Table 3.
Summary of Clinical Studies of ICI Therapy and Atherosclerotic CV Events
| First Author (Year) | Study | Sample | Design/Findings | Main ICI Effect |
|---|---|---|---|---|
| Hu et al (2017)76 | Meta-analysis (22 studies) | 4,828 | 1.0% incidence of MI (95% CI: 0%-3.8%) and 2.0% of stroke (95% CI: 0%-13.0%) | ↓ ASCVD rate |
| Gelsomino et al (2018)68 | Single-center observational | 38 | 29% (n = 11) patients with plaques; 27.3% decreased, 63.6% had no changes, 9.1% had plaque progression post-ICIs | ↓ Plaque burden |
| Salem et al (2018)11 | Multicenter registry (Vigibase) | 31,321 irAEs | Incidence of MI was 0.53%, and cerebral arterial ischemia was 0.62%, similar to non-ICI patients. | ↓ ASCVD rate |
| Newman et al (2019)75 | Single center Comparative |
22 | Autopsy-based: no difference in plaque burden between matched control subjects and post-ICI patients but higher ratio of CD3+ T cells to CD68+ macrophages in post-ICI plaques | = Plaque burden ↑ CD3+/CD68+ |
| Nichetti et al (2020)156 | Post hoc prospective observational | 217 | 6.5% incidence of acute vascular events (2 ACS, 9 strokes, 3 visceral arterial thromboses) within 16 mo | ↑ ASCVD rate |
| Chitturi et al (2019)71 | Single center Retrospective |
252 | 135 post-ICI: 37.8% incidence of CV irAEs; no increase in MACE (CV death, MI, stroke, or HF hospitalization) post-ICIs within 6 mo (HR: 1.2; 95% CI: 0.6-2.4; P = 0.66); pretreatment or combined ICI and VEGFIs or TKIs had an increased risk of MACE (HR: 2.15; 95% CI: 1.05-4.37; P = 0.04) | No increase ASCVD |
| Wang et al (2019)32 | Meta-analysis (125 studies) | 20,128 | 9.8% incidence of treatment-related deaths due to CV irAEs, including MI, HF, and CM | ↑ ASCVD rate |
| Bar et al (2019)72 | Single center Retrospective |
1,215 | Single cohort: acute vascular events within 6 mo post-ICIs: 2.6% (95% CI: 1.8%-3.6%); event rate was 5.2% (95% CI: 2.8%-9.2%); acute vascular events incidence higher within 6 mo (OR: 3.49; 95% CI: 1.45-8.41; P = 0.002). 1% of cases were MI or ischemic stroke. OS worse in post-ICI patients with acute vascular events (3 mo vs 14 mo; HR: 3.01; 95% CI: 2.07-4.39; P < 0.0001). |
↑ ASCVD |
| Drobni et al (2020)31 | Single center Retrospective |
5,684 | Matched cohort, case crossover, and imaging study: higher risk of acute vascular events in ICIs (HR: 3.3; 95% CI: 2.0-5.5; P < 0.001) Case crossover: higher incidence of acute vascular events at 2 years after ICIs vs 2 years before ICIs (adjusted HR: 4.8; 95% CI: 3.6-6.5; P < 0.001) Imaging: Higher aortic plaque progression rate (2.1%/y before ICIs to 6.7%/y after ICIs) |
↑ Plaque ↑ ASCVD |
| Oren et al (2020)79 | Single center Retrospective |
3,326 | Rate of MI was 213 (7%) and stroke was 227 (7%) patients | ↑ ASCVD rate |
| Nso et al (2020)77 | Meta-analysis (26 studies) | 4,622 | 0.4% incidence of MI (95% CI: 0.1%-0.8%) | ↓ ASCVD rate |
| Solinas et al (2020)78 | Meta-analysis (68 studies) | 20,273 | Incidence of arterial thromboembolism 1.1% (95% CI: 0.5%-2.1%), stroke 1.1% (95% CI: 0.65%-1.45%), and MI 0.7% (95% CI: 0.15%-1.15%) | ↓ ASCVD rate |
| Dolladille et al (2021)81 | Meta-analysis (63 studies) | 32,528 | Incidence of MI was 7.4 (95% CI: 6.0-9.1) and cerebral ischemia was 8.8 (95% CI: 7.2-10.7) per 1,000 patients; ICIs significantly increased the risk of MI (OR: 1.51) and cerebral arterial ischemia (OR: 1.56) compared with control subjects | ↑ ASCVD rate |
| D'Souza et al (2021)80 | Multicenter registry (Danish) | 1,100 | 9.7% increased risk of CV irAEs (myocarditis, HF, arrhythmias, pericarditis, or CV death in 6 y | ↑ ASCVD rate |
| Laenens et al (2022)12 | Single center Retrospective |
672 | Matched cohort: 10.3% incidence of CV irAEs (MI, HF, and cerebral ischemia) with an overall mortality of 54.9% and a CV death rate of 1.9% over 13 mo | ↑ ASCVD rate |
ACS = acute coronary syndrome; ASCVD = atherosclerotic cardiovascular disease; CM = cardiomyopathy; CV = cardiovascular; HF = heart failure; ICI = immune checkpoint inhibitor; irAE = immune-related adverse event; MACE = major cardiovascular events; MI = myocardial infarction; OS = overall survival; TIA = transient ischemic attack; TKI = tyrosine kinase inhibitor; VEGFI = vascular endothelial growth factor inhibitor.