Association between concomitant ACEI/ARBs use and survival of patients with prostate cancer receiving abiraterone acetate: A post-hoc analysis of two randomized trials

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of non-cancer mortality in prostate cancer (PCa) patients. The management of CVD, including hypertension, holds equal significance to cancer treatment. However, the optimal antihypertensive agent for blood pressure management in PCa patients receiving abiraterone acetate (AA) is still unclear. This study aims to investigate the association between various antihypertensive regimens and survival outcomes in PCa patients treated with AA. METHODS: We performed a post-hoc observational analysis using data from COU-AA-301 and COU-AA-302. Radiographic progression-free survival (rPFS), overall survival (OS) and prostate cancer-specific survival (PCSS) were evaluated using the Kaplan-Meier method. Cox proportional hazards models were used to obtain hazard ratios (HRs) and associated 95% confidence intervals (CIs). RESULTS: Among the AA groups of COU-AA-301 and COU-AA-302, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) monotherapy was associated with longer rPFS (HR 0.82, 95% CI 0.59-1.13; HR 0.71, 95% CI 0.53-0.95), OS (HR 0.66, 95% CI 0.41-1.06; HR 0.70, 95% CI 0.53-0.92) and PCSS (HR 0.72, 95% CI 0.44-1.19; HR 0.67, 95% CI 0.49-0.92). Multiple-class antihypertensive treatment regimens including ACEI/ARBs were associated with longer rPFS (HR 0.74, 95% CI 0.59-0.92; HR 0.71, 95% CI 0.54-0.94), OS (HR 0.76, 95% CI 0.57-1.01; HR 0.72, 95% CI 0.55-0.94) and PCSS (HR 0.71, 95% CI 0.51-0.99; HR 0.62, 95% CI 0.46-0.83). Multivariable analysis indicated that ACEI/ARBs were associated with improved rPFS (HR 0.72, 95% CI 0.60-0.86; HR 0.75, 95% CI 0.60-0.94), OS (HR 0.71, 95% CI 0.56-0.91; HR 0.70, 95% CI 0.56-0.88) and PCSS (HR 0.73, 95% CI 0.55-0.96; HR 0.64, 95% CI 0.50-0.82). CONCLUSIONS: In this post-hoc analysis, concomitant use of ACEI/ARBs was associated with longer rPFS, OS and PCSS in PCa patients treated with AA. The potential role of ACEI/ARB-containing antihypertensive regimens in these patients warrants further investigation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00638690, NCT00887198.