Abstract Body: Background:
Although ARNI (sacubitril-valsartan) offers a mortality benefit over ACE inhibitors or ARBs in heart failure (HF), cost remains a barrier. Among ACE and ARBs, clinician preference and adverse effects—such as angioedema and cough—often influence treatment decisions.
Hypothesis:
We compared outcomes between ACE inhibitors and ARBs in patients with both HF and hypertension (HTN).
Methods:
This retrospective real-world cohort study used the TriNetX Global Collaborative Network. Adult patients aged ≥40 years, diagnosed with both HF and HTN from Jan 2007 to May 2025, were included. Patients were divided into two treatment cohorts: ACE inhibitors (n = 500,282) and ARBs (n = 500,282). Propensity score matching (1:1) balanced demographics, comorbidities, and medications. Outcomes included all-cause mortality, incident HF, stroke (CVA), atrial fibrillation (AF), and kidney impairment (AKI or CKD). Risk ratios (RR), hazard ratios (HR), 95% confidence intervals (CI), and p-values were calculated using the TriNetX platform.

Results:
After matching, ACE inhibitor users had higher all-cause mortality (31.74%) than ARB users (23.98%), RR 1.324 (95% CI: 1.316–1.332), HR 1.129 (95% CI: 1.121–1.138), p < 0.0001. Incident HF was similar between groups (82.02% ACE vs. 81.81% ARB), RR 1.003 (95% CI: 1.001–1.004), HR 0.972 (95% CI: 0.968–0.976), p = 0.0066. Stroke occurred more often in the ACE group (13.13%) vs. ARB (11.42%), RR 1.15 (95% CI: 1.138–1.162), HR 1.045 (95% CI: 1.034–1.057), p < 0.0001. AF was seen in 45.87% of ACE users vs. 44.46% of ARB users (RR 1.032, HR 0.981, both p < 0.0001). Kidney impairment affected 55.16% of ACE patients vs. 51.42% in the ARB group, RR 1.073 (95% CI: 1.069–1.077), HR 1.018 (95% CI: 1.012–1.023), p < 0.0001.
Conclusion:
ARBs were associated with lower all-cause mortality and reduced cardiovascular, CVA, and renal events compared to ACE inhibitors. Further research is needed to assess long-term comparative outcomes in HF and HTN patients.