ARNIs May Reduce Mortality and Cardiac Events in Lung Cancer Patients Treated With ICIs: Study
China: Use of angiotensin receptor–neprilysin inhibitors (ARNIs) in lung cancer patients with hypertension receiving immune checkpoint inhibitors (ICIs) was associated with lower all-cause mortality, while rates of cardiac events were similar compared to non-ARNI therapy. As this was a single-center retrospective study, the findings require confirmation through larger, prospective studies.
The study findigns were published online in BMC Cardiovascular Disorders on 27 December 2025.
Immune checkpoint inhibitors have transformed the management of lung cancer, offering meaningful survival benefits for many patients. However, their use is often complicated by immune-related adverse effects, including cardiovascular toxicity. This concern is particularly relevant in patients with pre-existing hypertension, a common comorbidity in the lung cancer population.
Angiotensin receptor–neprilysin inhibitors, widely used in hypertension and heart failure, have demonstrated cardioprotective effects in other settings, but their role in patients receiving ICIs has remained uncertain.
To address this gap, Conghui Shang from the Department of Cardiology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, and colleagues conducted a retrospective analysis to examine whether ARNIs influence outcomes in lung cancer patients with hypertension treated with ICIs. The study included patients who received immunotherapy between September 2019 and May 2024 at a single tertiary care center.
A total of 153 patients met the inclusion criteria. Among them, 39 patients (25.5%) were treated with ARNIs, while 114 patients (74.5%) received other antihypertensive therapies and served as the control group. The primary outcome was all-cause mortality, and the secondary outcome was a composite of cardiovascular events, including myocarditis, heart failure, acute coronary syndrome, pericardial effusion, and new-onset arrhythmias.
The following were the key findings:
- Over a median follow-up of 12 months, 42 patients (27.5%) died.
- ARNI therapy was significantly associated with improved overall survival.
- Patients receiving ARNIs showed markedly higher survival rates than those in the control group.
- The risk of death was substantially lower in the ARNI group, indicating a potential protective effect during immunotherapy.
- Cardiovascular safety outcomes were similar between the ARNI and non-ARNI groups.
- No significant difference was observed in the overall incidence of cardiovascular events between the two groups.
- A total of 24 cardiovascular adverse events occurred during follow-up.
- New-onset arrhythmia was the most common cardiovascular event in both groups, accounting for nearly two-thirds of cases.
- Other cardiovascular events, including heart failure and acute coronary syndromes, were less frequent.
The authors note that these findings suggest ARNIs may confer a survival advantage without increasing cardiovascular risk in this high-risk population. The mechanisms underlying the observed survival benefit remain speculative but may involve improved cardiovascular stability, modulation of neurohormonal pathways, or indirect effects on systemic inflammation, which could influence cancer outcomes during immunotherapy.
Despite its strengths, the study has important limitations. Its retrospective design and single-center setting limit generalizability, and residual confounding cannot be excluded. The relatively small number of patients receiving ARNIs also restricts definitive conclusions.
In summary, the study suggests that ARNI therapy may be associated with lower all-cause mortality without added cardiac risk in lung cancer patients with hypertension treated with ICIs. The authors emphasize that larger, multicenter prospective studies are needed to validate these observations and clarify the role of ARNIs in cardio-oncology practice.
Reference:
Shang, C., Wang, H., Chen, J. et al. Angiotensin receptor-neprilysin inhibitors improve the outcome of lung cancer patients with hypertension undergoing immune checkpoint inhibitors treatment. BMC Cardiovasc Disord (2025). https://doi.org/10.1186/s12872-025-05466-1
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