Scopus and Web of Science databases were searched for randomized control trials (RCTs) and observational studies assessing the cardiovascular disease risk between degarelix and GnRH agonists in patients with prostate cancer. The outcomes of interest were (1) Cardiovascular Disease Risk, (2) Major Adverse Cardiovascular Events, (3) Stroke, (4) All-Cause Death, (5) Myocardial Infarction, (6) Heart Failure, (7) Arrhythmia, and (8) Hypertension. We computed binary endpoints risk ratio (RR) or hazard ratio (HR) with 95% confidence intervals (CI), which were analyzed using a random-effects model. Heterogeneity was examined with I2 statistics. P values of ≤ 0.05 were considered statistically significant. Statistical analyses were performed using RStudio, version 4.2.3.
Results: 8 RCTs and 7 observational studies were included (123,969 patients; mean age 75 years; 12 months follow-up). Degarelix was associated with a significantly lower incidence of major adverse cardiovascular events (10.30% degarelix vs. 31.01% GnRH agonists; RR 0.59; 95% CI 0.41, 0.84; p = 0.003; I2=84%). Incidence of stroke (1.04% degarelix vs. 2.56% GnRH agonists; RR 0.89; 95% CI 0.56, 1.42; p = 0.62; I2=0%), all-cause mortality (3.15% degarelix vs. 5.24% GnRH agonists; RR 0.64; 95% CI 0.37, 1.13; p = 0.12; I2=41%), hypertension (4.05% degarelix vs. 5.78% GnRH agonists; RR 0.71; 95% CI 0.48, 1.04; p = 0.08; I2=0%), myocardial infarction (HR 1.04; 95% CI 0.59, 1.84; p=0.86; I2=66%), heart failure (HR 0.79; 95% CI 0.38, 1.62; p=0.52; I2=79%) and arrhythmia (4.58% degarelix vs. 10.67% GnRH agonists; RR 0.63; 95% CI 0.28, 1.41; p = 0.86; I2=37%), did not reach a statistically significant difference between groups.
Conclusion: In patients with prostate cancer, degarelix is associated with a significantly lower incidence of major adverse cardiovascular events.