Beta-1 blocker use linked to higher mortality in immune checkpoint inhibitor patients

Patients with cancer who were already taking beta-1 selective beta-blockers when they began immune checkpoint inhibitor therapy showed significantly higher all-cause mortality than patients not on these drugs, according to a retrospective single-center study published in Supportive Care in Cancer. Among 2,409 patients treated with immune checkpoint inhibitors, 591 patients, or 25 percent, were pretreated with beta-1 selective beta-blockers. Mortality in that group reached 68 percent, compared with 57 percent among patients not taking the medication, a difference that remained statistically significant after adjustment for other factors.

The findings are notable because they run counter to earlier signals from studies of non-selective beta-blockers, which have been associated with improved efficacy of immune checkpoint inhibitor therapy. Beta-adrenergic signaling has been implicated in cancer initiation and progression, and the research team set out to determine whether beta-1 selective blockade, the class most commonly prescribed for cardiovascular conditions, was associated with survival or with cardiovascular immune-related adverse events in patients receiving checkpoint inhibitors. The answer for mortality was yes, and for cardiovascular events it was not.

The two groups differed substantially at baseline, which shapes how the results should be read. Patients on beta-1 blockers were older on average, at 72 plus or minus 9 years versus 64 plus or minus 13 years, and carried a far heavier burden of cardiac disease. Ischemic heart disease was present in 40 percent of the beta-blocker group versus 8 percent of the comparison group, heart failure in 9 percent versus 2 percent, and atrial fibrillation in 15 percent versus 3 percent, all differences reaching statistical significance. These imbalances reflect the clinical reality that beta-blockers are prescribed for cardiovascular indications, and they raise the possibility of confounding by indication, meaning the drug may simply mark a sicker population rather than cause worse outcomes.

To address that concern, the investigators performed a multivariate analysis. Baseline beta-1 selective beta-blocker therapy remained a strong independent predictor of all-cause mortality, with a hazard ratio of 1.21 and a 95 percent confidence interval of 1.05 to 1.39, corresponding to a p value of 0.010. In other words, even after accounting for measured differences between the groups, the association persisted. Importantly, the researchers report that the association between baseline beta-1 blocker treatment and increased mortality was consistent among patients both with and without baseline cardiovascular disease, suggesting the signal was not confined to those with pre-existing heart conditions.

Cardiovascular immune-related adverse events told a different story. Unadjusted rates were higher in the beta-blocker group, at 14 percent versus 7 percent, driven mainly by heart failure, which occurred in 7 percent versus 3 percent, and atrial fibrillation, which occurred in 7 percent versus 3 percent. Yet once the analysis adjusted for other variables, beta-1 blocker use was no longer a significant predictor of these cardiovascular events, with a hazard ratio of 1.22, a 95 percent confidence interval of 0.84 to 1.77, and a p value of 0.290. The study therefore does not establish beta-1 blocker use as an independent predictor of cardiovascular immune-related adverse events in this population.

Immune checkpoint inhibitors have transformed cancer care by releasing immune cells to attack tumors, but that immune activation can also inflame healthy organs, including the heart. The higher unadjusted rates of heart failure and atrial fibrillation among beta-blocker users in this cohort likely reflect their greater baseline cardiac vulnerability rather than a drug effect, given that the adjusted analysis did not support an independent association.

As an observational, retrospective study conducted at a single center, the analysis cannot establish causation, and unmeasured differences between the groups may still contribute to the mortality gap. The authors conclude that baseline beta-1 selective beta-blocker therapy may be an independent predictor of increased all-cause mortality in patients treated with immune checkpoint inhibitors, a phrasing that appropriately signals an association requiring further study rather than a proven causal effect.

The results underscore that prior beta-blocker exposure is a measurable characteristic associated with outcomes in this setting, while leaving open the question of whether the drug, the underlying cardiovascular disease it treats, or both contribute to the observed association. Larger prospective studies would be needed to determine whether beta-1 selective blockade itself influences survival in patients receiving checkpoint inhibitor therapy, and whether the mortality signal seen here distinguishes this class from non-selective beta-blockers in the same population.

Subject of Research: Association of baseline beta-1 selective beta-blocker use with all-cause mortality and cardiovascular immune-related adverse events in patients treated with immune checkpoint inhibitors

Article Title: Prognostic role of selective beta-1 blockers in patients treated with immune checkpoint inhibitors

Article References: Perelman, M. G., Brzezinski, R. Y., Gefen, S., Merin, R., Miodovnik, M., Raphael, A., Wolf, I., Hemed, A. R., Perelman, M., Slieman, M., Khoury, S., Havakuk, O., Topilsky, Y., Banai, S., Leshem, Y., & Laufer-Perl, M. (2026). Prognostic role of selective beta-1 blockers in patients treated with immune checkpoint inhibitors. Supportive Care in Cancer, 34(11), Article 1156. https://doi.org/10.1007/s00520-026-11366-7

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11366-7

Keywords: immune checkpoint inhibitors, beta-1 blockers, all-cause mortality, cardiovascular immune-related adverse events, heart failure, atrial fibrillation, ischemic heart disease, retrospective study, oncology, cardio-oncology, cancer immunotherapy, prognosis