Topical beta-blockers cause respiratory obstruction for one in every 55 patients

Ana Hidalgo-Simón MD, PhD
in London

ONE patient in every 55 treated with topical beta-blockers for glaucoma or ocular hypertension develops a respiratory obstruction which requires medical intervention, a large epidemiological study has found.

Almost half a million elderly people suffer from glaucoma in the UK. The majority of these are treated with a topical beta-blocker. Although it is well known that beta-blockers can exacerbate bronchospasm in predisposed patients — such as sufferers from asthma or chronic obstructive pulmonary disease — the topical treatment is assumed to be safe for non-risk patients.

Until now, that is. A team of researchers led by James F Kirwan MD at the Institute of Ophthalmology in London, looked into the effects of topical beta-blockers in elderly patients without obvious risk factors for pulmonary disease.
Dr Kirwan and his colleagues searched the Mediplus database for elderly patients with no previous diagnosis of airways obstruction who had used ophthalmic topical beta-blockers for the first time in the period 1993 to 1997. They identified 2,645 patients and more than 9,000 unexposed subjects.

The average age of selected patients was 68.6 years, slightly older than controls who averaged 67.5. Those in the selected group were also less likely to smoke and slightly more likely to visit their GP.

The researchers used two different sets of criteria for respiratory disease evaluation.
Low-level disease status was given to those patients who in the 12 months after treatment with topical beta-blockers first received a drug used for the treatment of reversible airways obstruction (2 agonists, inhaled corticosteroids, theophyllines and inhaled anticholinergics).

High-level disease status was given to patients who, in addition to the low level situation, recorded a diagnosis of asthma or chronic obstructive pulmonary disease.
The investigators found that 3,358 patients had been prescribed beta-blockers — and that includes a substantial number of patients who had a previous episode of airway obstruction. Of these, 148 (4.4%) had used drugs for airways obstruction within the previous year. Airways obstruction had been identified as an active problem (high level of disease definition) within the previous year in 316 subjects (9.4%).

Using the low level of disease definition, the authors found an adjusted hazard ratio at 12 months after treatment with topical beta-blockers of 2.29 (95% confidence interval 1.71 to 3.07), equivalent to a number needed to harm of 55 patients.

"Our study depends on a diagnosis of airways obstruction having been made. Allowing for a certain rate of missed diagnosis or misdiagnosis, we may have underestimated the true risk", Dr Kirwan said.

He added that patients with pre-existing airways obstruction may well be more sensitive to beta-blockers.
Under-diagnosis of respiratory conditions may be aggravated by a lower awareness of bronchospasm in elderly as opposed to younger patients, and by reduced mobility caused by arthritis and other conditions which prevent exercise and, therefore, breathlessness.

These results draw attention to the controversy of treating rather than not treating patients with glaucoma or ocular hypertension who are unlikely to benefit from treatment during their lifetimes.

“Many frail elderly patients may be better off left untreated rather than risk airway obstruction because their eyesight will not be affected,” Dr Kirwan said.
He explained that this assessment applies especially to very elderly patients with several associated conditions, in whom ocular hypertension or early stage glaucoma will not have time to develop into a disease-threatening blindness.

The investigators suggested that beta-blockers should be discontinued by the GP or clinician in charge of the patient as soon as a patient develops airways obstruction, and their ophthalmologist informed.

“These drugs can potentially kill people. When an airway obstruction develops they should be withdrawn. Their vision would not be severely affected by a month or two delay until they see their ophthalmologists,” he stressed.
A repeat prescription which includes topical beta-blockers and drugs for asthma should automatically sound an alarm for pharmacists, GPs and ophthalmologists.

“Measuring patient spirometry in ophthalmology outpatient clinics is easy to perform and it should be possible to routinely undertake the test when elderly patients are prescribed topical beta-blockers. Peak flow measurement can be a good surrogate marker for lung function,”Dr Kirwan suggested.

Despite their well known detrimental effects on respiratory function, beta-blockers are widely seen as beneficial in the treatment and prevention of other conditions. The use of beta-blockers in patients with heart failure has been shown to improve overall mortality considerably.

A recently published study by Yoshikawa et al (Cardiology 2003; 99: 47-53) found that early use of beta-blockers was associated with attenuation of serum C-reactive protein elevation and favourable short-term prognosis after acute myocardial infarction.
The results of Dr Kirwan’s study were published in the British Medical Journal in December 2002.

James F Kirwan
Institute of Ophthalmology, London, UK
Email: jfkirwan@ucl.ac.uk

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