Anti-CTLA-4 therapy increased the risk of heart failure (HR 1.9; 95% CI 1.27-2.84) and stroke (HR 1.7; 95% CI 1.3-2.22) compared to anti-PD-1 therapy in patients receiving immune checkpoint inhibitors.
Cohort (n=33,148)
Yes
Does immune checkpoint inhibitor therapy increase the risk of cardiovascular adverse events in patients with cancer?
Real-world data demonstrates a significant incidence of cardiovascular adverse events with immune checkpoint inhibitors, particularly highlighting increased risks of heart failure and stroke with anti-CTLA-4 therapy.
BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause life-threatening cardiovascular adverse events (CVAEs) that may not be attributed to therapy. The outcomes of clinical trials may underestimate treatment-related adverse events due to restrictive eligibility, limited sample size, and failure to anticipate selected toxicities. We evaluated the incidence and clinical determinants of CVAEs in real-world population on ICI therapy. PATIENTS AND METHODS: Among 2 687 301 patients diagnosed with cancer from 2011 to 2018, 16 574 received ICIs for any cancer. Patients in the ICI and non-ICI cohorts were matched in a 1 : 1 ratio according to age, sex, National Cancer Institute comorbidity score, and primary cancer. The non-ICI cohort was stratified into patients who received chemotherapy (N = 2875) or targeted agents (N = 4611). All CVAEs, non-cardiac immune-related adverse events occurring after treatment initiation, baseline comorbidities, and treatment details were identified and analyzed using diagnosis and billing codes. RESULTS: Median age was 61 and 65 years in the ICI and non-ICI cohorts, respectively (P < 0.001). ICI patients were predominantly male (P < 0.001). Lung cancer (43.1%), melanoma (30.4%), and renal cell carcinoma (9.9%) were the most common cancer types. CVAE diagnoses in our dataset by incidence proportion (ICI cohort) were stroke (4.6%), heart failure (3.5%), atrial fibrillation (2.1%), conduction disorders (1.5%), myocardial infarction (0.9%), myocarditis (0.05%), vasculitis (0.05%), and pericarditis (0.2%). Anti-cytotoxic T-lymphocyte-associated protein 4 increased the risk of heart failure versus anti-programmed cell death protein 1; hazard ratio (HR), 1.9; 95% confidence interval (CI) 1.27-2.84 and stroke (HR, 1.7; 95% CI 1.3-2.22). Pneumonitis was associated with heart failure (HR, 2.61; 95% CI 1.23-5.52) and encephalitis with conduction disorders (HR, 4.35; 95% CI 1.6-11.87) in patients on ICIs. Advanced age, primary cancer, nephritis, and anti-cytotoxic T-lymphocyte-associated protein 4 therapy were commonly associated with CVAEs in the adjusted Cox proportional hazards model. CONCLUSIONS: Our findings underscore the importance of risk stratification and cardiovascular monitoring for patients on ICI therapy.
Jain et al. (Fri,) conducted a cohort in Cancer (n=33,148). Immune checkpoint inhibitors (ICIs) vs. Non-ICI therapy (chemotherapy or targeted agents) was evaluated on Cardiovascular adverse events (CVAEs). Anti-CTLA-4 therapy increased the risk of heart failure (HR 1.9; 95% CI 1.27-2.84) and stroke (HR 1.7; 95% CI 1.3-2.22) compared to anti-PD-1 therapy in patients receiving immune checkpoint inhibitors.