Immune checkpoint inhibitors and the risk of major atherosclerotic cardiovascular events in patients with high-risk or advanced melanoma: a retrospective cohort study

Abstract

Background Immune checkpoint inhibitors (ICI) are associated with immune-mediated adverse effects, potentially involving any organ. ICI has also been associated with an increased risk of cardiovascular disease in cancer populations. Objective To characterize the incidence and risk of major atherosclerotic cardiovascular events associated with ICI use in a high-risk and advanced melanoma population. Methods We conducted a retrospective cohort study of patients with high-risk or advanced melanoma (AJCC stage II, III or IV) presenting to an academic tertiary hospital between 2015–2020. The main outcome was major atherosclerotic cardiovascular events (MACE) including acute myocardial infarction, ischemic stroke, acute limb ischemia and coronary revascularization. Results The study cohort consisted of 646 patients, including 289 who had been treated with ICI. The incidence of MACE was higher in the ICI treated group (3.6 vs. 0.9 events per 100-person years). After adjusting for age, sex, smoking history and prior BRAF and/or MEK inhibitor use, ICI treatment was associated with an increased risk of MACE (HRadj 2.8, 95% CI 1.1–6.9, p = 0.03). Elevated risk was especially pronounced in patients with a past history of MACE (HR 14.4, 95% CI 1.9–112.3, p = 0.01). Conclusion Patients with high-risk or advanced melanoma are at an increased risk of atherosclerotic cardiovascular events following ICI treatment, particularly those with a history of cardiovascular disease.

Immune checkpoint inhibitors in cancer: the increased risk of atherosclerotic cardiovascular disease events and progression of coronary artery calcium

“…For example, Drobni et al [ 14 ] found that the risk of myocardial infarction, coronary revascularization, and ischemic stroke increased at varying degrees after the use of ICIs, and that total aortic plaque volume also showed a simultaneous increase. Similar findings were found in the melanoma patient cohort studied by Wang et al [ 15 ]. In the study by Schiffer et al [ 16 ], patients treated with ICIs who had cardiovascular events had worse baseline coronary and aortic calcification.…”

“…In 2020, Drobni et al [ 14 ] first reported that ICIs were highly associated with atherosclerotic cardiovascular events. Recently, Wang et al [ 15 ] found an increased risk of ASCVD events in patients with high-risk or advanced melanoma after ICI therapy. Similar conclusions have been reached in a cohort of patients with NSCLC.…”

Immune Checkpoint Inhibitors and Cardiotoxicity: A Comparative Meta‐Analysis of Observational Studies and Randomized Controlled Trials

“…In the OSs, our results show that ICI use was not associated with increased risk of myocarditis ( P =0.09) or pericardial disease ( P =0.19, Figure 6 , 14 , 17 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ). However, the use of combination ICIs was associated with higher risk of myocarditis (OR, 3.07 [95% CI, =1.28–7.39], P <0.02) but not pericardial disease (OR, 4.13 [95% CI, 0.19–89.86], P <0.67) compared with single ICI therapy in OSs.…”

“… Forest plot of included OSs, separated based on therapy comparisons for myocarditis 14 , 17 , 53 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ( A ) and pericardial disease 17 , 53 , 54 , 55 , 56 ( B ). The squares and horizontal lines correspond to the study‐specific ORs and 95% CIs.…”

Shaping the Future of Cardiac Wellness: Exploring Revolutionary Approaches in Disease Management and Prevention

“…Clinical trials have shown that monoclonal antibodies targeting these molecules can improve outcomes for patients with cardiovascular diseases. Adoptive cell transfer involves the transfer of immune cells that have been genetically engineered to target specific disease-causing agents [131]. For example, T cells can be engineered to target and destroy cells that contribute to atherosclerosis.…”