• Researchers observed heightened risks for heart failure, arrhythmia and mortality with short-acting muscarinic antagonist (SAMA) use in patients with asthma and COPD.
• This was also true with SABA plus SAMA use.

Patients with asthma and COPD using at least three short-acting bronchodilators canisters a year vs. none had an elevated risk for cardiovascular events and all-cause mortality, according to data published in ERJ Open Research.

“For the everyday clinician, these findings show the importance of closely monitoring the overuse of short-acting bronchodilators in both asthma and COPD patients and assessing cardiovascular risk,” Lies Lahousse, PharmD, PhD, associate professor at Ghent University, told Healio. “Given it is a marker of poor disease control, it also requires reassessing adherence and inhaler technique of maintenance treatment.”

Using 2017 to 2022 data from a Belgian nationwide cohort, Lahousse and colleagues evaluated 226,314 adults with asthma (mean age, 57.8 years; 60.5% women) and 57,446 adults with COPD (mean age, 72.2 years; 38% women) to determine the impact of SABA, short-acting muscarinic antagonist (SAMA) and SABA plus SAMA use on the risk for adverse cardiovascular outcomes and all-cause mortality.

“From our nationwide research among 1 million adult chronic users of drugs for obstructive airway diseases published in 2025 in ERJ Open Research, heavy overuse of short-acting bronchodilators (defined as ≥ 6 packages per year) turned out to be one of the most significant predictors for mortality and hospitalized exacerbations,” Lahousse told Healio.

“Therefore, we wondered whether this signal was associated with cardiac side effects, whether it was driven primarily by SABA or SAMA overuse, or the combination, and which patients would be most vulnerable,” she said.

Among those with asthma, 53.8% did not use any short-acting bronchodilator canisters during the baseline year, 29.2% used one to two and 17% used at least three (overuse). When broken down by bronchodilator type, 23.8% used SABA canisters (16.8% one to two; 7% at least three), 4.5% used SAMA canisters (3.8% one to two; 0.7% at least three) and 22.4% used SABA plus SAMA canisters (13.8% one to two; 8.6% at least three).

In the group with COPD, 38% did not use any short-acting bronchodilator canisters in the baseline year, 32.3% used one to two and 29.6% used at least three. Broken down by type, 11.5% used SABA canisters (7.3% one to two; 4.2% at least three), 7% used SAMA canisters (5.4% one to two; 1.6% at least three) and 51.7% used SABA plus SAMA canisters (28.3% one to two; 23.4% at least three).

Following adjustment for age, sex, smoking, socioeconomic status, exacerbation history, comorbidities and medication use, researchers found that patients with asthma using vs. not using SAMA had a significantly elevated risk for:

• heart failure (1-2: adjusted HR = 1.32; 95% CI, 1.25-1.39; ≥ 3: aHR = 1.35; 95% CI, 1.21-1.51);
• arrhythmia (1-2: aHR = 1.18; 95% CI, 1.13-1.24; ≥ 3: aHR = 1.27; 95% CI, 1.15-1.4);
• all-cause mortality (1-2: aHR = 1.33; 95% CI, 1.28-1.38; ≥ 3: aHR =1.73; 95% CI, 1.6-1.87);
• myocardial infarction (≥ 3: aHR = 1.43; 95% CI, 1.09-1.87); and
• angina (≥ 3: aHR = 1.6; 95% CI, 1.03-2.51).

The study reported comparable findings for SABA plus SAMA use, as patients with asthma with vs. without use of this combination had a significantly heightened risk for:

• heart failure (1-2: aHR = 1.23; 95% CI, 1.18-1.27; ≥ 3: aHR =1.44; 95% CI, 1.38-1.5);
• arrhythmia (1-2: aHR = 1.12; 95% CI, 1.08-1.15; ≥ 3: aHR =1.21; 95% CI, 1.17-1.26);
• all-cause mortality (1-2: aHR = 1.28; 95% CI, 1.25-1.32; ≥ 3: aHR =1.7; 95% CI, 1.64-1.76);
• myocardial infarction (1-2: aHR = 1.15; 95% CI, 1.05-1.26; ≥ 3: aHR =1.46; 95% CI, 1.31-1.62);
• angina (1-2: aHR = 1.19; 95% CI, 1.02-1.39); and
• ischemic stroke (1-2: aHR = 1.15; 95% CI, 1.04-1.28; ≥ 3: aHR =1.31; 95% CI, 1.15-1.48).

