Impact of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) on mortality and kidney function in cancer patients receiving cisplatin.

Abstract

11047 Background: Cisplatin is a cornerstone of cancer treatment, but its nephrotoxicity often requires dose reduction or withdrawal, compromising antitumor efficacy. This study aimed to determine if concomitant use of cisplatin with angiotensin-converting enzyme inhibitors (ACEis) or Angiotensin II receptor blockers (ARBs) increases the risk of acute kidney injury (AKI) and impacts mortality. Methods: A retrospective analysis using the TriNetX Research Network identified cancer patients ≥18 treated with cisplatin from January 1, 2010, to November 27, 2024. Eligible cancers included head and neck, lung, esophageal, biliary tract, pancreatic, or testicular cancer. Patients were stratified by ACEi/ARB use within 1 week of cisplatin treatment. Groups were compared using 1:1 propensity matching, adjusting for age, type 2 diabetes, hyperlipidemia, CAD, CHF, and hypertensive heart disease. Primary outcomes were AKI risk and overall mortality; secondary outcomes included renal replacement therapy (RRT), hospitalization within 3 months, and proteinuria or hematuria. Outcomes were assessed using risk analysis and Kaplan-Meier log-rank tests. Results: A total of 36,779 cancer patients taking cisplatin were identified. Of these, 2,585 patients were taking an ACEi/ARB within 1-week of cisplatin treatment, while 36,194 were not. Patients taking ACEis/ARBs had a significantly increased risk of AKI within 30 days of cisplatin use based on the measures of association (risk difference [RD]: 1.713%, p = 0.0152) and the Kaplan-Meier test (hazard ratio [HR]: 1.372, p = 0.01). Similarly, overall mortality was higher in patients with concomitant use of ACEis/ARBs and cisplatin based on both the risk assessment (RD: 5.228%, p = 0.0002) and the Kaplan-Meier (HR: 1.196, p< 0.0001). Patients on ACEis/ARBs also had higher rates of hospitalization 3-months after treatment with cisplatin (RD: 9.24%, p < 0.0001 and HR: 1.53, p < 0.0001). However no significant difference was noted in the need for RRT or the diagnosis of proteinuria or hematuria up to 3-months after treatment. Conclusions: Our study suggests that the use of Cisplatin in patients taking ACEi/ARBs increased the risk of early AKI, mortality, and hospitalizations. Careful consideration should be taken when using Cisplatin in these patient groups, focusing on alternative hypertensive regimens. ACEi/ARB use Risk Difference/Odds Ratio Log-Rank Test Outcomes Yes No RD OR (95% CI) P Value HR 95% CI P-Value AKI Risk 6.82% 5.10% 1.713% (1.06,1.745) 0.0152 1.372 (1.077,1.747) 0.01 Overall Mortality 49.01% 43.78% 5.228% (1.105-1.379) 0.0002 1.196 (1.103-1.297) < 0.0001 Hospitalization 33.44% 24.20% 9.24% (1.393-1.778) < 0.0001 1.534 (1.384-1.702) < 0.0001