Cardiovascular Health and Outcomes in Cancer Patients Receiving Immune Checkpoint Inhibitors

• Published in: The American journal of cardiology 2020-06, Vol.125 (12), p.1920-1926
• Main Authors: Oren, Ohad, Yang, Eric H., Molina, Julian R., Bailey, Kent R., Blumenthal, Roger S., Kopecky, Stephen L.
• Format: Article
• Language: English
• Subjects: Acute coronary syndromes; Age; Aspirin; Beta blockers; Cardiac arrhythmia; Cardiovascular disease; Clinical outcomes; Confidence intervals; Congestive heart failure; Diabetes; Hazards; Health hazards; Health risk assessment; Heart attacks; Heart failure; Hypercholesterolemia; Hypertension; Immune checkpoint inhibitors; Immunotherapy; Lung cancer; Melanoma; Morality; Mortality; Myocarditis; Obesity; Regression analysis; Risk factors; Statistical analysis; Stroke; Survival analysis
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2020.02.016

Whether cardiovascular (CV) disease is associated with clinical outcomes in cancer patients receiving immunotherapy is unknown. We reviewed the Mayo Clinic database for all cancer patients who received an immune checkpoint inhibitor (ICI). Multivariate logistic regression analysis, survival analyses, and Cox proportional-hazards models were formulated. Between March, 2010 and July, 2019, 3,326 patients received ICI. Mean patient age was 63.5 years (range: 16 to 96 years). In a Cox proportional-hazards model, obesity (hazard ratio [HR] 0.65, 95% confidence level [CI] 0.55 to 0.77, p < 0.001) and hypercholesterolemia (HR 0.80, 95% CI 0.72 to 0.89, p < 0.001) were associated with lower all-cause mortality while hypertension (HR 1.32, 95% CI 1.17 to 1.49, p < 0.001) and smoking (HR 1.17, 95% CI 1.06 to 1.29, p = 0.002) were associated with higher overall mortality. Among patients with lung cancer, multivariable-adjusted hazard ratios for death from any cause for beta blocker users, as compared with patients who had never used a beta blocker, were 1.39 (95% CI 1.10 to 1.76, p = 0.006). A total of 80 patients (2.4%) experienced CV immune-related adverse events. Event-related morality for ICI-induced myocarditis was 41.7% (5/12). Multivariable-adjusted hazard ratios for ICI-induced myocarditis were 5.2 (95% CI 1.4 to 18.7, p = 0.01) for history of heart failure, 4.06 (95% CI 1.15 to 14.3, p = 0.03) for history of acute coronary syndrome, and 1.07 (per each 1-year increase, 95% CI 1.01 to 1.14, p = 0.02) for age. In conclusion, our study shows that CV factors are associated with clinical outcomes in cancer patients receiving ICI and could be used to predict mortality. In patients with lung cancer, pretreatment beta blocker use is associated with higher all-cause mortality. Three clinical factors—history of heart failure, history of acute coronary syndrome, and age greater than 80 years—help identify patients at higher risk of ICI-induced myocarditis who might benefit from more intensive cardiac surveillance.