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. 2025 Jun;28(2):298-308.
doi: 10.1038/s41391-024-00886-0. Epub 2024 Sep 5.

Cardiovascular events among men with prostate cancer treated with androgen receptor signaling inhibitors: a systematic review, meta-analysis, and network meta-analysis

Akihiro Matsukawa  1   2 , Takafumi Yanagisawa  1   2 , Mehdi Kardoust Parizi  1   3 , Ekaterina Laukhtina  1 , Jakob Klemm  1   4 , Tamás Fazekas  1   5 , Keiichiro Mori  1   2 , Shoji Kimura  1   2 , Alberto Briganti  6   7 , Guillaume Ploussard  8 , Pierre I Karakiewicz  9 , Jun Miki  2 , Takahiro Kimura  2 , Pawel Rajwa  1   10 , Shahrokh F Shariat  11   12   13   14   15   16   17   18
Affiliations

Cardiovascular events among men with prostate cancer treated with androgen receptor signaling inhibitors: a systematic review, meta-analysis, and network meta-analysis

Akihiro Matsukawa et al. Prostate Cancer Prostatic Dis. 2025 Jun.

Erratum in

Abstract

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.

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Conflict of interest statement

Competing interests: TK is a paid consultant/advisor of Astellas, Bayer, Janssen and Sanofi. SFS received follows: Honoraria: Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Roche, Takeda Consulting or Advisory Role: Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Pierre Fabre, Roche, Takeda Speakers Bureau: Astellas, Astra Zeneca, Bayer, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Richard Wolf, Roche, Takeda. PR is a paid consultant/advisor of Janssen. The other authors declare no conflicts of interest associated with this manuscript.

Figures

Fig. 1
Fig. 1. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow chart, detailing the article selection process.
PRISMA preferred reporting items for systematic reviews and meta-analyses.
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