OBJECTIVE: Androgen receptor pathway inhibitors (ARPIs) have revolutionized prostate cancer treatment, but their cardiovascular safety profile requires comprehensive evaluation. This meta-analysis aims to examine the association between ARPI use and hypertension risk in prostate cancer patients. METHODS: We systematically searched PubMed, Web of Science, and ClinicalTrials.gov for randomized controlled trials comparing ARPIs with control. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models for all-grade and grade ≥ 3 hypertension. Subgroup analyses were performed by individual ARPI agents and combination therapies. RESULTS: Twenty-two studies (derived from 21 distinct randomized controlled trials) involving 22,420 patients were included for analysis. ARPIs significantly increased the risk of all-grade hypertension (RR 1.82, 95% CI 1.51-2.21, p < 0.001). Combination therapy with abiraterone plus enzalutamide showed the highest risk (RR 3.46, 95% CI 2.96-4.05), followed by enzalutamide monotherapy (RR 2.20, 95% CI 1.67-2.91) and abiraterone monotherapy (RR 1.46, 95% CI 1.20-1.78). For grade ≥ 3 hypertension, ARPIs significantly increased risk (RR 2.17, 95% CI 1.68-2.81, p < 0.001) with similar subgroup patterns. Darolutamide and apalutamide demonstrated relatively favorable cardiovascular safety profile among monotherapies. CONCLUSION: ARPI treatment significantly increases hypertension risk in prostate cancer patients, with substantial variability among specific agents and regimens. Combination therapy poses the highest risk, while darolutamide demonstrated a lower risk profile in this indirect comparison. These findings support routine blood pressure monitoring and aggressive management in patients receiving ARPI therapy, particularly those with pre-existing cardiovascular risk factors.
Gong et al. (Wed,) studied this question.