Cardiovascular Adverse Events Associated With New-Generation Androgen Receptor Pathway Inhibitors (ARPI) for Prostate Cancer: A Disproportionality Analysis Based on the FDA Adverse Event Reporting System (FAERS)

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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Assessment of Cardiovascular Events Caused by New-Generation Androgen Receptor Pathway Inhibitors Used for Prostate Cancer: A Real-World Study in Japan

Masuda,

Noguchi,

Aizawa

et al. 2024

Oncology

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Introduction: Androgen receptor pathway inhibitors (ARPI) that significantly improve the prognosis of patients with prostate cancer include abiraterone acetate (androgen synthesis inhibitor) and enzalutamide (androgen receptor inhibitor). A recent analysis of ARPI and cardiovascular events using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) has been reported; however, the evidence on cardiovascular events for abiraterone acetate and enzalutamide in real-world clinical practice is insufficient. Using a large Japanese database of medical institutions, the Japanese Medical Data Center (JMDC) medical institution database (JMDC Inc., Tokyo, Japan), this study tested the hypothesis that the risk of cardiovascular events with enzalutamide is lower than that with abiraterone acetate. Method: Using the JMDC medical institution database, patients with new use of abiraterone acetate or enzalutamide who had not experienced a major cardiovascular event between October 2014 and February 2022 were included. After adjusting for age, comorbidities, and concomitant medications using propensity score matching, cumulative incidence rates were compared for cardiovascular death and all cardiovascular events as the primary endpoints, and major cardiovascular events, myocardial infarction, heart failure, and stroke as secondary endpoints. Result: A total of 3,033 patients in the enzalutamide group and 2,021 in the abiraterone group met the eligibility criteria. After propensity score matching, the cohort included 1,940 patients in the enzalutamide group and 1,940 in the abiraterone group. Enzalutamide was associated with significantly lower cumulative rates of cardiovascular death (hazard ratio [HR]: 0.30, 95% Confidence interval [CI]: 0.10–0.93), all cardiovascular events (HR: 0.79, 95% CI: 0.64–0.98), major cardiovascular events (HR: 0.79, 95% CI: 0.64–0.97), and myocardial infarction (HR: 0.62, 95% CI: 0.46–0.84) compared to abiraterone. Conclusion: In a national sample of males with prostate cancer, those newly treated with enzalutamide had a lower risk of adverse cardiovascular events than those treated with abiraterone acetate.

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Cardiovascular Adverse Events Associated With New-Generation Androgen Receptor Pathway Inhibitors (ARPI) for Prostate Cancer: A Disproportionality Analysis Based on the FDA Adverse Event Reporting System (FAERS)

Cited by 4 publications

References 43 publications

Androgen receptor pathway inhibitor-related MACE

Androgen receptor pathway inhibitor-related MACE

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

Assessment of Cardiovascular Events Caused by New-Generation Androgen Receptor Pathway Inhibitors Used for Prostate Cancer: A Real-World Study in Japan

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