Leading COPD Drug May Raise Chances of Heart Trouble

By Steven Reinberg
HealthDay Reporter

THURSDAY, Jan. 7 (HealthDay News) -- New research suggests that the drug ipratropium bromide (Atrovent), used widely among patients who have chronic obstructive pulmonary disease (COPD), may raise the risk of heart attack and heart failure, while a separate study of the COPD drug tiotropium (Spiriva) shows it may well lower the risk of heart problems and death.

The inhaled medications are the most commonly prescribed daily treatments for COPD, a respiratory illness that's the fourth-largest killer in the United States. The two studies are published in the January issue of Chest.

"The short-acting form [Atrovent] seems to increase cardiovascular risk, while the long-acting form [Spiriva] seems to decrease it," said Dr. Norman H. Edelman, chief medical officer of the American Lung Association. "It is important to point out, however, that the difference is an indirect inference," he added.

"To prove beyond scientific doubt that the two forms of anticholinergic drugs are different in this or other ways there would have to be a head-to-head comparison; a study which is not likely to be done," Edelman said.

In the first study, researchers led by Todd A. Lee, from the Hines VA Hospital in Illinois, collected data on 82,717 U.S. veterans with COPD. Among these patients, 44% were using Atrovent at some point during the study.

Those patients were followed until they had a cardiovascular event, died or until the study's end in September 2004. During the follow-up, 6,234 patients had a cardiovascular event: 44% suffered heart failure, 28% had heart attacks or chest pain, and 28% had irregular heart rhythms, the researchers reported.

Lee's team also found that during the first six months of Atrovent therapy, patients were at an increased risk for these cardiovascular events, although those who took the drug for more than six months without an incident did not have an increased risk of heart attack or heart failure.

"These findings are consistent with previous concerns raised about the cardiovascular safety of ipratropium bromide," the researchers concluded.

Boehringer Ingelheim, the makers of Atrovent, said the drug is safe and the latest findings do not prove there is an increased risk of heart failure or other heart-related problems associated with the drug.

"Atrovent has been widely used in the U.S. for more than 20 years," said company spokeswomen Susan Holz. "The findings described in the paper are not consistent with the Boehringer Ingelheim clinical trial and safety database for Atrovent, which do not support evidence of an increased risk for cardiovascular events among patients using Atrovent."

However, Dr. Sonal Singh, an assistant professor of internal medicine at Wake Forest University Baptist Medical Center in Winston-Salem, N.C., disagreed.

"The current study on ipratropium confirms our previous assessment on the cardiovascular risks of inhaled anticholinergics with the short-acting ipratropium," he said.

In the second paper, Dr. Bartolome Celli, from Caritas-St. Elizabeth's Medical Center in Boston, and colleagues looked at the results of 30 clinical trials that included 19,545 patients, some of whom received Spiriva while others were given a placebo.

The researchers found patients taking Spiriva had a lower risk of dying compared with patients receiving placebo. In addition, those taking Spiriva had fewer respiratory events. This study was funded by the pharmaceutical giants Boehringer Ingelheim and Pfizer.

"There is a benefit of tiotropium in terms of mortality when data from all of the trials with tiotropium are pooled together. This is in contrast to a previous scare that anticholinergics could be associated with poor outcomes," Celli said. "Tiotropium is by and large a safe medication that can really help most patients with COPD."

However, Singh voiced doubts about the findings. "A significantly increased risk of mortality and cardiovascular events has been reported with tiotropium Respimat inhaler in several year-long trials," he said.

"The concomitant use of short-acting inhaled anticholinergics, the incomplete reporting of nonfatal cardiovascular events such as heart attack and mortality in one trial, and the fact that none of these trials were designed to measure cardiovascular risk means that the cardiovascular safety of tiotropium remains uncertain and requires a thorough investigation by independent investigators," Singh said.

COPD is a progressive, destructive disease of the lungs, usually brought on by smoking, for which there's no known cure. Symptoms include restricted breathing, secretion of mucus, oxidative stress and inflammation of the airway.

Inhaled anticholinergics ease breathing in patients with COPD by preventing the airways from constricting.

Dr. Neil Schachter, a professor of pulmonary medicine at Mount Sinai Medical Center in New York City, said the risks of these drugs remains unclear.

Schachter added that he isn't going to "change any of my prescribing habits at this point." He currently prescribes Spiriva more often than Atrovent.

"Spiriva is certainly a very useful drug," he said. "My personal experience is that it has relatively few side effects. It is generally well-tolerated, and patients seem to have a good response to it."

However, he doesn't see a reason not to prescribe Atrovent for some patients.

For people with severe COPD, Schachter prescribes a combination of three drugs including Spiriva plus a long-acting beta-agonist and a steroid.

"Many of these patients are desperate," he said. "However, you have to be cautious and do the best for the patient you have."

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COPD (chronic obstructive pulmonary disease) is the same as adult-onset asthma. See Answer

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SOURCES: Bartolome Celli, M.D., Caritas-St. Elizabeth's Medical Center, Boston; Norman H. Edelman, M.D., chief medical officer, American Lung Association; Sonal Singh, M.D., assistant professor, internal medicine, Wake Forest University Baptist Medical Center, Winston-Salem, N.C.; Susan Holz, spokeswomen, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Conn.; Neil Schachter, M.D., professor, pulmonary medicine, Mount Sinai Medical Center, and director, Mount Sinai COPD Program, New York City; January 2010, Chest