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

Author information

Affiliations

  • 1. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
      Authors
    • Matsukawa A 1, 5
    • Yanagisawa T 1, 5
    • Parizi MK 1
    • Laukhtina E 1
    • Klemm J 1
    • Fazekas T 1
    • Mori K 1, 5
    • Kimura S 1, 5
    • Rajwa P 1
    • Shariat SF 1
    (10 authors)
  • 2. Unit of Urology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
      Authors
    • Briganti A 2
    (1 author)
  • 3. Department of Urology, La Croix du Sud Hospital, Quint Fonsegrives, France.
      Authors
    • Ploussard G 3
    (1 author)
  • 4. Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, QC, Canada.
      Authors
    • Karakiewicz PI 4
    (1 author)
  • 5. Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
      Authors
    • Matsukawa A 1, 5
    • Yanagisawa T 1, 5
    • Mori K 1, 5
    • Kimura S 1, 5
    • Miki J 5
    • Kimura T 5
    (6 authors)

ORCIDs linked to this article

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Prostate Cancer and Prostatic Diseases, 05 Sep 2024,
https://doi.org/10.1038/s41391-024-00886-0 PMID: 39237679 

Review

This article has been corrected. See Prostate Cancer Prostatic Dis. 2024 Oct 7. doi: 10.1038/s41391-024-00902-3.

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.

Full text links 

Read article at publisher's site: https://doi.org/10.1038/s41391-024-00886-0

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