Association between immune checkpoint inhibitors and cardiovascular risks: a nationwide self-controlled case series study

Abstract

Immune checkpoint inhibitors (ICIs) are widely used for cancer treatment but are linked to potential cardiotoxicity. The time-dependent effects of ICIs on cardiovascular outcomes remain unclear. This study explores associations between ICI use and cardiovascular events. This self-controlled case series (SCCS) analyzed cancer patients who received ICIs from January 2019 to December 2020 using the National Health Insurance Research Database (NHIRD). Exposure periods were defined as the duration of ICI prescriptions plus 90 days. Poisson regression estimated incidence rate ratios (IRRs) for heart failure (primary outcome) and arterial events or perimyocarditis (secondary outcomes) during and after ICI exposure compared to baseline. Among 1,146 ICI users, 15 developed heart failure, 33 experienced arterial events, and 11 had perimyocarditis. Cardiovascular events were uncommon but showed elevated risks for heart failure (IRR: 7.73; CI: 2.05-29.14, P<0.01) and perimyocarditis (IRR: 8.25; CI: 1.60-42.50, P = 0.01) within 30 days of ICI exposure. Subgroup analysis identified higher risks in patients aged ≥65, males, and those with diabetes, hypertension, or hyperlipidemia. Furthermore, when focusing on patients who received more than two doses of ICIs or exclusively anti-PD-1 inhibitors, we observed a similarly increased risk of HF within 30 days post-exposure. Collectively, ICI exposure significantly elevates the risk of heart failure and perimyocarditis within 30 days, particularly in older adults and those with preexisting cardiovascular risk factors.

Keywords: Immune checkpoint inhibitors; heart failure; perimyocarditis; self-controlled case series.

Figure 1

The flowchart of study design.

Figure 2

Subgroup analysis focusing on patients developing heart failure during 0-30 days post immune checkpoint inhibitors.

Figure 3

Using a nationwide self-controlled case series (SCCS) approach, among 1,146 ICI users the exposure of immune checkpoint inhibitors (ICIs) was associated with increasing incodences of cardiovascular complications within 30 days.