The inhalers are bronchodilators
Inhalers prescribed for serious lung disease may increase the risk of deadly heart problems, say researchers.
Trials on more than 15,000 patients found inhaled anticholinergic drugs increased the risk of heart attack, stroke and cardiovascular death by 58%.
The drugs, Atrovent and Spriva, open up the airways to help patients with chronic obstructive pulmonary disease (COPD) to breathe.
The work is published in the Journal of the American Medical Association.
More than two million prescriptions for anticholinergic inhalers were issued in England last year, according to the researchers from the Wake Forest University School of Medicine in the US and the University of East Anglia in the UK.
In the 17 trials that they analysed, long-term use (more than 30 days) of the two anticholinergics ipratropium (Atrovent) and tiotropium (Spiriva) increased the risk of a heart attack by 53% and the risk of cardiovascular death by 80%.
This would mean the drugs could cause one in 40 users to die from a heart condition and one in 174 to have a heart attack, say the researchers.
Risks versus benefits
But they said these risks had to be balanced against the benefits of using an inhaler - they improve patients' quality of life by preventing disease exacerbations and COPD-related hospitalisations.
Anyone with COPD who is benefiting from taking anticholinergic inhalers should not stop taking them based on this study alone."
Judy O'Sullivan, cardiac nurse at the British Heart Foundation
Researcher Dr Yoon Loke said: "It is a relatively small risk - about 3% of users develop problems - but the risk is serious. They may cause heart attacks and death.
"There are alternatives. If you know that your inhaler contains anticholinergics, my advice would be to ask your doctor to prescribe a different inhaler, particularly if you have a history of heart trouble or are at high risk of heart disease."
He said the vast majority of people with COPD are or have been heavy smokers, so they are already at heightened risk of heart attacks.
The current study was unable to determine if these risk factors influenced the findings.
Dr Loke's team started to look at the problem after the manufacturers issued a warning earlier this year through the US Food and Drug Administration that there could be a higher risk of stroke as a result of using these inhalers.
Boehringer Ingelheim said it strongly disagreed with Dr Loke's findings. Its latest analysis of 30 placebo-controlled double-blind, randomised trials with data from 19,545 COPD patients "demonstrated that there is no increased risk of death (all-cause) or death due to cardiovascular events" in patients treated with Spiriva.
Dr Keith Prowse, chairman of the British Lung Foundation, said: "Anticholinergic agents are a very useful and important medication for a large number of people with COPD.
"This study highlights a possible risk of heart attack associated with the medication but the authors acknowledge that there is insufficient data to allow full analysis of other risk factors, including hypertension and pre-existing heart disease, so we need more research to establish accurate levels of risk.
Blue or grey inhalers are 'relievers' and contain bronchodilators to open the airways
There are several different reliever drugs, including beta agonists like salbutamol and anticholinergics like ipratropium
Brown inhalers are 'preventers' and usually contain a steroid drug
"In the meantime, people should discuss any concerns they have with their GP."
Judy O'Sullivan, cardiac nurse at the British Heart Foundation, said: "Anyone with COPD who is benefitting from taking anticholinergic inhalers should not stop taking them based on this study alone."
COPD caused over 27,000 deaths in the UK in 2004, and is projected to be the world's fifth biggest killer by 2020.
Elaine Vickers, research manager at Asthma UK, said: "This research looks solely at people with COPD who, unlike most people with asthma, have irreversible damage to their airways.
"This study looks specifically at medicines not commonly used to treat asthma and if you have asthma it is vital that you take your medicines as prescribed.
"If you have any concerns please speak with your doctor or asthma nurse or call the Asthma UK Adviceline on 08457 01 02 03."