Androgen-receptor pathway inhibitors with ADT increase risk of hypertension (RR~1.6), acute coronary syndrome (RR 2.21), any cardiac events (RR 1.30-1.70), and pulmonary embolism in metastatic prostat
Does the addition of androgen-receptor pathway inhibitors to androgen deprivation therapy increase the risk of cardiovascular adverse events in patients with metastatic prostate cancer?
The addition of androgen-receptor pathway inhibitors to androgen deprivation therapy in metastatic prostate cancer significantly increases the risk of cardiovascular toxicities, including hypertension, ischemic cardiac events, and venous thromboembolism, highlighting the need for proactive cardiovascular risk assessment.
Tasa de eventos absoluta: 0% vs 0%
145 Background: Multiple trials have demonstrated addition of androgen-receptor pathway inhibitors (ARPIs) improve survival in patients with metastatic prostate cancer but there is a need to quantify cardiovascular toxicity. Understanding the nature and extent of ARPI-associated cardiovascular adverse events across disease states and toxicity grades is critical to inform treatment decisions and long-term patient safety. Methods: MEDLINE, and EMBASE were systematically searched from database inception through August 30, 2025, for phase III randomized controlled trials evaluating abiraterone, enzalutamide, apalutamide, darolutamide, orteronel in metastatic prostate cancer. Trials were included if they reported CVS toxicity. Meta-analysis using a random-effects model was performed to assess the difference of all-cause and treatment-emergent cardiovascular adverse events between ARPI+ADT and ADT alone. Summary effects were expressed as relative risk (RR) with associated 95% confidence intervals. Results: A total of 21 trials (45 references) with 25,576 patients (mCSPC: 12,537, mCRPC: 13,039) were included in this meta-analysis. Compared to ADT alone, ARPI+ADT significantly increased the risk of all cause, all grade hypertension in both mCSPC (RR 1.60, 1.22–2.10) and mCRPC (RR 1.61, 1.20–2.16) as well as grade ≥ 3 hypertension (RR 1.71, 1.17–2.48) in mCRPC setting. There was an increased risk of all-cause, all grade acute coronary syndrome (RR 2.21, 1.09–4.49) and AV nodal disease (RR 2.53, 1.18–5.43) with ARPI+ADT compared to ADT alone in mCSPC setting. There was increased risk of all cause, all grade, any cardiac events (RR 1.30, 1.10–1.54) as well as grade ≥ 3 any cardiac events (RR 1.70, 1.20–2.42) in mCRPC setting. Risk of all cause, all grade hot flashes (RR 1.47, 1.16–1.85) was also significantly increased with ARPI+ADT when compared to ADT alone. In terms of treatment-emergent adverse effects, a significant increase was observed only for pulmonary embolism with ARPI+ADT when compared to ADT alone (RR 1.66, 1.06–2.60) in mCRPC setting. Conclusions: Current evidence indicates potentially increased risk of hypertension, venous thromboembolic, and ischemic cardiac events with ARPI therapy in metastatic prostate cancer. Proactive CV risk assessment, particularly in patients with preexisting comorbidities or prolonged ARPI exposure, may optimize outcomes and minimize treatment interruptions. All cause adverse events. Adverse Event Disease State All Grade Grade ≥3 Any Cardiac Event mCSPC 0.81 (0.37–1.76) 0.88 (0.16–4.64) mCRPC 1.30 (1.10–1.54) 1.70 (1.20–2.42) Hypertension mCSPC 1.60 (1.22–2.10) 1.43 (0.82–2.52) mCRPC 1.61 (1.20–2.16) 1.71 (1.17–2.48) ACS mCSPC 2.21 (1.09–4.49) 1.77 (0.86–3.61) mCRPC – – Hot Flashes mCSPC – – mCRPC 1.47 (1.16–1.85) 1.46 (0.21–9.97)
Sadiq et al. (Sun,) reported a other. Androgen-receptor pathway inhibitors with ADT increase risk of hypertension (RR~1.6), acute coronary syndrome (RR 2.21), any cardiac events (RR 1.30-1.70), and pulmonary embolism in metastatic prostat.