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. 2025 Apr 15;15(4):1820-1828.
doi: 10.62347/ZUUA2691. eCollection 2025.

Association between immune checkpoint inhibitors and cardiovascular risks: a nationwide self-controlled case series study

Wei-Ting Chang  1   2   3 , Hui-Wen Lin  4 , Chin-Hsiu Liu  3 , Sheng-Hsiang Lin  5   6   7 , Yi-Heng Li  4
Affiliations

Association between immune checkpoint inhibitors and cardiovascular risks: a nationwide self-controlled case series study

Wei-Ting Chang et al. Am J Cancer Res. .

Abstract

Immune checkpoint inhibitors (ICIs) are widely used for cancer treatment but are linked to potential cardiotoxicity. The time-dependent effects of ICIs on cardiovascular outcomes remain unclear. This study explores associations between ICI use and cardiovascular events. This self-controlled case series (SCCS) analyzed cancer patients who received ICIs from January 2019 to December 2020 using the National Health Insurance Research Database (NHIRD). Exposure periods were defined as the duration of ICI prescriptions plus 90 days. Poisson regression estimated incidence rate ratios (IRRs) for heart failure (primary outcome) and arterial events or perimyocarditis (secondary outcomes) during and after ICI exposure compared to baseline. Among 1,146 ICI users, 15 developed heart failure, 33 experienced arterial events, and 11 had perimyocarditis. Cardiovascular events were uncommon but showed elevated risks for heart failure (IRR: 7.73; CI: 2.05-29.14, P<0.01) and perimyocarditis (IRR: 8.25; CI: 1.60-42.50, P = 0.01) within 30 days of ICI exposure. Subgroup analysis identified higher risks in patients aged ≥65, males, and those with diabetes, hypertension, or hyperlipidemia. Furthermore, when focusing on patients who received more than two doses of ICIs or exclusively anti-PD-1 inhibitors, we observed a similarly increased risk of HF within 30 days post-exposure. Collectively, ICI exposure significantly elevates the risk of heart failure and perimyocarditis within 30 days, particularly in older adults and those with preexisting cardiovascular risk factors.

Keywords: Immune checkpoint inhibitors; heart failure; perimyocarditis; self-controlled case series.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
The flowchart of study design.
Figure 2
Figure 2
Subgroup analysis focusing on patients developing heart failure during 0-30 days post immune checkpoint inhibitors.
Figure 3
Figure 3
Using a nationwide self-controlled case series (SCCS) approach, among 1,146 ICI users the exposure of immune checkpoint inhibitors (ICIs) was associated with increasing incodences of cardiovascular complications within 30 days.
See this image and copyright information in PMC

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References

    1. Wojtukiewicz MZ, Rek MM, Karpowicz K, Gorska M, Politynska B, Wojtukiewicz AM, Moniuszko M, Radziwon P, Tucker SC, Honn KV. Inhibitors of immune checkpoints-PD-1, PD-L1, CTLA-4-new opportunities for cancer patients and a new challenge for internists and general practitioners. Cancer Metastasis Rev. 2021;40:949–982. - PMC - PubMed
    1. Marei HE, Hasan A, Pozzoli G, Cenciarelli C. Cancer immunotherapy with immune checkpoint inhibitors (ICIs): potential, mechanisms of resistance, and strategies for reinvigorating T cell responsiveness when resistance is acquired. Cancer Cell Int. 2023;23:64. - PMC - PubMed
    1. Zhang C, Chen Z, Mo C, Gao D, Zhu Y, Qin S, Zuo Z. Real-world cardiovascular toxicity of immune checkpoint inhibitors in cancer patients: a retrospective controlled cohort study. Am J Cancer Res. 2021;11:6074–6085. - PMC - PubMed
    1. Tan S, Sivakumar S, Segelov E, Nicholls SJ, Nelson AJ. Cardiovascular risk factor reporting in immune checkpoint inhibitor trials: a systematic review. Cancer Epidemiol. 2023;83:102334. - PubMed
    1. Zheng Y, Chen Z, Song W, Xu Y, Zhao Z, Sun Y, Wang Y, Geng X, Zhao J, Zhang X, Xu Y, Chan JSK, Tse G, Li G, Hong L, Liu T. Cardiovascular adverse events associated with immune checkpoint inhibitors: a retrospective multicenter cohort study. Cancer Med. 2024;13:e7233. - PMC - PubMed

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