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Cardiovascular Safety of Inhaled Anticholinergic Agents for COPD
Two new analyses of tiotropium and ipratropium yield different results.
A controversy has developed that involves the inhaled anticholinergic agents ipratropium (Atrovent) and tiotropium (Spiriva). In a 2008 meta-analysis of randomized trials in patients with chronic obstructive pulmonary disease, these drugs were associated with excess risks for cardiovascular death and myocardial infarction (JAMA 2008; 300:1439). However, this meta-analysis did not include the UPLIFT trial — the largest and longest-term trial of tiotropium to date — which was published in 2009 (JW Gen Med Oct 27 2009). In UPLIFT, tiotropium was associated with significantly fewer serious cardiovascular events than was placebo.
Now, in a new analysis funded by the maker of tiotropium, researchers have pooled patient-level data from all placebo-controlled tiotropium trials of at least 4 weeks' duration (including UPLIFT). This analysis demonstrates a significant 17% relative reduction in a composite endpoint of serious cardiovascular events and shows no excess mortality.
However, in a new cohort study, researchers used a Veterans Administration database to examine cardiovascular risk among almost 83,000 COPD patients; about half were using ipratropium. In analyses controlled for various confounding factors, exposure to ipratropium was associated with 30% greater risk for adverse cardiovascular events than was no exposure.
Comment: The new tiotropium analysis provides reassurance that tiotropium does not cause adverse cardiovascular events, although this conclusion is tainted somewhat by industry funding of this work. The VA cohort study of ipratropium is provocative but has potential for considerable residual confounding. For now, many experts believe that patients can reasonably continue to use anticholinergic inhalers if their symptoms clearly improve with these agents.
Published in Journal Watch General Medicine February 2, 2010
Citation(s):
Celli B et al. Cardiovascular safety of tiotropium in patients with COPD. Chest 2010 Jan; 137:20.
- Original article (Subscription may be required)
- Medline abstract (Free)
Ogale SS et al. Cardiovascular events associated with ipratropium bromide in COPD. Chest 2010 Jan; 137:13.
- Original article (Subscription may be required)
- Medline abstract (Free)
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