The beta-blocker shows no respiratory harm, but not much cardiovascular benefit either.
Bisoprolol can be safely prescribed to patients with moderately severe chronic obstructive pulmonary disease, researchers have concluded.
The findings from the Australian-led multinational PACE trial have eased long-standing concerns that beta-blockers worsen respiratory outcomes in this population, showing no increase in exacerbations, lung function decline, hospitalisations or deaths with bisoprolol compared with placebo over two years.
According to the researchers, the findings also indicated that beta blockers had no benefit for primary prevention of cardiac or respiratory events in patients with COPD without cardiovascular indications.
“However, the absence of an elevated risk of adverse events shows that that highly selective β1 blockers are well tolerated in patients with COPD if there is a clear indication for a β blocker,” they wrote.
“Although the high risk of cardiovascular disease in patients with COPD is well established from observational studies, particularly in the setting of an acute exacerbation, the low rate of major cardiovascular events in this and previous randomised controlled trials of β blockers suggests that the absolute risk of these events should be re-evaluated.”
Results have been published in The Lancet Respiratory Medicine.
COPD is Australia’s leading cause of preventable hospital admissions, with patients dying from cardiovascular disease (CVD) almost as often as from their lung disease.
However, treating their CVD has been a challenge given the long-standing view that beta blockers were contraindicated, despite many large databases suggesting this drug class had mortality and exacerbation rate benefits for people with COPD.
The double-blind, randomised, placebo-controlled phase 3 study enrolled 280 patients aged 40–85 years with COPD at 22 hospital and research sites in Australia, India, New Zealand and Sri Lanka.
Participants were randomised to bisoprolol (143) or placebo (137), with 249 completing two years of follow-up. Participants were mostly male (83%), with a mean age of 68 years, and had moderate–severe airflow limitation (mean FEV₁ 45% predicted).
Bisoprolol did not improve overall cardiorespiratory outcomes compared with placebo (win ratio 0.95; 95% CI 0.72–1.25; p=0.72), showing a small, non-significant net disadvantage (–2%).
There were no significant differences between groups in all-cause mortality, cardiorespiratory hospitalisations, major cardiac events, COPD exacerbations, lung function, symptoms, quality of life or adverse events.
COPD exacerbations were the most common adverse event in both groups. Deaths occurred in 10% of the bisoprolol group and 8% of the placebo group, with none attributed to treatment.
Lead investigator Professor Christine Jenkins from The George Institute for Global Health, told The Medical Republic the findings added weight to a recent randomised control trial conducted in the UK and published in JAMA that also found no association between bisoprolol and increased respiratory adverse reactions or other adverse reactions compared to placebo in patients with COPD.
She said another important outcome of this study and the UK study was the importance of earlier diagnosis of COPD, and assessment of these patients for their cardiac risks.
“We don’t know categorically that cardiovascular medicines have the same effect for COPD patients as they do for the broad cardiovascular population,” said Professor Jenkins.
Related
“Three good studies have shown no benefit with beta blockers. The BLOCK COPD [Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease study] was published in the New England Journal, the UK study was published in JAMA, and our study published in The Lancet, and they they’ve gone under very high-level peer review.
“We have concerns that COPD patients may respond differently to cardiovascular interventions than a patient with a pure cardiovascular indication, and that might be because the lung disease that’s driving that cardiac manifestations is strongly embedded in the patient.”
Different respiratory mechanics in COPD patients may also play a key role, she said.
“They tend to have a very rapid respiratory rate, which reduces their filling time in their hearts,” she said.
“There’s a whole lot of reasons why they may be less beneficially affected by cardiovascular interventions, medical interventions and pharmacotherapy.
“So, we really still have some unanswered questions about how best to manage cardiovascular disease in COPD.”
Professor Jenkins said it appeared that major cardiovascular events such as myocardial infarction, heart failure and arrhythmia were actually more common amongst patients with moderate COPD than severe COPD.
“There’s a sense in which you could say the severe COPD patients are the survivors and it’s in the moderate COPD patients where those cardiovascular risks are most prominent, and so earlier recognition of the fact that the patient has COPD and may have comorbid cardiac disease is a really important red flag for GPs,” she told TMR.
“Also, the opportunity in moderate COPD to take preventative steps is really substantial, like stopping smoking, promoting exercise, reducing weight, controlling diabetes if it’s present and managing the COPD optimally.
“If you can do all those things in a preventative intervention in patients with moderate COPD, you may well be changing the course of their life expectancy and likely cardiac events.
“Reducing their exacerbation rate by managing their COPD and helping them to avoid infections, be vaccinated, etc, can reduce their cardiac risks as well.”
