Leading COPD Drugs Tied to Stroke, Heart Attack

Sept. 24 -- TUESDAY, Sept. 23 (HealthDay News) -- Common drugs prescribed for chronic obstructive pulmonary disease (COPD) are associated with an increased risk of heart attack, stroke and other cardiovascular problems, researchers report.

These inhaled anticholinergic agents, such as Spiriva and Atrovent, are the most commonly prescribed once-daily treatment for COPD, a respiratory illness that's the fourth largest killer in the United States.

"We found a 58 percent increased risk of cardiac death, heart attack or stroke," in people taking these drugs, said Dr. Sonal Singh, assistant professor of internal medicine at Wake Forest University Baptist Medical Center in Winston-Salem, N.C. "In absolute terms, what it means is that if you were to use these drugs for a year, your absolute risk of developing an additional cardiac death would be one in 40."

Singh was lead author of a paper published in the Sept. 24 issue of the Journal of the American Medical Association.

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.

In fact, inhaled tiotropium (Spiriva) is the most widely prescribed drug for COPD, used by more than 8 million patients globally since it was approved by the U.S. Food and Drug Administration in 2002. The second most commonly prescribed drug in this class is ipratropium bromide (Atrovent).

There have been previous scattered reports of an increased risk of cardiovascular events in people using Spiriva, resulting in an "early communication" from the U.S. Food and Drug Administration earlier this year warning of a possible increased risk of stroke with use of the drug.

In the new study, Singh and colleagues conducted a meta-analysis of available studies on inhaled anticholinergic drugs that had been used for the treatment of COPD for at least 30 days. Combined, the studies involved almost 15,000 patients.

They found a 58 percent increased risk of cardiovascular death, heart attack or stroke in participants receiving inhaled anticholinergics.

Use of this class of drugs increased the risk of a heart attack by 53 percent, cardiovascular death by 80 percent and stroke by 46 percent. An increased risk of all-cause death was not clinically significant, but only missed the mark by a small margin, Singh said.

But the makers of Spiriva, Germany-based Boehringer-Ingelheim and Pfizer, based in New York City, took issue with the findings.

"We strongly disagree with the conclusion reached by Singh et al. We have disclosed to regulatory authorities worldwide this important information, which is part of a very robust analysis of all our double-blind, placebo-controlled, parallel group trials with a duration of at least 4 weeks. Our analysis, which includes data from the four-year UPLIFT trial, supports the safety profile of Spiriva," Dr. Andreas Barner, vice chairman of the board of managing directors at Boehringer Ingelheim, said in a statement. "Patients and physicians can be confident that Spiriva is a safe and effective medication," he added.

But Dr. Len Horovitz, a pulmonary specialist at Lenox Hill Hospital in New York City, called the JAMA study results "disturbing," adding that they probably would influence his prescribing practices.

"If someone has a great risk of cardiovascular events, arrhythmias, hypertension, prior heart attack, prior stroke, that's a patient where you probably say, 'I think we're going to try to see how well we can do without this drug,' " he said. "Whereas someone with a clean cardiac history or fewer of these factors, we can say, 'We can do this, but I need to know you're getting such a great benefit from it that you would not be willing to give it up.' "

More information

There's more on COPD at the National Heart, Lung, and Blood Institute.

SOURCES: Sonal Singh, M.D., assistant professor, internal medicine, Wake Forest University Baptist Medical Center, Winston-Salem, N.C.; Len Horovitz, M.D., pulmonary specialist, Lenox Hill Hospital, New York City; Sept. 23, 2008, joint news release, Boehringer-Ingelheim and Pfizer; Sept. 24, 2008, Journal of the American Medical Association