Cardiovascular events after the initiation of immune checkpoint inhibitors

Yuta Suzuki; Hidehiro Kaneko; Yuichi Tamura; Akira Okada; Katsuhito Fujiu; Nobuaki Michihata; Norifumi Takeda; Taisuke Jo; Hiroyuki Morita; Koichi Node; Hideo Yasunaga; Issei Komuro

doi:10.1016/j.heliyon.2023.e16373

Cardiovascular events after the initiation of immune checkpoint inhibitors

Heliyon. 2023 May 18;9(5):e16373. doi: 10.1016/j.heliyon.2023.e16373. eCollection 2023 May.

Authors

Yuta Suzuki^{1

2}, Hidehiro Kaneko^{1

3}, Yuichi Tamura⁴, Akira Okada⁵, Katsuhito Fujiu^{1

3}, Nobuaki Michihata⁶, Norifumi Takeda¹, Taisuke Jo⁶, Hiroyuki Morita¹, Koichi Node⁷, Hideo Yasunaga⁸, Issei Komuro¹

Affiliations

¹ The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.
² Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health, Saitama, Japan.
³ The Department of Advanced Cardiology, The University of Tokyo, Tokyo, Japan.
⁴ Department of Cardiology, International University of Health and Welfare School of Medicine, Narita, Japan.
⁵ Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁶ The Department of Health Services Research, The University of Tokyo, Tokyo, Japan.
⁷ Department of Cardiovascular Medicine, Saga University, Saga, Japan.
⁸ The Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan.

Abstract

We sought to clarify the incidence of major adverse cardiac events (MACE) after the initiation of immune checkpoint inhibitors (ICIs). We analyzed the JMDC Claims Database between 2005 and 2021. The study included 2972 patients with no history of cardiovascular disease and a prescription for an ICI. The primary outcome was the incidence of MACE, including myocarditis, pericarditis, Takotsubo cardiomyopathy, atrio-ventricular block, heart failure, myocardial infarction, and stroke. The median age of study participants was 59 (Q1-Q3 53-65) years, and 2163 participants (72.8%) were male. Lung cancer was the most common cancer site (n = 1603). Among ICIs, programmed cell death-1 (PD-1) was most frequently used, and a combination ICI treatment was conducted in 110 patients (3.7%). During a mean follow-up of 358 ± 327 days, 419 MACE events were recorded. The incidence rate of myocarditis, pericarditis, Takotsubo cardiomyopathy, atrio-ventricular block, heart failure, myocardial infarction, and stroke was 3.4, 142.3, 10.3, 17.2, 1191.2, 55.2, and 278.5 per 10,000 person-years, respectively. The incidence of cardiovascular events was higher within 180 days after the initial prescription of ICI. The continuation rate of ICI after MACE was 38.4%. In conclusion, our analysis of a nationwide epidemiological dataset demonstrated the incidence of MACE after the initiation of ICI treatment. The incidence of heart failure was higher than expected, and the continuation rate of ICI treatment after MACE was low. Our results indicated the importance of monitoring and prevention of cardiovascular events in cancer patients requiring ICI treatment.

Keywords: Cancer; Cardiovascular disease; Immune checkpoint inhibitors; Immune-related adverse events.