BACKGROUND: Androgen-receptor pathway inhibitors (ARPIs) have dramatically changed the management of advanced/metastatic prostate cancer (PCa). However, their cardiovascular toxicity remains to be clarified. OBJECTIVE: To analyze and compare the risks of cardiovascular events secondary to treatment of PCa patients with different ARPIs. METHODS: In August 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled studies (RCTs) that analyze PCa patients treated with abiraterone, apalutamide, darolutamide, and enzalutamide. The primary outcomes of interest were the incidence of cardiac disorder, heart failure, ischemic heart disease (IHD), atrial fibrillation (AF), and hypertension. Network meta-analyses (NMAs) were conducted to compare the differential outcomes of each ARPI plus androgen deprivation therapy (ADT) compared to standard of care (SOC). RESULTS: Overall, 26 RCTs were included. ARPIs were associated with an increased risk of cardiac disorders (RR: 1.74, 95% CI: 1.13-2.68, p = 0.01), heart failure (RR: 2.49, 95% CI: 1.05-5.91, p = 0.04), AF (RR: 2.15, 95% CI: 1.14-4.07, p = 0.02), and hypertension (RR: 2.06, 95% CI: 1.67-2.54, p < 0.01) at grade ≥3. Based on NMAs, abiraterone increased the risk of grade ≥3 cardiac disorder (RR:2.40, 95% CI: 1.42-4.06) and hypertension (RR:2.19, 95% CI: 1.77-2.70). Enzalutamide was associated with the increase of grade ≥3 AF(RR: 3.17, 95% CI: 1.05-9.58) and hypertension (RR:2.30, 95% CI: 1.82-2.92). CONCLUSIONS: The addition of ARPIs to ADT increases the risk of cardiac disorders, including IHD and AF, as well as hypertension. Each ARPI exhibits a distinct cardiovascular event profile. Selecting patients carefully and vigilant monitoring for cardiovascular issues is imperative for those undergoing ARPI + ADT treatment.

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montréal Health Center Montréal QC Canada

Department of Urology 2nd Faculty of Medicine Charles University Prague Czechia

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology La Croix du Sud Hospital Quint Fonsegrives France

Department of Urology Medical University of Silesia Zabrze Poland

Department of Urology Semmelweis University Budapest Hungary

Department of Urology Shariati Hospital Tehran University of Medical Science Tehran Iran

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology University of Texas Southwestern Medical Center Dallas TX USA

Department of Urology Weill Cornell Medical College New York NY USA

Division of Urology Department of Special Surgery The University of Jordan Amman Jordan

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Research Center for Evidence Medicine Urology Department Tabriz University of Medical Sciences Tabriz Iran

Unit of Urology Urological Research Institute IRCCS San Raffaele Scientific Institute Milan Italy

Vita Salute San Raffaele University Milan Italy

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Prostate Cancer Prostatic Dis. 2024 Oct 7. doi: 10.1038/s41391-024-00902-3. PubMed

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