Immune checkpoint inhibitors linked to increased major cardiac events in the real world

12 Jul 2022 byKanas Chan
Immune checkpoint inhibitors linked to increased major cardiac events in the real world
Treatment with immune checkpoint inhibitors (ICIs) in real-world settings is associated with a higher incidence of adverse cardiovascular events than traditionally reported in clinical trials, a retrospective cohort study has shown. Patients at risk include those with a history of cardiovascular disease (CVD), especially a history of heart failure (HF) or valvular heart disease (VHD).

“In rare cases, ICIs cause immune-mediated myocarditis. However, the true incidence of other major adverse cardiovascular events [MACEs; ie, acute coronary syndrome (ACS), HF, stroke, and transient ischaemic attack (TIA)] after ICI treatment remains unknown, because late-occurring side effects are rarely reported in prospective clinical trials … and current literature on cardiovascular toxicity of ICIs consists mainly of case series,” wrote the researchers. [J Clin Oncol 2022:doi:10.1200/JCO.21.01808]

To identify the incidence and risk factors of MACEs in ICI-treated patients, 672 cancer patients treated with ICIs (full ICI cohort; mean age, 64.8 years; male, 64.7 percent; history of CVD, 20.5 percent) were included in the study.

During a median follow-up of 13 months, MACEs occurred in 10.3 percent of ICI-treated cancer patients, with a median time to event of 5 months and a high total mortality rate of 54.9 percent, but a low cardiovascular death rate of 1.9 percent.

“A history of HF or VHD increased the vulnerability of ICI-treated patients to MACE,” highlighted the researchers. History of HF was associated with a twofold higher risk of MACEs (HR, 2.27; 95 percent CI, 1.03–5.04; p=0.043), while history of VHD was associated with a threefold higher risk of MACEs (HR, 3.01; 95 percent CI, 1.05–8.66; p=0.041), according to multivariable analysis.

In secondary outcome analysis, smoking history (HR, 5.18; 95 percent CI, 1.09–24.70; p=0.039) and previous treatment with VEGF inhibitors (HR, 3.74; 95 percent CI, 1.29–10.88; p=0.016) were independently associated with ACS. Furthermore, history of HF and VHD were both associated with a threefold higher risk of HF (history of HF: HR, 3.42; 95 percent CI, 1.48–7.92; p=0.004) (history of VHD: HR, 3.76; 95 percent CI, 1.26–11.22; p=0.017).

After adjusting for age (± 5 years), sex, and history of CVD, the incidence of MACEs in the ICI cohort (n=421; mean age, 65.4 years; male, 70.8 percent; history of CVD, 22.8 percent) was compared with the incidence in two matched cohorts, including cancer patients without exposure to ICIs (positive controls; n=396) and individuals without a history of cancer (negative controls; n=399).

“In patients treated with ICIs, incidence rates of MACEs were significantly [higher than] both control groups,” reported the researchers.

Results of the study showed a significantly lower risk of MACEs in the non-ICI group (HR, 0.61; 95 percent CI, 0.38–0.99; p=0.047) and in individuals without a history of cancer (HR, 0.24; 95 percent CI, 0.15–0.037; p<0.001). “This suggests a potential harmful effect of ICI treatment besides the underlying risk profile,” the researchers noted. “A modest, although statistically nonsignificant overweight of HF events [was] likely responsible for these findings.”

“Our data highlight the clinical relevance of cardiovascular work-up in patients with cancer before exposure to ICI treatment, particularly in those with pre-existing CVD,” recommended the researchers. “A routine thorough cardiovascular history, electrocardiography, and echocardiography might identify patients who need regular cardiovascular follow-up during and after ICI treatment.”