COPD Drugs Linked To Cardiovascular Risk

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Main Category: Respiratory / Asthma
Article Date: 24 Sep 2008 - 1:00 PDT

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Researchers in the US and UK reviewed published evidence on the widely prescribed anticholinergics ipratropium bromide and tiotropium bromide (marketed as Atrovent and Spiriva), and found they were linked to significantly increased risk of cardiovascular death, heart attack and stroke among patients with chronic obstructive pulmonary disease (COPD), a condition that includes chronic bronchitis and emphysema.

The study was the work of scientists from the Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA, and the University of East Anglia, Norwich, England, UK, and is published in the September 24 issue of the Journal of the American Medical Association, JAMA.

Anticholinergics are inhaled drugs that are widely prescribed to treat patients with COPD, but until this study their effect on cardiovascular risk was not known, wrote the authors, who conducted systematic searches of well known publications databases in March this year for all relevant articles published up to that date. Their search included directories such as MEDLINE and the Cochrane Database, plus articles held on regulatory databases in the US and the UK. They also searched manufacturers' trial registries.

The researchers then conducted a meta-analysis of pooled data from all the studies they found on inhaled anticholinergic for treatment of COPD that were randomized, controlled trials where treatment lasted for at least 30 days and outcome measures included cardiovascular events. For the meta-analysis the primary outcome measure was a combination of cardiovascular death, heart attack or stroke. The secondary outcome measure was death from any cause.

In total, the authors found 103 articles, from which they selected 17 trials with a total of 14,783 participants, according to their inclusion criteria. The follow up period ranged from 6 weeks to 5 years.

The findings revealed that taking inhaled anticholinergics for at least six weeks significantly boosted the risk of cardiovascular death, heart attack or stroke by 58 per cent. They also showed that:

• Cardiovascular death, heart attack (MI) or stroke occurred in 135 of 7,472 patients (1.8 per cent) that were on inhaled anticholinergics.


• This compared with 86 of 7,311 controls (1.2 per cent).


• Looking at the individual outcomes, being on inhaled anticholinergics was linked to a statistically significant 53 per cent higher risk of having a heart attack and a statistically significant 80 per cent higher risk of cardiovascular death.


• However, although being on inhaled anticholinergics was calculated to show a 46 per cent higher risk of stroke, this was not statistically significant.


• A further sensitivity analysis of the long term trials only (lasting more than 6 months), confirmed the significantly increased risk of cardiovascular death, heart attack or stroke among patients taking anticholinergics versus controls.

The authors concluded that:

"Inhaled anticholinergics are associated with a significantly increased risk of cardiovascular death, MI, or stroke among patients with COPD."

In a press statement reported by WebMD, Boehringer Ingelheim, a German company that markets Atrovent (ipratropium bromide) and also markets Spiriva (tiotropium bromide) with Pfizer, disputed the study's findings and said both drugs were safe. They said a yet to be published analysis of 30 trials covering more than 20,000 patients showed Spiriva did not increase risk of cardiac death or death from all causes, and neither did it increase risk of heart attack or stroke compared to placebo.

The chief medical officer of the American Lung Association, Dr Norman Edelman, told WebMD that COPD patients who are worried about this study should talk to to their doctors. He called the results "troublesome" and said there were some 12 million Americans being treated for COPD, a lot with anticholinergics.

"Inhaled Anticholinergics and Risk of Major Adverse Cardiovascular Events in Patients With Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis."
Sonal Singh; Yoon K. Loke; Curt D. Furberg.
JAMA. 2008;300(12):1439-1450.
Vol. 300 No. 12, September 24, 2008.

Click here for Abstract.

Source: journal abstract, WebMD.

Written by: Catharine Paddock, PhD




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