By Christian Duffin
COPD patients taking the long-acting antimuscarinic tiotropium are 30% less likely to be hospitalised compared with those taking long-acting beta agonists, say researchers.
The results of the first long-term head-to-head study of the two treatments, found tiotropium prolonged the time to a first exacerbation and reduced the risk of hospitalisation because of a severe exacerbation in patients with COPD, compared with salmeterol.
One of the study’s GP investigators said the results represent a challenge to current NICE guidelines for maintenance therapy, which do not distinguish between long-acting antimuscarinic antagonists such as tiotropium, or long-acting beta agonists such as salmeterol as first-line therapy.
The 12-month randomised controlled trial, by an international group of researchers, involved 7,376 patients in 25 countries with moderate to very severe disease, who were randomised to long-acting bronchodilator treatment with either 18 ?g of tiotropium once a day or 50 ?g of salmeterol twice a day.
The time to first exacerbation was 187 days for tiotropium compared to 145 for salmeterol, representing a 17% reduction in relative risk. Tiotropium was associated with a 14% reduced risk of moderate exacerbation, and a 28% reduced risk of a severe exacerbation requiring hospitalisation.
There was a reduced annual rate of severe exacerbations among tiotropium patients. Overall, the incidence of serious adverse events and of adverse events leading to the discontinuation of treatment was similar in the two study groups.
Current NICE guidelines on COPD state that either a LABA or a LAMA is appropriate if FEV1 is greater or equal to 50% predicted. If FEV1 is less than 50% predicted, then either a LABA plus inhaled corticosteroids in a combination inhaler, or a LAMA is recommended.
Dr Richard Russell, consultant chest physician at Heatherwood and Wexham Park Hospitals and a UK investigator, concluded: ‘At the time the NICE guidelines on COPD were updated there was limited evidence to enable an informed choice to be made between a LAMA or a LABA for first-line maintenance therapy. These results provide the first long-term data to help doctors make this choice.’
Dr Rajiv Sharma, a GP in Bexhill, Sussex and one of the investigators in the UK arm of the trial, said: ‘Preventing hospital admission is one of the big challenges in managing COPD patients. These study results will be valuable in helping GPs make the right treatment decision for patients beyond those highlighted in the NICE guidelines.’
Dr Hunaid Rashiq, a GP in Birmingham with an interest in COPD, said: ‘There is room for drugs affecting well-described pathways, both adrenergic and cholinergic.
‘In my practice our usual regimen involves short-acting beta agonists and long-acting anticholinergics early for symptom relief, with a LABA/inhaled steroid combination added for those with lower FEV1 <50 % and patients whose condition exacerbates regularly. Thus most patients with problematic COPD will probably benefit from both tiotropium and salmeterol in some form.’
Dr Kevin Gruffydd-Jones, a GP in Box, Wiltshire, and a member of the Primary Care Respiratory Society, said: ‘The study shows that tiotropium is very effective at reducing exacerbations, not just improving symptoms. But the NICE guidance should still hold for general practice. One trial does not necessarily alter guidance – it should be about an accumulation of evidence.’
The study, sponsored by Boehringer Ingelheim, the manufacturers of tiotropium, is published in the New England Journal of Medicine.
N Engl J Med 2011; 364:1093-1103
Tiotropium cuts COPD hospitalisation risk by a third