Four in five asthma deaths may be due to long acting β agonists

Eighty per cent of deaths related to asthma in the United States may be due to the use of long acting β agonists, indicate the results of a meta-analysis of 19 clinical trials.

The results of the review, published in the Annals of Internal Medicine (2006;144; 901-12), have led to calls for the drugs to be withdrawn from the US market.

“We can show that overall it is statistically significant that, compared with patients taking a placebo, these long acting β agonists kill a lot of people,” said the lead researcher, Edwin Salpeter from Cornell University.

The analysis concludes that 4000 of the 5000 asthma related deaths in the US each year occur in patients who are taking the drugs. Although they can relieve the symptoms of asthma they can also, without warning, trigger bronchial inflammation and sensitivity.

Long acting β agonists, such as salmeterol, made by GlaxoSmithKline, and formoterol, made by Novartis, first emerged in the early 1990s. They are designed to be used for asthma that is not fully controlled by inhaled steroids and bronchodilators.

Taken alongside those drugs they can relieve symptoms after 15 to 20 minutes, and their effects can last for up to 12 hours. They work by relaxing muscles in the airways so that more air can get into the lungs.

But their use has been dogged by fears about safety. The US Food and Drug Administration raised concerns last year after some post-marketing safety studies indicated a possible increased risk of serious adverse events.

The latest evidence comes from studies involving almost 34 000 patients in 19 trials around the world.

The pooled data indicate that patients taking long acting β agonists are 3.5 times more likely to die from asthma and 2.5 times more likely to be hospitalised than those taking a placebo.

The researchers stressed, however, that deaths from asthma were still relatively rare.

The controversial findings raise important questions about the treatment of asthma.

Martyn Partridge, chief medical adviser for the charity Asthma UK, said, “This is a situation where we must ‘watch this space.' Reports of adverse effects are not new, and there was a statistically non-significant excess of deaths in patients on salmeterol in the original post-marketing surveillance study.

“For me the bottom line is [that] for those with more than very occasional asthma give low dose inhaled steroids. Only add a LABA [long acting β agonist] if asthma is not well controlled, and don't continue it if it does not benefit the patient.”