A systematic review and meta-analysis of treatment-induced hypertension risks from androgen receptor pathway inhibitors in randomized controlled trials for prostate cancer.

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.