Immune checkpoint inhibitor therapy linked to higher incidence of cardiovascular events

Immune checkpoint inhibitor therapy appeared associated with an increased risk for major adverse cardiovascular events among patients with cancer and a prior history of cardiovascular disease, according to results of a retrospective study.

The findings, published in Journal of Clinical Oncology, suggest routine thorough cardiovascular history, electrocardiography and echocardiography might identify patients who need regular cardiovascular follow-up during and after immune checkpoint inhibitor treatment, researchers noted.

Background

Immune checkpoint inhibitors (ICIs) have been known to cause immune-mediated myocarditis in some patients. However, incidence of other major adverse cardiovascular events after ICI therapy remains unknown, according to study background.

“The current literature on cardiovascular toxicity of ICIs consists mainly of case series,” Dorien Laenens, MD, cardiologist in the department of cardiology at University Hospitals Leuven in Belgium, and colleagues wrote. “Another limitation of the currently available data is that randomized clinical trials of ICIs focus on survival, response and disease control, usually [during] short follow-up periods.”

To address the lack of knowledge, researchers collected data from digital patient files of University Hospitals to identify incidence of and risk factors for major adverse cardiovascular events among 672 patients (median age, 65 years; 64.7% men) with cancer treated with ICIs, and compared incidence rates with patients with cancer not treated with ICIs and population controls after matching according to age, sex, cardiovascular history and cancer type.

Major adverse cardiovascular events — a composite of acute coronary syndrome, heart failure, stroke and transient ischemic attack — served as the primary endpoint. Acute coronary syndrome and heart failure served as secondary outcomes.

Median follow-up was 13 months (interquartile range, 6-22).

Findings

Overall, 572 patients received only one line of ICI therapy, 90 patients received two lines of therapy, eight patients received three lines and two patients received four lines. More than half of patients (54.9%) died — with 1.9% deemed cardiovascular deaths.

Researchers reported a 10.3% incidence of major cardiovascular events, with a median time to event of 5 months.

Results of multivariable analysis showed having a history of heart failure (HR = 2.27; 95% CI, 1.03-5.04) and valvular heart disease (HR = 3.01; 95% CI, 1.05-8.66) remained significantly associated with major adverse cardiovascular events.

“Cumulative incidence rates were significantly higher in the ICI group compared with the cancer cohort not exposed to ICI and the population controls, mainly driven by a higher risk of heart failure events,” the researchers wrote.

Implications

The findings reinforce the clinical relevance of a cardiovascular workup of patients with cancer before exposure to ICI treatment, particularly in those with preexisting cardiovascular disease, the researchers wrote.

“Prospective or retrospective all-comer studies with bigger cohorts are essential for capturing true incidence of major cardiac events in daily practice,” they continued.

“Concomitant cardiovascular disease is often an exclusion criterion in clinical trials. This might be one of the reasons why this type of toxicity is underreported in phase 3 trials. In addition, toxicity is often not part of the follow-up when treatment within the context of the study is ceased. Cohort studies like ours can compensate for these shortcomings.”