Beta-blocker bisoprolol fails to lower COPD exacerbations in patients at high risk
Click Here to Manage Email Alerts
Key takeaways:
- Bisoprolol use in COPD was deemed “not clinically beneficial” by researchers.
- In both the bisoprolol group and the placebo group, around 14% of patients experienced serious adverse events.
SAN DIEGO — Bisoprolol treatment yielded a similar yearly rate of COPD exacerbations that require oral corticosteroids and/or antibiotics to placebo, according to research presented at the American Thoracic Society International Conference.
“For frequently exacerbating [Global Initiative for Chronic Obstructive Lung Disease] E COPD type patients, taking bisoprolol compared to placebo did not reduce exacerbations, and notably, we didn’t see any safety concerns for serious adverse events either,” Brian J. Lipworth, MD, head of the Scottish Centre for Respiratory Research and professor of allergy and pulmonology at University of Dundee, said during his presentation.
In a double-blind, placebo-controlled, randomized clinical trial (Bisoprolol in COPD Study), Lipworth and colleagues assessed 515 adults (mean age, 68 years; 53% men; mean FEV1, 50.1%; 31% current smokers) with COPD at high risk for exacerbation in the U.K. to determine the impact of a daily oral dose of bisoprolol on the incidence of treated COPD exacerbations in 1 year vs. placebo.
Included patients met two disease characteristics: at least moderate airflow obstruction (FEV1/FVC < 0.7; FEV1 < 80% predicted) and a minimum of two treated (oral corticosteroids, antibiotics or both) COPD exacerbations in the past year.
After randomization, the bisoprolol group included 259 patients (mean age, 67.7 years; 51.7% men; mean FEV1, 49.2% predicted; 30.1% current smokers) with a starting dose of 1.25 mg per day, and the placebo group included 256 patients (mean age, 67.7 years; 54.7% men; mean FEV1, 51.1% predicted; 32% current smokers).
Both groups had comparable patient proportions across a range of COPD therapies, including triple combination therapy with an inhaled corticosteroid, long-acting beta-agonist and long-acting muscarinic antagonist (bisoprolol, 74.1%; placebo, 73.4%).
Within four sessions, researchers said the bisoprolol dose was titrated as tolerated. The highest dose patients could receive was 5 mg per day.
The most common fixed doses of daily bisoprolol included 5 mg (27%) and 1.25 mg (24%), followed by 2.5 mg (16%) and 3.75 mg (14%).
All but one patient (placebo group) had data on the number of treated COPD exacerbations in the 1-year time span.
Between the bisoprolol group and the placebo group, researchers observed a similar total number of COPD exacerbations treated with oral corticosteroids and/or antibiotics (526 vs. 513) and a similar yearly exacerbation rate (mean, 2.03 per year vs. 2.01 per year).
Following adjustment for several variables (study center, primary or secondary care recruitment, age centered on the mean, sex, smoking status, FEV1 of expiration percentage), the incidence rate ratio did not significantly differ between the two treatments.
Patients receiving bisoprolol also did not significantly differ from patients receiving placebo in terms of median time to first COPD exacerbation following randomization, COPD exacerbation hospitalizations, non-COPD-related hospitalizations, all-cause mortality risk and COPD Assessment Test scores.
Researchers did note significant differences when comparing the bisoprolol group vs. the placebo group during evaluation of COPD-related mortality risk (HR = 0.19; 95% CI, 0.04-0.88; P = .03) and Transition Dyspnea Index score-quantified dyspnea at 52 weeks (mean difference, –0.73; 95% CI, –1.44 to –0.01; P = .05).
“[For the COPD-related mortality finding], the numbers are small: two in the bisoprolol group and 10 in the placebo group,” Lipworth said. “Personally, I wouldn’t really read too much into that impact on COPD mortality.”
Lipworth added that he “really wouldn’t put too much emphasis” on the change in Transition Dyspnea Index either since it was less than the minimum clinically important difference value.
After factoring out those who did not begin their assigned treatment (bisoprolol and placebo each, n = 4), those with adherence less than 70% (bisoprolol, n =8; placebo, n = 6) and discontinuations (bisoprolol, n = 73; placebo, n = 62), only 174 patients remained in the bisoprolol group, and 183 patients remained in the placebo group.
In this filtered population, researchers again found that bisoprolol did not significantly differ from placebo with regard to the adjusted incidence rate ratio for treated COPD exacerbations and for hospitalization-required COPD exacerbations.
In terms of safety, 14.5% of patients receiving bisoprolol experienced serious adverse events, and this was nearly identical to the proportion found in the placebo group (14.3%).
Slightly more patients receiving placebo vs. bisoprolol had respiratory serious adverse events (11 vs. 4) and respiratory adverse reactions (12.3% vs. 9.8%).
When discussing limitations, Lipworth highlighted the COVID-19 pandemic.
“This study was affected by the COVID pandemic, and we ended up enrolling only 500 of the 1,500 planned patients, and that obviously does have an impact in terms of potential statistical power,” he said during his presentation.