Log in to MyACC
Immune Checkpoint Inhibitors, Atherosclerosis, and Cardiovascular Events
Quick Takes
- Targets of immune checkpoint inhibitors (ICI) (PD-1, PD-L1, and CTLA-4) are negative regulators of atherosclerosis.
- Use of ICI is associated with a threefold higher risk of cardiovascular events including myocardial infarction, need for revascularization, and stroke, and progress of atherosclerosis.
- Aggressive optimization of cardiovascular risk factors and medical therapy for primary or secondary prevention of cardiovascular disease is warranted in patients on ICI.
Study Questions:
Are immune checkpoint inhibitors (ICI) associated with an increased risk of cardiovascular events and accelerated atherosclerosis?
Methods:
In this single-center matched cohort study, 2,842 patients with cancer treated with ICI were matched to 2,842 with cancer but who never received ICI according to age, history of cardiovascular event, and cancer type, using the first visit as the study entry point for controls. The authors also performed a case-crossover study, with the interval 2 years prior to ICI initiation as the observation period and the 2-year interval after the start of ICI as the at-risk period. The primary outcome was the occurrence of a cardiovascular event, defined as a composite of myocardial infarction, coronary revascularization, and ischemic stroke. In a substudy with 40 patients with melanoma, serial thoracic aorta plaque volume was measured from imaging studies obtained as part of clinical care to assess the rate of atherosclerosis pre- and post-ICI.
Results:
Overall, the median age of the cohort was 66 years, and consisted of 55% men and >90% white. At least 10% of patients had a prior cardiovascular event. Non–small cell lung cancer (28.8%) and melanoma (27.9%) were the most common type of cancer. Among ICI recipients, PD-1 inhibitor was the most commonly prescribed therapy, and 43.2% had an immune-related adverse event. Overall, 119 (4.2%) patients in the ICI group experienced a cardiovascular event (58 with myocardial infarction, 36 requiring coronary revascularization, and 45 with ischemic stroke). In multivariable analysis, use of an ICI was associated with a threefold increase in the risk of cardiovascular events (adjusted hazard ratio, 3.3; 95% confidence interval, 2.0-5.5). In the crossover study, 66 (2.32%) patients had a cardiovascular event prior to starting an ICI, and 119 (4.2%) after initiation of ICI. In the substudy of 40 patients with melanoma who underwent repeated imaging, there was a significant increase in total and noncalcified plaque volume. Patients on statin had a reduced progression rate of plaque volume.
Conclusions:
ICI are associated with a threefold increase risk of cardiovascular events and a higher rate of aortic plaque progression.
Perspective:
The indications for immune checkpoint inhibitors are broadening and their use as the preferred anticancer therapies for many types of malignancies is increasing exponentially. Research on cardiotoxicity related to ICI has focused on myocarditis as an immune-related adverse event. This study, on the other hand, lends credence to the hypothesis that ICI could impact atherosclerosis through inhibiting the PD-1/PD-L1 pathways, known to down-regulate the proatherogenic T-cell response. The analytical approach, which attempts to compensate for some of the limitations afforded by the retrospective nature of the study, lends credence to the main findings. The increased risk of cardiovascular events with ICI does not outweigh their overwhelming cancer-related benefits but focuses the attention on the aggressive management of comorbid cardiovascular risk factors or disease in candidates for ICI therapy.
Clinical Topics: Cardiac Surgery, Cardio-Oncology, Cardiovascular Care Team, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Nonstatins, Novel Agents, Statins, Interventions and Imaging
Keywords: Aorta, Thoracic, Atherosclerosis, Brain Ischemia, Carcinoma, Non-Small-Cell Lung, Cardiotoxicity, Diagnostic Imaging, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lung Neoplasms, Myocardial Infarction, Myocardial Revascularization, Myocarditis, Neoplasms, Plaque, Atherosclerotic, Secondary Prevention, Stroke, T-Lymphocytes, Vascular Diseases
< Back to Listings
