Key takeaways:

• Inflammation and corticosteroid use represent cardiovascular risks in asthma.
• Benralizumab and dupilumab presented less risk for stroke.
• Dupilumab presented the least risk for myocardial infarction.

PHOENIX — Adults with severe asthma who used biologics had lower risks for major adverse cardiovascular events than those on other therapies, according to an abstract presented at the CHEST Annual Meeting.

The chronic systemic inflammation associated with asthma as well as oral corticosteroid treatment both present increased risks for poor cardiovascular outcomes, Soham Nadkarni, MD, third-year resident, University of Tennessee Health Science Center, and colleagues wrote.

Data derived from Bagheri A, et al. Cardiovascular outcomes in patients with severe asthma treated with biologic therapy: A propensity score-matched analysis from the TriNetX network. Presented at: CHEST Annual Meeting; Oct. 18-21, 2026; Phoenix.

However, the researchers continued, the influence of biologics in asthma treatment on long-term cardiovascular outcomes remains unclear.

“These are patients who have been through years of oral steroid bursts before being referred to us and getting to a biologic, and many of them also have significant comorbidities including hypertension, obesity and diabetes,” Nadkarni told Healio.

“Severe asthma is known to increase cardiovascular morbidity,” he continued. “Biologics reduce exacerbations and spare steroids, and we wanted to see what adding a biologic does to that, and whether it translates into fewer hard cardiovascular events.”

In the clinic

The retrospective cohort study identified adults with severe asthma who were using biologics (n = 9,805) and matched them with adults with severe asthma who were not using biologics for treatment (n = 9,805), all from the TriNetX global health research network. In the pooled cohort, mean age was 53 years, 68% were women and 67% were white.

“Comorbidity burden was substantial: 29% had obesity, 43% had gastroesophageal reflux, 23% had hyperlipidemia and 8% with nicotine dependence,” Nadkarni said.

The treatment groups included 1,458 patients on benralizumab (Fasenra, AstraZeneca), 1,883 on dupilumab (Dupixent; Sanofi, Regeneron), 1,204 on mepolizumab (Nucala, GSK), 2,359 on omalizumab (Xolair; Genentech, Novartis) and 616 on tezepelumab (Tezspire; AstraZeneca, Amgen).

Patients were assessed for a 3-year composite major adverse cardiovascular event (MACE) including myocardial infarction, stroke, heart failure or all-cause mortality.

“Every outcome favored biologic therapy, and all reached significance,” Nadkarni said.

Hazard ratios included 0.74 (95% CI, 0.69-0.78) for composite MACE, 0.64 (95% CI, 0.52-0.79) for myocardial infarction, 0.64 (95% CI, 0.51-0.79) for stroke, 0.56 (95% CI, 0.5-0.62) for heart failure and 0.5 (95% CI, 0.41-0.62) for all-cause mortality.

Specifically, percentages of patients with MACE included 18.4% of the benralizumab group and 27.8% of the control group (HR = 0.61; 95% CI, 0.52-0.71), 17.5% of the dupilumab group and 24.9% of the control group (HR = 0.73; 95% CI, 0.63-0.84), 20.9% of the mepolizumab group and 24.8% of the control group (HR = 0.79; 95% CI, 0.67-0.94) and 20.3% of the omalizumab group and 22.7% of the control group (HR = 0.82; 95% CI, 0.72-0.93).

Although there was a similar reduction in MACE among patients with tezepelumab, the researchers said, it was not statistically significant. Yet Nadkarni said these findings deserve a closer look.

“Composite MACE did not reach significance [with tezepelumab], but heart failure did, at 0.43 (95% CI, 0.27-0.69),” he said. “That is the smallest cohort and the most recently approved agent, so follow-up is shortest and several outcomes had fewer than 10 events and were suppressed by the network.”

Risks for heart failure fell by 50% with benralizumab and 35% with dupilumab (both, P < .001). Risks for stroke were significantly lower with benralizumab and dupilumab as well, the researchers added.

Dupilumab further offered significantly lower risks for myocardial infarction, the researchers continued, whereas patients on other biologics had directionally favorable outcomes too. Finally, benralizumab and dupilumab had particularly notable reductions in all-cause mortality, with reductions among the other groups as well.

“And for transparency, one estimate went the other way,” Nadkarni said. “All-cause mortality with omalizumab was not statistically significant, and the only point estimate above 1 among more than 40 comparisons. I don’t think it should be over-interpreted in either direction, but it should be reported.”

Next steps

Based on these findings, the researchers said that biologic therapies reduce risks for adverse cardiovascular outcomes among patients with severe asthma.

Nadkarni said that the consistency of these findings make them significant as results from all five biologics pointed in the same direction with 3-year MACE lower for each drug.

“What stands out is that these drugs hit different targets — IL-5 and IL-5R, IL-4 and IL-13, IgE, [thymic stromal lymphopoietin] — so it is hard to explain this through any one pathway,” Nadkarni said. “It points instead to something the drugs share, like fewer exacerbations and less steroid exposure.”

The results for heart failure also were significant, he continued, as it was the only outcome with lower results among all of the biologic treatment groups.

“One in 10 control patients developed heart failure within 3 years,” Nadkarni said. “That matters because heart failure is the cardiovascular problem that asthma raises the most.”

Nadkarni cautioned, however, that these findings are associations in propensity-matched observational data and that they do not account for eosinophil counts, doses with steroids, history of exacerbations, or lung function.

“And patients who get a biologic may be healthier in ways we could not measure, since getting one means being referred, approved, and then coming in regularly for years,” he said. “These findings are hypothesis-generating.”

Nadkarni advised clinicians to treat severe asthma as a systemic inflammatory condition with comorbid cardiovascular risks, with an eye on controlling blood pressure and lipid and glucose levels in addition to pulmonary considerations.

“It also means asking specifically about heart failure symptoms early, because exertional dyspnea in a severe asthma patient is easy to attribute to the asthma,” he said.

Noting that biologic therapy already strives to spare patients steroid use, Nadkarni also said these findings provide additional reason to minimize and track oral corticosteroid dosages.

“For a patient with severe asthma who also has cardiovascular comorbidity, this is at least reassuring that starting a biologic is not adding cardiovascular risk,” he said.

However, he also cautioned that clinicians should not prescribe biologics for cardiovascular protection, which the data do not support.

“When we judge how well a biologic works, we have mainly considered the respiratory effects — exacerbations, lung function, steroid use,” he said.

“Our study adds another dimension to that,” he added. “Cardiovascular endpoints deserve a place in how we evaluate biologic therapy in severe asthma. The next studies should adjust for eosinophil count and steroid burden, and follow patients longer.”

For more information:

Soham Nadkarni, MD, can be reached at snadkarni@utmck.edu.