Atherosclerosis With Immune Checkpoint Inhibitor Therapy

Suero-Abreu, Giselle Alexandra; Zanni, Markella V.; Neilan, Tomas G.

doi:10.1016/j.jaccao.2022.11.011

Cited by 44 publications

(18 citation statements)

References 156 publications

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“…Vascular inflammation is a well-known contributor to atherosclerosis and heart failure with preserved ejection fraction. Accordingly, recent clinical data has shown a three-fold higher risk of CV events after ICI initiation, as well as a three-fold higher rate of progression of total aortic plaque volume, thus suggesting that CV irAEs could be mediated by an accelerated progression of atherosclerosis [8,[13][14][15][16][17][18][19][20][21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study

et al. 2023

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Background: The increasing use of immune checkpoint inhibitors (ICIs) in the treatment of both advanced and early stages of various malignancies has resulted in a substantial increase in the incidence of cardiovascular (CV) immune-related adverse events (irAEs). The current follow-up guidelines are based on anecdotal evidence and expert opinions, due to a lack of solid data and prospective studies. As many questions remain unanswered, cardiac monitoring, in patients receiving ICIs, is not always implemented by oncologists. Hence, an urgent need to investigate the possible short- and long-term CV effects of ICIs, as ICI approval is continuing to expand to the (neo)adjuvant setting. Methods: We have initiated a prospective, multicenter study, i.e., the CAVACI trial, in which a minimum of 276 patients with a solid tumor, eligible for ICI treatment, will be enrolled. The study consists of routine investigations of blood parameters (troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, in particular) and a thorough CV follow-up (electrocardiograms, transthoracic echocardiograms, and coronary calcium scoring) at fixed time points for a total period of two years. The primary endpoint is the cumulative incidence of troponin elevation in the first three months of ICI treatment, compared to baseline levels. Furthermore, secondary endpoints include incidence above the upper limit of normal of both troponin and NT-proBNP levels, evolution in troponin and NT-proBNP levels, the incidence of CV abnormalities/major adverse cardiac events, evaluation of associations between patient characteristics/biochemical parameters and CV events, transthoracic echocardiography parameters, electrocardiography parameters, and progression of coronary atherosclerosis. Recruitment of patients started in January 2022. Enrolment is ongoing in AZ Maria Middelares, Antwerp University Hospital, AZ Sint-Vincentius Deinze, and AZ Sint-Elisabeth Zottegem. Trial registration: ClinicalTrials.gov Identifier: NCT05699915, registered 26 January 2023.

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Section: Introductionmentioning

confidence: 99%

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study

et al. 2023

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“…Specific chemotherapies such as immune checkpoint inhibitors, anti-HER2 antibodies, VEGF inhibitors, and MEK inhibitors have been suggested to cause myocardial damage. [30][31][32][33][34] Previous studies also report that immune checkpoint inhibitors are associated with progression of atherosclerosis. 30,33-34 Although the mechanism is not fully understood, it is thought that immune checkpoint inhibitors target proteins that negatively regulate atherosclerosis, thereby accelerating atherosclerosis among patients with a history of cancer.…”

Section: Discussionmentioning

confidence: 98%

“…30,33-34 Although the mechanism is not fully understood, it is thought that immune checkpoint inhibitors target proteins that negatively regulate atherosclerosis, thereby accelerating atherosclerosis among patients with a history of cancer. 33 In the present study, 1 patient was treated with molecular-targeted therapy (Supplementary Table 3), but the limited number of patients in the cancer group did not allow us to examine the effect of each type of chemotherapy on CV events. Further studies are needed to elucidate the effect of these chemotherapies on CV events among patients with AMI who undergo revascularization.…”

Section: Discussionmentioning

confidence: 98%

Impact of a Cancer History on Cardiovascular Events Among Patients With Myocardial Infarction Who Received Revascularization

Takeuchi

Kosugi

Ueda

et al. 2024

Circ J

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Background: It remains controversial whether a cancer history increases the risk of cardiovascular (CV) events among patients with myocardial infarction (MI) who undergo revascularization. Methods and Results:Patients who were confirmed as type 1 acute MI (AMI) by coronary angiography were retrospectively analyzed. Patients who died in hospital or those not undergoing revascularization were excluded. Patients with a cancer history were compared with those without it. A cancer history was examined in the in-hospital cancer registry. The primary outcome was a composite of cardiac death, recurrent type 1 MI, post-discharge coronary revascularization, heart failure hospitalization, and stroke. Among 551 AMI patients, 55 had a cancer history (cancer group) and 496 did not (non-cancer group). Cox proportional hazards model revealed that the risk of composite endpoint was significantly higher in the cancer group than in the non-cancer group (adjusted hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.13-2.82). Among the cancer group, patients who were diagnosed as AMI within 6 months after the cancer diagnosis had a higher risk of the composite endpoint than those who were diagnosed as AMI 6 months or later after the cancer diagnosis (adjusted HR: 5.43; 95% CI: 1.55-19.07). Conclusions:A cancer history increased the risk of CV events after discharge among AMI patients after revascularization.

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“…In a sub-study, the progression of aortic plaque size was found to be three times higher under ICI therapy. Prospective studies will be essential in determining the reproducibility of such associations [ 55 , 56 ].…”

Section: Coronary Artery Disease and Acute Myocardial Infarctionmentioning

confidence: 99%

Cellular Alterations in Immune Checkpoint Inhibitor Therapy-Related Cardiac Dysfunction

Michel,

Ferdinandy,

Rassaf

2024

Curr Heart Fail Rep

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Purpose of Review Immune checkpoint inhibitor (ICI) therapy has emerged as a pivotal advancement in cancer treatment, but the widespread adoption has given rise to a growing number of reports detailing significant cardiovascular toxicity. This review concentrates on elucidating the mechanisms behind ICI-related cardiovascular complications, emphasizing preclinical and mechanistic data. Recent Findings Accumulating evidence indicates a more significant role of immune checkpoints in maintaining cardiac integrity than previously understood, and new key scientific data are available to improve our understanding of ICI-related cardiovascular toxicity, including hidden cardiotoxicity. New avenues for innovative concepts are hypothesized, and opportunities to leverage the knowledge from ICI-therapy for pioneering approaches in related scientific domains can be derived from the latest scientific projects. Summary Cardiotoxicity from ICI therapy is a paramount challenge for cardio-oncology. Understanding the underlying effects builds the foundation for tailored cardioprotective approaches in the growing collective at risk for severe cardiovascular complications.

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Atherosclerosis With Immune Checkpoint Inhibitor Therapy

Cited by 44 publications

References 156 publications

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study

Impact of a Cancer History on Cardiovascular Events Among Patients With Myocardial Infarction Who Received Revascularization

Cellular Alterations in Immune Checkpoint Inhibitor Therapy-Related Cardiac Dysfunction

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