Abstract
Controversy exists regarding the risk of cardiovascular disease (CVD) associated with androgen deprivation therapy (ADT) in patients with prostate cancer. We sought to evaluate the association between gonadotropin-releasing hormone (GnRH) agonists versus GnRH antagonist and the risk of CVD in patients with prostate cancer with or without prior CVD. Using administrative databases from Quebec, Canada, we identified first-time GnRH agonists and antagonist (degarelix) users between January 2012 and June 2016. Follow-up ended at the earliest of the following: first CVD event (myocardial infarction [MI], stroke, ischemic heart disease [IHD], arrhythmia, and heart failure [HF]); switch of GnRH group; death; or December 31, 2016. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to control for potential confounding. IPTW-Cox proportional hazards model accounting for competing risks was used to evaluate the association of interest. Among 10,785 patients identified, 10,201 and 584 were on GnRH agonists and antagonist, respectively. Median age was 75 years (interquartile range, 69-81 years) for both groups. A total of 4,152 (40.7%) men in the GnRH agonists group and 281 (48.1%) men in the GnRH antagonist group had CVD in the 3-year period prior to ADT initiation. Risk of HF was decreased in the antagonist group compared with the GnRH agonist group among patients with prior CVD (hazard ratio [HR], 0.46; 95% CI, 0.26-0.79). Risk of IHD was decreased in the antagonist group in patients without prior CVD (HR, 0.26; 95% CI, 0.11-0.65). Use of antagonist was associated with an increased risk of arrhythmia among patients with no prior CVD (HR, 2.34; 95% CI, 1.63-3.36). Compared with GnRH agonists, the GnRH antagonist was found to be associated with a decreased risk of HF, specifically among patients with prior CVD. Among those with no prior CVD, the GnRH antagonist was associated with a decreased risk of IHD but an increased risk of arrhythmia.
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