Beta-agonists linked to asthma deaths, says study

US researchers have called for three common asthma inhalers containing the drugs salmeterol or formoteral to be removed from the market.

  • E-Mail
By  Joanne Bladd Published  July 10, 2006

US researchers have called for three common asthma inhalers containing the drugs salmeterol or formoteral to be removed from the market, after a study suggested they cause four out of five US asthma-related deaths per year. The study, which analysed 19 published trials involving 33,826 patients, found that subjects who inhaled the long-acting beta-agonists salmeterol or formoterol were 3.5 times more likely to die from asthma and 2.5 times more likely to be hospitalised, compared to those taking a placebo. The reason, say the researchers, is because, although both drugs relieve asthma symptoms, they also promote bronchial inflammation and sensitivity without warning. Edwin Salpeter, the JG White Distinguished Professor of Physical Sciences Emiratus at Cornell, led the statistical analysis used in the study. “In total, there are about 5,000 deaths a year due to asthma, whether or not a person is taking a long-acting beta-agonist,” he said. “We can show that overall it is statistically significant that, compared to patients taking a placebo, these long-acting beta-agonists kill a lot of people.” His daughter, Dr Shelley Salpeter, is a clinical professor of medicine at Stanford. She was lead author on the study, which appeared in the 20 June 2006 issue of Annals of Internal Medicine. “These asthma deaths are generally in healthy young adults,” she said. “We estimate that approximately 4,000 out of the 5,000 asthma deaths that occur in the US each year are actually caused by these long-acting beta-agonists, and we urge that these agents be taken off the market.” Attempting to avoid the bronchial inflammation associated with beta-agonists by adding an anti-inflammatory drug offers little protection, the Salpeters reported. Adavir, for example, the fourth bestselling drug in the world, combines salmeterol with an anti-inflammatory drug. But hospitalisations still doubled for patients inhaling the drug combination, compared with asthma patients taking a placebo and an anti-inflammatory drug by itself. Of the 19 studies surveyed, the largest – the Salmeterol multicentre asthma research trial, with 26,000 participants – recorded a fourfold increased risk for asthma-related deaths, and a twofold increase in life-threatening asthma events, in patients using salmeterol. If older people who also suffered from chronic obstructive pulmonary disease were removed from the analysis, the Salpeters claim, salmeterol would be associated with a six times greater risk for asthma-related death. The analysis found that 53 of 3,083 patients inhaling beta-agonists were hospitalised for an asthma attack, compared with 12 of 2,009 patients who received a placebo. There was one hospitalisation for every 71 patients treated with a long-acting beta-agonist per year. The Salpeters believe use of salmeterol or formoterol can result in death, because patients develop tolerance to them over time. “These agents can improve symptoms through bronchiodilation at the same time as increasing underlying inflammation and bronchial hyper-responsiveness, thus worsening asthma control without any warning of increased symptoms,” said Shelley Salpeter. “It is particularly frightening that long-acting beta-agonists are detrimental, whether salmeterol or formoterol, whether taken alone or with anti-inflammatory drugs, both for children and adults,” Edwin Salpeter added.

Add a Comment

Your display name This field is mandatory

Your e-mail address This field is mandatory (Your e-mail address won't be published)

Security code