Comparative effectiveness of antihypertensive drug classes in patients with gastrointestinal malignancy and incident hypertension.

e16359 Background: Over one-third of patients with cancer require antihypertensive therapy. Emerging evidence suggests renin-angiotensin system (RAS) inhibitors may improve survival in oncology populations, and the 2023 AHA Scientific Statement on Cancer Therapy-Related Hypertension highlights optimal antihypertensive selection as a key evidence gap. We compared outcomes between RAS and non-RAS antihypertensives, and between ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB), in patients with gastrointestinal malignancy and incident hypertension. Methods: Using the TriNetX Research Network (2017-2025), we conducted a retrospective cohort study with a new-user, active-comparator design and propensity score matching. Adults with incident gastrointestinal malignancy (ICD-10 C15-C25) who developed new-onset hypertension requiring antihypertensive initiation within 90 days of cancer diagnosis were included. ACEi/ARB initiators were compared with beta-blocker or calcium channel blocker (BB/CCB) initiators. Cox regression evaluated outcomes starting 91 days post-index. Sensitivity analyses compared ARB with ACEi, BB, and CCB. Results: After matching, 8,440 patient pairs were analyzed. ACEi/ARB initiation was associated with lower all-cause mortality (HR 0.83, 95% CI 0.77-0.90; p < 0.001) and reduced acute kidney injury (HR 0.81, 95% CI 0.70-0.92; p = 0.002). ARB use showed consistent mortality reductions versus ACEi (HR 0.85, 95% CI 0.76-0.96), BB (HR 0.74, 95% CI 0.66-0.84), and CCB (HR 0.76, 95% CI 0.67-0.85). Conclusions: In patients with gastrointestinal malignancy and incident hypertension, RAS inhibitor initiation, particularly ACEi/ARB, was associated with significantly lower mortality and reduced acute kidney injury. These data support preferential first-line use of ACEi/ARB for hypertension management in this population. Summary of primary and sensitivity analyses: Significant outcomes. Comparison N Mortality OR (95% CI) Mortality HR (95% CI) AKI OR (95% CI) AKI HR (95% CI) Thrombosis HR (95% CI) Primary: ACEi/ARB vs BB/CCB 8,440 0.87 (0.80, 0.94)* 0.83 (0.77, 0.90)* 0.86 (0.75, 0.99)* 0.81 (0.70, 0.92)* 0.86 (0.75, 0.98)* Sensitivity 1: ARB vs ACEi 3,622 0.90 (0.79, 1.03) 0.85 (0.76, 0.96)* 1.01 (0.82, 1.25) 0.92 (0.75, 1.13) 0.80 (0.65, 0.99)* Sensitivity 2: ARB vs BB 3,276 0.85 (0.74, 0.97)* 0.74 (0.66, 0.84)* 1.02 (0.81, 1.29) 0.83 (0.67, 1.04) 0.83 (0.66, 1.04) Sensitivity 3: ARB vs CCB 3,901 0.80 (0.70, 0.91)* 0.76 (0.67, 0.85)* 0.89 (0.72, 1.10) 0.81 (0.66, 0.99)* 0.90 (0.72, 1.12) *p < 0.05 (bold text with green shading indicates statistical significance). Abbreviations: OR = odds ratio; HR = hazard ratio; CI = confidence interval; AKI = acute kidney injury; Thrombosis = composite any thrombosis (arterial and venous events combined).