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Ipratroprium cardiac risks not proven in trials

Your story about research in Chest raised concerns that the short-acting bronchodilator ipratropium might increase cardiac risk (‘COPD inhaler raises cardiac risk by 40%').

The study is based on data from a cohort study of 82,717 US veterans. Cohort studies can be valuable for identifying safety signals arising from use of medication, but there are many potential biases and confounders, and results should always be interpreted cautiously. The veterans study does not provide reliable data on COPD severity or smoking, which are both associated with ischaemic heart disease.

Ipratropium's safety profile is well understood as the drug has been licensed for many years. Its summary of product characteristics does not contain any contraindications or cautions for cardiac disease. It lists the following possible adverse events under the heading of cardiac disorders:

• tachycardia – uncommon

• palpitations – rare

• supraventricular tachycardia – rare

• atrial fibrillation – rare.

It has been postulated there is a raised risk of cardiovascular events within six months from first-time use of ipratropium. This risk has not been shown in randomised clinical trials, which include anticholinergic-experienced patients.

Tiotropium is a once-daily anticholinergic medication licensed for treatment of COPD. Tiotropium trials have shown favourable clinical outcomes in COPD when compared with ipratropium. As the medicines share a similar mechanism of action it is likely their safety profiles will also be similar.

There is recent high-quality data available for tiotropium from randomised clinical trials that is appropriate to examine. UPLIFT, a four-year study of almost 6,000 patients, showed a decreased risk for fatal cardiovascular events in patients on tiotropium (0.8 reduced risk).

Data from a recent analysis of adverse event reporting from 26 phase III and IV tiotropium clinical trials involving 17,014 patients was reassuring about the safety of tiotropium, which was associated with a reduced risk for a composite endpoint of major adverse cardiovascular events.

Recently the US Food and Drug Administration pulmonary-allergy drugs advisory committee voted affirmatively that data from UPLIFT adequately addressed the potential safety concern for an increased risk of stroke or adverse cardiovascular events.

This verdict is good news for both patients and prescribers.

Dr Kevin Curry
Senior medical adviser (respiratory), Boehringer Ingelheim


Ogale SS, Lee AL, Au DH, et al. Cardiovascular Events Associated With Ipratropium Bromid. Chest 2010;137:13-19.

Tashkin DP, Celli B, Senn S et al. A 4-Year Trial of Tiotropium in Chronic Obstructive Pulmonary Disease. N Eng J Med 2008;359:1143-54.

Kesten S, Celli B, Decrame M et al. Tiotropium HandiHaler in the treatment of COPD. A safety review. Int J of COPD 2009;4:397-409.

Summary Minutes of the Pulmonary-Allergy Drugs Advisory Committee. November 19, 2009. Available at (Last accessed 11th January 2010)

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