Prostate Cancer and Prostatic Diseases https://doi.org/10.1038/s41391-020-00275-3 ARTICLE Clinical Research Abiraterone and enzalutamide had different adverse effects on the cardiovascular system: a systematic review with pairwise and network meta-analyses Hsiang Ying Lee 1,2,3 ● Hsiao-Ling Chen 4 ● Jeremy Yuen-Chun Teoh 5 ● Tun-Chieh Chen 6 ● Shao-Yuan Hao 4 ● Hsin-Yi Tsai 4 ● Wei-Hsuan Huang 4 ● Yung-Shun Juan 1,3 ● Hao-Min Cheng 7,8,9 ● Hsiu-Mei Chang 4 Received: 13 May 2020 / Revised: 13 August 2020 / Accepted: 19 August 2020 © The Author(s), under exclusive licence to Springer Nature Limited 2020 Abstract Background Abiraterone and enzalutamide may increase the risk of cardiovascular events in patients with castration- resistant prostate cancer (CRPC). Methods A comprehensive literature search was performed using a combination of keywords related to “abiraterone,” “enzalutamide,”“prostate cancer,” and “adverse events.” Phase II–IV randomized controlled trials (RCTs) on abiraterone or enzalutamide for patients with nonmetastatic or metastatic CRPC were included. Outcome measures included (1) any grade cardiac disorder, (2) severe grade cardiac disorder, (3) any grade hypertension, and (4) severe grade hypertension, as defined by the Common Terminology Criteria for Adverse Events. Pairwise meta-analysis and Bayesian network meta-analyses were performed to investigate the risk ratios (RRs) of abiraterone and enzalutamide. Surface under cumulative ranking curves (SUCRAs) and cumulative ranking probability plots based on the probability of developing cardiac disorders or hyper- tension were presented. Results A total of 7103 patients from seven RCTs were included. Upon pairwise meta-analysis, abiraterone was associated with increased risks of any grade (RR = 1.34, 95% confidence interval (CI) = 1.05–1.73) and severe grade cardiac disorders (RR = 1.71, 95% CI = 1.16–2.53); enzalutamide was associated with increased risks of any grade (RR = 2.66, 95% CI = 1.93–3.66) and severe grade hypertension (RR = 2.79, 95% CI = 1.86–4.18). Based on the SUCRA rankings, abiraterone had a higher probability of cardiac disorders (84.84% for any grade and 85.12% for severe grade) than enzalutamide (62.83% for any grade and 50.76% for severe grade); whereas enzalutamide had a higher probability of hypertension (99.43% for any grade and 89.71% for severe grade) than abiraterone (49.08% for any grade and 49.37% for severe grade). Conclusions Abiraterone and enzalutamide had different adverse effects on the cardiovascular system. We should take this into consideration when we are deciding on the choice of novel hormonal agents for patients with CRPC. Introduction Prostate cancer is the third commonest malignancy with more than 1.2 million new cases diagnosed in 2018 worldwide [1]. Androgen deprivation therapy (ADT) was first reported in 1940 and it has revolutionized the man- agement of metastatic prostate cancer [2]. ADT is con- sidered the backbone treatment for patients with metastatic prostate cancer. Unfortunately, about one-third of the patients would develop metastatic castration-resistant pros- tate cancer (CRPC) within 2 years [3]. It is also not an uncommon practice to give primary ADT for patients with localized disease [4, 5]. Therefore, a rather distinct disease entity of nonmetastatic CRPC also exists in our clinical practice. Patients who develop CRPC will require additional treatments on top of conventional ADT. There has been a big change in the treatment paradigm of advanced prostate cancer in recent years [6, 7]. In particular, novel hormonal agents have become an important treatment modality across various stages of * Hao-Min Cheng circulation0913@gmail.com * Hsiu-Mei Chang 880504@kmhk.org.tw Extended author information available on the last page of the article Supplementary information The online version of this article (https:// doi.org/10.1038/s41391-020-00275-3) contains supplementary material, which is available to authorized users. 1234567890();,: 1234567890();,: