Abstract
Background and purpose:
With the widespread application of immune checkpoint inhibitors (ICIs) in cancer treatment, the associated risk of developing atherosclerotic cardiovascular injury is increasing. However, the risk of cardiovascular disease after ICI treatment in patients with both coronary artery disease and malignancy remains unclear. This study aimed to investigate whether ICI treatment is associated with an increased risk of major adverse cardiovascular events (MACE) in these high-risk patients.
Methods:
This single-center, retrospective cohort study included 93 patients diagnosed with coronary heart disease and malignant tumors who received ICIs or non-ICIs therapy. The primary outcome was MACE, defined as a composite of cardiogenic death, heart failure, non-fatal acute coronary syndrome, and non-fatal ischemic stroke. The association between baseline clinical parameters, including ICI exposure, and the incidence of MACE was evaluated.
Results:
During a median follow-up of 14 months, MACE occurred in 32.50% of ICIs-treated patients, with a median time to event of 4 months (2.0–8.5 months), compared to 11.32% and 15.5 months (7.8–27.0 months) in non-ICIs patients. Additionally, all-cause mortality occurred in 12.50% of the ICIs-treated group and 13.21% of the non-ICIs group. Traditional cardiovascular risk factors were not associated with MACE in patients with or without ICI treatment. Multivariable regression analyses revealed an increased risk of developing MACE following ICIs therapy (hazard ration [HR]: 2.86, 95% confidence interval [95% CI]: 1.01–8.11; P = 0.048).
Conclusions:
Our findings show that ICIs therapy may be independently associated with an increased risk of MACE in patients with coronary heart disease and malignancy. Further larger-scale studies are needed to validate the potential cardiotoxic risk associated with ICIs.
Keywords: Coronary artery disease, Immune checkpoint inhibitor, Major adverse cardiac events, Neoplasms
INTRODUCTION
As a rapidly developing cancer treatment, immune checkpoint inhibitors (ICIs) have substantially improved clinical outcomes for many types of cancer by targeting checkpoint activity and inhibiting T cells, thereby activating an anti-tumor immune response[1]. However, immune tolerance mediated by ICIs has been associated with immune-related cardiac adverse events (irCAEs), predominantly myocarditis; pericarditis disease, Takotsubo-like cardiomyopathy, and arrhythmias have also been reported, typically occurring within six weeks after ICI initiation.
In addition, ICIs have been found to regulate key pathways involved in arterial chronic inflammation, leading to the formation and progression of atherosclerotic plaques. Large observational studies have demonstrated an increased risk of atherosclerotic plaque progression and atherosclerotic cardiovascular disease (ASCVD) in patients treated with ICIs[2–3]. Nevertheless, there is limited clinical evidence assessing the residual risk of ASCVD in patients with both coronary artery disease (CAD) and malignant tumors following ICIs therapy.
Given the considerable cardiovascular risk burden in cancer patients, who share common risk factors, and the fact that the ASCVD risk associated with ICIs appears to be independent of traditional atherosclerotic disease risk factors[2,4], we hypothesize that ICIs therapy significantly increases the risk of atherosclerotic progression in patients with CAD and malignancy. Therefore, this study aimed to investigate the risk of major adverse cardiovascular events (MACE) in patients with coronary heart disease and malignant tumors following ICIs treatment.
METHODS
Study population
Patients diagnosed with CAD and malignant tumors at Fudan Zhongshan Hospital, Shanghai, China, between August 2020 and July 2023 were included in this retrospective cohort study. CAD is a dynamic process of atherosclerotic plaque accumulation that can present as either acute coronary syndromes or chronic coronary syndrome. In this study, patients with CAD were defined as those with ≥50% coronary artery stenosis who have received medical therapy alone, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG).
Inclusion criteria
The inclusion criteria were as follows: (1) age ≥ 18 years; (2) diagnosis of CAD according to the European Society of Cardiology (ESC) guidelines[5]; (3) diagnosis of malignant tumors according to corresponding National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology; and (4) diagnosis of coronary atherosclerotic disease before initiation of ICIs therapy start.
Exclusion criteria
Exclusion criteria were as follows: (1) severe heart, liver, kidney, lung, and other important organ insufficiency; (2) coagulation dysfunction; and (3) high risk of bleeding that precluded standardized treatment for coronary heart disease.
The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by the Ethics Committee of Zhongshan Hospital Affiliated to Fudan University (Grant No. B2021-275, May 2021). Due to the retrospective nature of the study, the requirement for informed consent was waived by the ethics committee.
Procedures
A total of 120 patients were initially enrolled, of whom 27 were excluded due to loss to follow-up. Among patients hospitalized for cancer, those with a history of CAD were included. Patients who received ICIs after being diagnosed with both CAD and malignant tumors were classified as the ICIs group (n = 40), while those who did not receive ICIs were classified as the non-ICIs group (n = 53).
Baseline information was collected at the beginning of the first course of anti-tumor therapy (non-ICIs group) or ICIs treatment (ICIs group). Patient characteristics at baseline were collected from medical records which include: (1) general information: age, gender, smoking and alcohol history; (2) standard cardiovascular risk factors: hypertension, diabetes, cerebrovascular disease, chronic kidney disease, atrial fibrillation, heart failure, peripheral vascular disease, and related medications; (3) coronary artery conditions: medical therapy alone, PCI, or CABG; (4) serum lipids: triglycerides (TGs), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and non-high-density lipoprotein cholesterol (nHDL-C); (5) cancer characteristics: pathological types, tumor stages, prior or concurrent cancer therapies (radiation therapy, 5-fluorouracil, anthracyclines, human epidermal growth factor receptor 2 inhibitors, vascular endothelial growth factor inhibitors [VEGFs], and tyrosine kinase inhibitors) and ICIs types.
Diseases were identified according to the International Classification of Disease, 10th Revision, Clinical Modification (ICD-10-CM). The study endpoint was the occurrence of MACE, defined as a composite of cardiogenic death (ICD-10-CM code: I23, I46, I49, I51), heart failure (ICD-10-CM code: I50), non-fatal acute coronary syndrome (ICD-10-CM code: I20, I21), and non-fatal ischemic stroke (ICD-10-CM code: I63-I66)[6]. Tumor response was evaluated according to Response Evaluation Criteria in Solid Tumors 1.1[7]. All patients were followed until August 2024 or death.
Statistical analysis
Statistical analyses were performed using SPSS version 25.0 (IBM Corp., Armonk, NY, USA). Continuous variables were summarized as mean ± standard deviation or medians with interquartile range (IQR, 25th–75th percentile), while categorical variables were presented as counts with percentages. Continuous variables were compared using t test or Mann-Whitney test, and categorical variables were compared using the Pearson χ2 test.
Cumulative incidence curves were constructed using the Kaplan-Meier method, and differences between groups were evaluated by the log-rank test. To determine risk factors for ASCVD events, univariable and multivariable regression analyses were performed using the Cox proportional hazard (PH) model to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Candidate variables with a P value <0.1 in the univariable analysis were included in the multivariable model. Covariates included age, sex, smoking, hypertension, diabetes mellitus, hyperlipidemia, coronary artery conditions, pre-treatment cardiovascular medications, and prior or concurrent anti-cancer therapy. PH assumption was verified using log-log survival plots. A P value<0. 05 was considered statistically significant.
RESULTS
Patient characteristics
A total of 93 patients were included in this study, comprising 40 (43%) patients who received ICIs therapy and 53 (57%) patients who did not. Baseline demographics and clinical characteristics are shown in Table 1.
Table 1.
Baseline characteristics of patients by treatment
| Variables | Non-ICIs group (n = 53) | ICIs group (n = 40) | P value |
|---|---|---|---|
| Age at start of treatment, years | 68.49 ± 6.71 | 67.63 ± 7.03 | 0.483 |
| Female | 4 (7.55) | 5 (12.50) | 0.424 |
| Smoking history | 20 (37.74) | 18 (45.00) | 0.480 |
| Drinking history | 11 (20.75) | 10 (25.00) | 0.628 |
| Pre-treatment comorbidities | |||
| Hypertension | 28 (52.83) | 22 (55.00) | 0.835 |
| Diabetes mellitus | 23 (43.40) | 15 (37.50) | 0.567 |
| Cerebrovascular disease | 4 (7.55) | 1 (2.50) | 0.285 |
| Chronic kidney disease* | 2 (3.77) | 1 (2.50) | 0.731 |
| Atrial fibrillation | 5 (9.43) | 2 (5.00) | 0.422 |
| Heart failure | 6 (11.32) | 1 (2.50) | 0.110 |
| Peripheral arterial disease | 5 (9.43) | 2 (5.00) | 0.422 |
| Coronary artery conditions | |||
| Received medical therapy alone | 19 (35.85) | 12 (30.00) | 0.554 |
| Received PCI | 34 (64.15) | 27 (67.5) | 0.736 |
| Received CABG | 0 (0) | 1 (2.50) | 0.247 |
| Pre-treatment cardiovascular medications | |||
| Aspirin | 38 (71.70) | 21 (52.50) | 0.057 |
| Other antiplatelet therapies | 39 (73.58) | 31 (77.50) | 0.665 |
| Anticoagulant medications | 5 (9.43) | 4 (10.00) | 0.927 |
| Statin | 47 (88.68) | 29 (72.50) | 0.046 |
| PCSK9 inhibitor | 3 (5.66) | 3 (7.50) | 0.721 |
| Beta-blockers | 22 (41.51) | 17 (42.50) | 0.924 |
| ACE inhibitor or ARB | 15 (28.30) | 10 (25.00) | 0.722 |
| Aldosterone receptor antagonist | 2 (3.77) | 0 (0) | 0.214 |
| SGLT2 inhibitor | 2 (3.77) | 1 (2.50) | 0.731 |
| Nitrates | 1 (1.89) | 0 (0) | 0.382 |
| Serum lipid | |||
| TG, mmol/L | 1.63 [0.95, 1.94] | 1.35 [1.10, 2.13] | 0.932 |
| TC, mmol/L | 3.68 ± 0.98 | 3.68 ± 1.03 | 0.984 |
| LDL-C, mmol/L | 2.00 ± 0.91 | 2.07 ± 0.86 | 0.748 |
| HDL-C, mmol/L | 0.98 ± 0.22 | 1.02 ± 0.23 | 0.363 |
| nHDL-C, mmol/L | 2.81 ± 1.01 | 2.60 ± 0.99 | 0.302 |
| HbA1c, % | 5.98 ± 0.66 | 6.48 ± 0.96 | 0.005 |
| Cancer type | |||
| Gastrointestinal cancer | 34 (64.15) | 19 (47.50) | 0.108 |
| Hepatocarcinoma | 4 (7.55) | 3 (7.50) | 0.993 |
| Lung cancer | 11 (20.75) | 9 (22.50) | 0.839 |
| Renal cell carcinoma | 1 (1.85) | 3 (7.50) | 0.205 |
| Other | 3 (5.66) | 6 (15.00) | 0.131 |
| Cancer stage | |||
| I-III stage | 22 (41.51) | 16 (40.00) | 0.883 |
| IV stage | 31 (58.49) | 24 (60.00) | 0.883 |
| Prior or concurrent anti-cancer therapy | |||
| Radiation | 12 (22.64) | 13 (32.50) | 0.288 |
| 5-fluorouracil | 16 (30.19) | 13 (32.50) | 0.812 |
| Anthracyclines | 3 (5.66) | 3 (7.50) | 0.721 |
| HER2 inhibitors | 2 (3.77) | 0 (0) | 0.203 |
| VEGF inhibitors | 2 (3.77) | 7 (17.50) | <0.001 |
| TKI | 12 (22.64) | 8 (20.00) | 0.759 |
| ICIs types | |||
| PD-1 antibody | 0 (0) | 36 (90.00) | - |
| PDL-1 antibody | 0 (0) | 3 (7.50) | - |
| CTLA-4 antibody | 0 (0) | 0 (0) | - |
| CTLA-4 and PD-1 antibody | 0 (0) | 1 (2.50) | - |
Values are presented as mean ± standard deviation or n (%), or median with inquartile.
Chronic kidney disease = glomerular filtration rate < 60 mL/min/1.73 m2.
ACE: angiotensin-converting enzyme; ARB: angiotensin II receptor blockers; CABG: coronary artery bypass grafting; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein cholesterol; HER2: human epidermal growth factor receptor 2; ICIs: immune checkpoint inhibitors; LDL-C: low-density lipoprotein cholesterol; nHDL-C: non-high-density lipoprotein cholesterol; PCI: percutaneous coronary intervention; PCSK9: proprotein convertase subtilisin/kexin type 9; PD-1: programmed cell death protein-1; PDL-1: programmed death-ligand-1; SGLT2: sodium-glucose co-transporter 2; TC: total cholesterol; TG: triglycerides; TKI: tyrosine kinase inhibitors; VEGF: vascular endothelial growth factor.
Overall, the ICIs group had a higher proportion of patients treated with VEGF inhibitors (17.50% vs. 3.77%, P < 0.001) and higher hemoglobin A1c (HbA1c) levels (6.48% ± 0.96% vs. 5.98% ± 0.66%, P = 0.005). The proportion of patients receiving statins treatment was higher in the non-ICIs group than in the ICIs group (88.68% vs.72.50%, P = 0.046). No significant differences were observed between the two groups in other baseline characteristics, including age, gender, cardiovascular risk factors, coronary artery conditions, cancer type or stage, and other anti-cancer treatments. Interestingly, the proportion of female patients in both groups was unusually low, which may be attributed to the study’s inclusion criteria requiring a diagnosis of CAD, as the incidence of major cardiovascular disease was lower in women than in men[8].
Gastrointestinal and lung cancer were the most common malignancies in both groups (64.15% and 20.75% vs. 47.50% and 22.50%, respectively; P > 0.05). In the ICIs group, programmed cell death protein-1 (PD-1) antibodies were the most frequently administered type of immune checkpoint inhibitor (90.00%).
Major adverse cardiovascular events
During a median follow-up of 14 months (IQR: 12–36 months), all-cause mortality was 12.50% in the ICIs group and 13.21% in the non-ICIs group (P = 0.920, Table 2). A total of 13 MACE (32.50%) occurred in the ICI group during follow-up, with a median time to event of 4 months (2.0–8.5 months), including 11 myocardial infarctions (27.50%) and 2 cases of heart failure (5.00%). In the non-ICIs group, 6 MACE (11.32%) occurred, with a median time to event of 15.5 months (IQR: 7.8–27.0 months), comprising one cardiogenic death (1.89%), four myocardial infarctions (7.55%), and one heart failure (1.89%, Table 2).
Table 2.
All-cause mortality and incidence of MACE
| Variables | Non-ICIs group (n = 53) | ICIs group (n = 40) | P value |
|---|---|---|---|
| All-cause mortality | 7 (13.21) | 5 (12.50) | 0.920 |
| MACE | 6 (11.32) | 13 (32.50) | 0.012 |
| Cardiogenic death | 1 (1.89) | 0 (0) | 0.382 |
| Non-fatal acute coronary syndrome | 4 (7.55) | 11 (27.50) | 0.010 |
| Non-fatal ischemic stroke | 0 (0) | 0 (0) | - |
| Heart failure | 1 (1.89) | 2 (5.00) | 0.400 |
Values are presented as n (%).
ICIs: immune checkpoint inhibitors; MACE: major adverse cardiovascular events.
Kaplan-Meier survival curves demonstrated no significant difference in cumulative all-cause mortality between the two groups (P = 0.911, Figure 1A). However, the cumulative incidence of MACE was significantly higher in ICIs group than in the non-ICIs group (P = 0.008, Figure 1B).
Figure 1.
Cumulative incidence of all-cause mortality and MACE. A, The cumulative incidence for the all-cause mortality; B, The cumulative incidence of the major adverse cardiovascular events. ICIs: immune checkpoint inhibitors; MACE: major adverse cardiovascular events.
Risk factors and MACE
Log-log survival plots confirmed that the PH assumption was not violated, as the curves remained parallel. To assess the correlation between HbA1c and MACE, we further analyzed patients with HbA1c ≥ 6.5%.
In univariable Cox regression analysis, patients with HbA1c ≥ 6.5% and prior treatment with VEGF inhibitors were prone to develop MACE, and ICI therapy was associated with a 3.40-fold increased overall risk of MACE (HR: 3.40, 95% CI: 1.29–8.96, P = 0.013, Table 3). After adjustment for covariates in multivariable Cox regression analysis, ICI therapy remained independently associated with an increased risk of MACE (HR: 2.86, 95% CI: 1.01–8.11, P = 0.048, Table 3).
Table 3.
Univariable and multivariable Cox proportional hazards analyses of MACE
| Parameter | Univariate analysis, hazard ratio (95% CI) | P value | Multivariate analysis, hazard ratio (95% CI) | P value |
|---|---|---|---|---|
| HbA1c ≥ 6.5% | 2.17 (0.87–5.41) | 0.096 | 1.33 (0.49–3.59) | 0.571 |
| Statins | 0.96 (0.28–3.32) | 0.945 | 0.89 (0.24–3.20) | 0.832 |
| VEGF inhibitors | 2.58 (0.86–7.80) | 0.092 | 0.67 (0.21–2.19) | 0.508 |
| ICIs therapy | 3.40 (1.29–8.96) | 0.013 | 2.86 (1.01–8.11) | 0.048 |
Covariables included age, sex, smoking, hypertension, diabetes mellitus, hyperlipidemia, coronary artery condtions, pre-treatment cardiovascular medications, and prior or concurrent anti-cancer therapy.
95% CI: 95% confidence interval; HbA1c: hemoglobin A1c; ICIs: immune checkpoint inhibitors; MACE: major adverse cardiovascular events; VEGF: vascular endothelial growth factor inhibitor.
DISCUSSION
With the acceleration of population aging, the incidence of both coronary heart disease and malignant cancer continues to rise[9–10]. CAD and cancer share numerous risk factors that may predispose patients to both conditions. Previous studies have demonstrated that the incidence of acute coronary syndrome within 6 months after a cancer diagnosis can reach up to 17%, and the risk of acute myocardial infarction in cancer patients is two to three times higher than that in non-cancer patients[11–12].
For these high-risk patients with both cancer and CAD, current management primarily focuses on the secondary prevention of coronary atherosclerosis and on selecting anti-tumor regimens with a low risk of coronary artery injury to reduce cardiovascular adverse events[13]. However, several cancer treatments are known to increase cardiac toxicity and accelerate atherosclerosis progression, resulting in a significantly higher risk of CAD among cancer survivors[14–15]. The increased risk of CAD associated with chest radiation therapy appears to be dose-dependent, beginning within five years after exposure and persisting for up to 30 years[16–17]. Among chemotherapeutic agents, fluorouracil and molecularly targeted agents are the most common causes of myocardial ischemia[18].
With the widespread clinical application of ICIs, multiple studies have reported a higher incidence of ASCVD among cancer patients receiving ICIs compared with those who did not[19–21]. In a large-scale cohort study, the rate of total aortic plaque progression was significantly higher after initiation of ICIs therapy, and the incidence of ASCVD was 4.7-fold greater in the ICIs group. Subgroup analyses revealed no differences in ASCVD risk across age, sex, body mass index, diabetes status, or tumor type, suggesting that the elevated ASCVD risk associated with ICI therapy is independent of traditional atherosclerotic risk factors[2]. However, evidence regarding the safety and efficacy of initiating ICI therapy in patients with pre-existing coronary heart disease and cancer remains limited.
We conducted a retrospective study that include cancer patients with preexisting CAD for the first time to assess the risk of adverse cardiovascular events after initiating ICIs therapy. In contrast to the non-ICIs group, the ICIs group had a considerably greater incidence of MACE. In terms of baseline medical history, cardiovascular diseases and cancer characteristics were comparable between the two groups. We observed that ICI therapy was an independent risk factor for MACE in patients with CAD and malignancies, suggesting that ICI treatment accelerates atherosclerosis progression and increases cardiovascular risk in these high-risk patients.
In the present retrospective study, we included cancer patients with pre-existing CAD to assess the risk of adverse cardiovascular events following ICI therapy. Compared with the non-ICI group, patients receiving ICIs exhibited a significantly higher incidence of MACE, despite comparable baseline cardiovascular and cancer characteristics. Our findings suggest that ICI therapy is an independent risk factor for MACE in patients with CAD and malignancy, indicating that ICIs may accelerate atherosclerosis progression and increase cardiovascular risk in these high-risk individuals.
Atherosclerosis, a lipid-mediated inflammatory process, begins with endothelial dysfunction and involves adaptive immune mechanisms that drive chronic inflammation and plaque formation[22]. The mechanisms underlying ICI-mediated atherosclerosis progression, however, remain poorly understood[23], and no human studies have directly evaluated accelerated atherosclerosis in cancer patients with CAD receiving ICIs. Mass cytometry and single-cell RNA sequencing have shown that T cells are the predominant leukocyte population within atherosclerotic plaques. Because T-cell activation aggravates atherosclerosis and PD-1–expressing T cells are present in plaques, PD-1 inhibition may reactivate these T cells and promote atherosclerosis[24–25]. Experimental studies further demonstrated aggravated atherosclerosis in mice with proprotein convertase subtilisin/kexin type 9 (PCSK9) genetic deletion or antibody inhibition, accompanied by increased infiltration of CD4+ and CD8+ T cells and macrophage activation[26]. Moreover, programmed death-ligand 1–deficient mice were found to have heightened T-cell activation and elevated production of pro-atherogenic cytokines such as interferon-γ and tumor necrosis factor-α, induced by antigen-presenting cells[27–28]. These findings collectively suggest that ICIs may contribute to atherosclerosis progression by modulating T-cell activation.
