Drug use and pulmonary death rates in increasingly symptomatic asthma patients in the UK

There is concern about an increase in deaths from respiratory causes in asthma patients using long acting beta agonists. According to the guidelines of the British Thoracic Society, long acting beta agonists, ipratropium bromide, and theophylline should be used to treat patients with increasing asthma severity who are already receiving treatment with short acting beta agonists and inhaled steroids. A study was therefore undertaken to compare the characteristics and short term respiratory mortality rates in first time users of one of these three drugs.

An open cohort study with a nested case-control analysis was performed on the UK based General Practice Research Database (GPRD). First time users of either salmeterol (n = 8386), ipratropium bromide (n = 4305), or theophylline (n = 4228) between 1 January 1992 and 30 April 1995 were identified and followed for 16 weeks. Drug usage patterns, predictors for respiratory mortality, and the number of deaths at 16 weeks in the three drug groups were compared.

The three asthma drugs were most often prescribed to patients with severe asthma. Age, a concomitant diagnosis of chronic obstructive pulmonary disease or emphysema, number of asthma drug prescriptions, number of visits to the general practitioner, and whether or not the patient had been admitted to hospital due to the respiratory disease in the 12 months prior to the start of the new drug therapy were strong predictors for asthma mortality. After adjusting for several risk factors, the relative risk estimates of a respiratory death for ipratropium bromide and theophylline users compared with salmeterol users were 1.8 (95% CI 0.4 to 9.6) and 3.0 (95% CI 0.4 to 22.4), respectively.

In the UK population studied, salmeterol, ipratropium bromide and theophylline are regularly used to treat patients with asthma of increasing severity. Salmeterol use was not associated with an increase in short term mortality compared with ipratropium bromide and theophylline.