Key result
PD-1 inhibitors linked to ~111% higher incident heart failure risk in patients with prior ischemic events.
Why the study?
Immune checkpoint inhibitors often cause cardiovascular adverse effects, prompting investigation into whether prior cardiac ischemic injury exacerbates anti-PD-1-related cardiac dysfunction and whether abatacept ameliorates this cardiotoxicity.
Does pre-existing ischemic heart disease increase the risk of incident heart failure in cancer patients receiving PD-1 inhibitors?
Does pre-existing ischemic heart disease increase the risk of incident heart failure in cancer patients receiving PD-1 inhibitors?
Prior ischemic heart disease is associated with a doubled risk of incident heart failure in cancer patients treated with PD-1 inhibitors, a cardiotoxic effect that may be ameliorated by abatacept co-treatment.
Prior ischemic events may double the risk of incident heart failure during PD-1 inhibition; leaves open whether.
Aims Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment. However, their use often leads to cardiovascular adverse effects, including cardiac dysfunction. Here, we hypothesized that a prior cardiac ischemic injury could exacerbate cardiac dysfunction due to anti-PD-1 treatment. Furthermore, we investigated whether abatacept, a T-cell co-stimulation blocker, could ameliorate the ICI-induced cardiotoxicity in a preclinical model. Methods and results In a preclinical study, mice were treated with isoprenaline or control to induce reversible cardiac ischemia. After 16 weeks of follow-up, recovery of cardiac function was confirmed via echocardiography, and mice from both groups were randomly treated with isotype control, anti-PD-1, or anti-PD-1 combined with abatacept, for two further weeks. Mice with prior ischemic injury and anti-PD-1 treatment showed cardiac dysfunction with increased infiltration of T-cells and macrophages and elevated expression of pro-inflammatory cytokines. Conversely, cardiac dysfunction and inflammation were less pronounced after anti-PD-1 treatment in mice without prior ischemic injury. Mice with concomitant abatacept treatment exhibited normal cardiac function and alleviated pro-inflammatory response. In a parallel single-center retrospective clinical cohort study, 1,671 cancer patients receiving PD-1 inhibitors were analyzed. Cases were defined as patients who developed incident HF after ICI initiation with a primary aim to test whether pre-existing ischemic heart disease was associated with an increased risk for HF development post-ICI therapy. Sensitivity analyses included propensity score matching and comparison with non-ICI-treated cancer patients. Among ICI-treated patients, 109 (6.5%) developed HF over a median follow-up of 332 days. Multivariable logistic regression of the matched population showed increased odds of incident HF in patients with prior ischemic cardiac events (OR 2.11 95%, CI 1.05-4.2, p=0.033). Conclusion In mice, induction of cardiac inflammation and dysfunction by anti-PD1 therapy was potentiated by prior transient ischemic cardiac injury, which was ameliorated by abatacept co-treatment. Cancer patients with pre-existing ischemic heart disease may be at greater risk for developing ICI-induced new-onset HF. Based on our findings, cardiac surveillance should be considered in patients starting ICI therapy with a prior history of ischemic heart disease.
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Gergely et al. (2026) studied this question. Cancer patients with prior ischemic cardiac events treated with PD-1 inhibitors had significantly increased odds of developing incident heart failure (OR 2.11, 95% CI 1.05-4.2).
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