In addition, ICIs have been linked to other vascular complications, such as venous thromboembolism (VTE). Multiple studies have demonstrated an increased risk of VTE in cancer patients treated with ICIs[29–31]. Our understanding of ICI-mediated cardiovascular adverse effects remains limited, and further prospective studies are warranted to elucidate the underlying mechanisms.
Given the substantial clinical benefits of ICIs in cancer therapy, it is crucial to identify strategies that mitigate ICI-induced atherosclerosis progression and reduce cardiovascular mortality. PCSK9, a key regulator of cholesterol metabolism, downregulates cell surface low-density lipoprotein receptor (LDLR) expression by directing it toward lysosomal degradation rather than recycling[32]. In addition to its lipid-regulatory role, PCSK9 has been shown to modulate dendritic cell maturation and T-cell polarization within atherosclerotic plaques, thereby attenuating vascular inflammation. Notably, PCSK9 inhibition—via genetic deletion or monoclonal antibodies—has been shown to enhance intratumoral T-cell infiltration and improve tumor responsiveness to ICI therapy[33]. Given its dual effects in both anti-atherosclerosis and immune modulation, PCSK9 inhibition may represent a promising adjunctive therapy for patients with concurrent CAD and cancer to reduce cardiovascular events while augmenting anti-tumor efficacy.
Limitations
As a retrospective, single-center study with a relatively small sample size, this study has several limitations. The heterogeneity of tumor pathology and the challenges in accurately capturing cardiovascular endpoints events may introduce bias. Additionally, the absence of a standardized prospective cardiovascular screening protocol may have led to selection bias. Future prospective, multicenter studies with larger cohorts are needed to further evaluate the long-term cardiovascular outcomes of ICIs therapy in patients with CAD and malignancy.
CONCLUSIONS
This study is the first to observe an increased risk of MACE after ICI treatment in patients with CAD and malignancy, suggesting ICIs may serve as an independent risk factor for cardiovascular adverse events in these high-risk patients. Further prospective studies are warranted to validate these findings and clarify their clinical implications. Our study underscores the importance of comprehensive cardiovascular risk assessment before ICI initiation in patients with preexisting coronary disease. Future research should continue to explore the long-term cardiovascular impact of ICIs and identify strategies to optimize cancer therapy while minimizing cardiovascular risk.
FUNDING
This work was supported by the National Natural Science Foundation of China (No. 82170359 and No. 82470354), Noncommunicable Chronic Diseases-National Science and Technology Major Project (No. 2023ZD0502800), Shanghai Shenkang Hospital Development Center municipal hospital diagnosis and treatment technology project (No. SHDC22023207), and Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2024-JKCS-28).
AUTHOR CONTRIBUTIONS
RX is responsible for data collection and analysis, and paper writing; YW is responsible for the performance of the research and patients’ follow-up; QQC is responsible for data collection and analysis; HL is responsible for the assessment of cardiac examination results; LLC is responsible for the research design, financial support and revision of the paper.
CONFLICT OF INTEREST STATEMENT
The authors declare that they have no conflict of interest with regard to the content of this manuscript.
ACKNOWLEDGMENT
The authors thank Professor Liang Fei from Zhongshan Hospital, Fudan University, for providing statistical analysis consultation and evaluation.
DATA SHARING STATEMENT
All data generated or analyzed during this study are included in this published article.
Footnotes
Ran Xu and Yan Wang contributed equally to this work.
How to cite this article: Xu R, Wang Y, Cai QQ, Lu H, Cheng LL. Association between immune checkpoint inhibitors and adverse cardiovascular events in patients with coronary artery disease and malignant tumors: a retrospective cohort study. Cardiol Plus 2025;10:253–260. doi: 10.1097/CP9.0000000000000135.
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