Cardiovascular and venous thromboembolism risks in cancer patients treated with immune checkpoint inhibitors compared to non-users- a multi-center retrospective study

Abstract

Background: Immune Checkpoint Inhibitors (ICIs) have revolutionized cancer therapy. This study examines the cardiovascular risks of ICIs compared to non-ICI therapies.

Methods: Utilizing the Chang Gung Research Database (CGRD) of Taiwan, this retrospective study analyzed 188,225 cancer patients, with 1,737 undergoing ICI treatment from January 1, 2008, to June 30, 2021. Through 1:1 propensity score matching (PSM), we compared specific outcomes between patients treated with ICIs and those who were not. The analysis also accounted for the competing risk of mortality in assessing the results after PSM. The observation period spanned from this index date to whichever came first: the date of the specific outcomes, the last follow-up recorded, or the end date of the study on June 30, 2022.

Results: The study found no significant increase in the risk of cardiac death, non-fatal myocardial infarction, heart failure hospitalization, deep vein thrombosis, or pulmonary embolism in patients treated with ICIs as compared to those receiving non-ICI therapy. Interestingly, ICI treatment was linked to a lower risk of non-fatal stroke (0.27% per year vs. 0.46% per year; subdistribution hazard ratio = 0.59; 95% confidence interval = 0.35-0.98; P = 0.0430). Furthermore, subgroup analysis revealed that the ICI group had a decreased risk of cardiac death in patients with cancers other than head and neck cancer, and a reduced risk of stroke among diabetic patients.

Conclusions: ICIs do not significantly elevate the risk of cardiovascular events in cancer patients and may lower the stroke risk, underscoring the need for additional prospective studies to clarify these findings.

Keywords: Cancer; Deep vein thrombosis; Heart failure; Immune checkpoint inhibitor; Myocardial infarction; Pulmonary embolism; Stroke.

Fig. 1

Enrollment of Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy Compared to Those on Non-Immune Checkpoint Inhibitor Therapy Between January 1, 2008, and June 30, 2022, after excluding individuals younger than 18 years old or those without follow-up data, we initially identified 188,225 cancer patients, of which 1,737 had undergone ICI treatment and 186,488 had not. After propensity score matching (PSM), we included 1,714 patients in the ICI treatment group and an equal number in the non-ICI treatment group for comparative analysis Abbreviations: ICI = immune checkpoint inhibitor

Fig. 2

Cumulative Incidence Curves for Cardiovascular Outcomes in Cancer Patients: Comparing Immune Checkpoint Inhibitor Therapy to Non-Immune Checkpoint Inhibitor Therapy After Propensity Score Matching Cumulative incidence curves of specific outcomes for cancer patients are depicted in Fig. 2. The outcomes examined include (A) Cardiac death, (B) Non-fatal MI, (C) Non-fatal stroke, and (D) HFH. The study show that ICI group exhibited comparable cumulative risks of cardiac death, non-fatal MI, and HFH compared to the non-ICI group. ICI group demonstrated a lower annual event rate of non-fatal stroke in the ICI group compared to the non-ICI group Abbreviations: HFH = heart failure hospitalization; ICI = immune checkpoint inhibitor; MI = myocardial infarction

Fig. 3

Cumulative Incidence Curves for Deep Vein Thrombosis and Pulmonary Embolism in Cancer Patients: Comparing Immune Checkpoint Inhibitor Therapy to Non-Immune Checkpoint Inhibitor Therapy After Propensity Score Matching Cumulative incidence curves of specific outcomes for cancer patients are depicted in Fig. 3. The outcomes examined include (A) DVT and (B) PE. The study show that ICI group exhibited comparable cumulative risks of DVT and PE compared to the non-ICI group Abbreviations: DVT = deep vein thrombosis; ICI = immune checkpoint inhibitor; PE = pulmonary embolism