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Triple COPD therapy reduces risk of death by 35%

Combination triple therapy reduces mortality, hospital admissions and exacerbations in patients with COPD, new UK research shows.

Researchers argued GPs commonly use triple therapy with inhaled corticosteriods, beta-agonists and antimuscarinics for COPD ‘with only limited scientific support' - but that their study supported the strategy.

NICE guidance published in 2010 suggests a stepwise approach to the use of drugs for patients with COPD where short-acting beta-agonists or short-acting muscarinics are used first, with inhaled corticosteroids reserved for those who experience exacerbations or persistent breathlessness and have a forced expiratory volume (FEV) of less than 50% and long-acting muscarinics added if patients are still not controlled on dual therapy.

In the first study of real-life outcomes of the treatment regime on mortality, hospital admissions and exacerbations, patients diagnosed with COPD in the NHS Tayside Respiratory Disease Information System between 2001 and 2010 were studied. 

Patients were divided in two groups based on their use of dual or triple therapy and a statistical analysis used to calculate hazard rations for all-cause mortality hospital admissions due to respiratory disease, and emergency oral steroid use, to treat exacerbations.

Some 1,857 patients were prescribed triple therapy – any combination of an inhaled steroid, a long-acting beta-agonist and tiotropium – while 996 were prescribed dual therapy with an inhaled steroid and a long-acting beta-agonist, but the triple therapy group had more severe COPD and a lower mean FEV1, at 50.8% predicted, compared with 62.7% in the dual therapy group. Mean follow-up lasted 4.7years.

After adjusting for corvariates including history of disease, smoking, age, sex and deprivation, the addition of tiotropium to dual therapy reduced the risk of death from any cause by 35%.

A subgroup analysis to determine if there was any reduction in the risk of death due to respiratory or cardiovascular disease showed adding the third drug reduced the risk of death from respiratory disease by 30% and from cardiovascular disease by 51%.

The risk of COPD exacerbations was reduced by 29%, while the risk of being admitted to hospital due to respiratory disease was 15% lower in patients prescribed triple therapy compared with dual therapy.

But there were no clinically relevant changes found in lung function between the two groups.

Study leader Professor Brian Lipworth, professor of allergy and pulmonology at the University of Dundee, concluded: ‘To our knowledge we have conducted the first retrospective cohort study directly comparing the additive benefits of tiotropium to combination therapy with ICS and LABA.'

‘We have demonstrated, through a retrospective observational study beneficial effects on all-cause mortality, hospital admissions due to respiratory disease and oral corticosteroid use with the use of inhaled corticosteroids, LABAs and tiotropium versus inhaled corticosteroids and LABA therapy.'

‘We believe that our findings merit discussion as they address real-life outcomes with a long period of follow up and we believe are as valid as a randomised controlled trial where patient compliance is artificially enforced and there are rigid inclusion and exclusion criteria.'

The study is published online in the Journal Chest.