Similar to the group with asthma, patients with COPD using vs. not using SAMA had significantly elevated risks for heart failure (1-2: aHR = 1.2; 95% CI, 1.12-1.28; ≥ 3: aHR =1.33; 95% CI, 1.18-1.49), arrhythmia (1-2: aHR = 1.23; 95% CI, 1.16-1.31; ≥ 3: aHR =1.41; 95% CI, 1.27-1.57), all-cause mortality (1-2: aHR = 1.23; 95% CI, 1.17-1.29; ≥ 3: aHR =1.36; 95% CI, 1.25-1.49) and angina (≥ 3: aHR = 1.77; 95% CI, 1.1-2.83).

With use of SABA plus SAMA vs. no combination use, researchers observed significantly raised risks for heart failure (1-2: aHR = 1.11; 95% CI, 1.07-1.15; ≥ 3: aHR =1.27; 95% CI, 1.22-1.32), all-cause mortality (1-2: aHR = 1.1; 95% CI, 1.07-1.14; ≥ 3: aHR =1.4; 95% CI, 1.35-1.44), arrhythmia (≥ 3: aHR =1.16; 95% CI, 1.11-1.2) and myocardial infarction (≥ 3: aHR = 1.35; 95% CI, 1.22-1.51).

In the subgroup of patients with asthma without prior cardiovascular disease, the study found a significantly increased risk for a compositive CV outcome with SAMA use (1-2 canisters/year and ≥ 3 canisters/year) and SABA plus SAMA use (1-2 and ≥ 3) and for all-cause mortality with SABA use (≥ 3), SAMA use (1-2 and ≥ 3) and SABA plus SAMA use (1-2 and ≥ 3).

The same pattern for these risks was noted in patients with COPD without prior cardiovascular disease.

“The higher risk of cardiovascular outcomes and all-cause mortality by increasing SAMA (combination) canisters was remarkable,” Lahousse said. “We observed these associations both in patients with asthma and COPD, and surprisingly also in those not already known with cardiovascular disease.”

When evaluating SABA use, patients with asthma using at least three SABA canisters/year vs. none had a significantly greater risk for heart failure (aHR = 1.08; 95% CI, 1.01-1.15), myocardial infarction (aHR = 1.16; 95% CI, 1-1.34) and mortality (aHR = 1.12; 95% CI, 1.06-1.18). In patients with COPD, this was also true for the risk for heart failure (aHR = 1.13; 95% CI, 1.04-1.22) and mortality (aHR = 1.14; 95% CI, 1.08-1.22).

Use of one to two SABA canisters/year vs. none was not linked to elevated risks for mortality or adverse cardiovascular outcomes in either group, according to the study.

In both groups, researchers found that patients using one to two SABA canisters/year vs. none had a significantly reduced risk for all-cause mortality (asthma: aHR = 0.85; 95% CI, 0.81-0.89; COPD: aHR = 0.92; 95% CI, 0.88-0.97). In the asthma group, patients with this type of use also had a significantly reduced risk for arrythmia (aHR = 0.95; 95% CI, 0.91-0.99).

“Our results support better surveillance of short-acting bronchodilator overuse, also in primary care, and novel strategies to address multimorbidity and achieve better disease control,” Lahousse told Healio.

Lies Lahousse, PharmD, PhD, can be reached via Frauke Van Vaerenbergh, PharmD, at frauke.vanvaerenbergh@ugent.be.