COPD Medicines: Risky or Safe?

Study Links 2 COPD Drugs to Risks of Heart Attack, Stroke, Death

Medically Reviewed by Louise Chang, MD on September 23, 2008
From the WebMD Archives

Sept. 23, 2008 -- Two commonly used treatments for the lung disease known as chronic obstructive pulmonary disease (COPD) boost the risk of heart attack, stroke, or death from cardiovascular causes, according to a new analysis. But the drugs' marketers sharply disagree.

The medicines under scrutiny are called inhaled anticholinergics, which work by relaxing the muscles around constricted airways and relieving symptoms such as shortness of breath.

The use of two commonly prescribed anticholinergics, Spiriva and Atrovent, for more than a month boosted the risk of heart attack, stroke, or dying of cardiovascular problems by 58%, says Sonal Singh, MD, MPH, assistant professor of internal medicine at Wake Forest University School of Medicine in Winston-Salem, N.C., and lead author of the study, which appears in The Journal of the American Medical Association.

Singh and colleagues pooled the results of 17 randomized trials that included nearly 15,000 patients who took the anticholinergics or a control treatment. "Every study points in the same direction," he tells WebMD.

Meanwhile, pharmaceutical industry spokespeople issued a statement strongly disagreeing with the conclusions of the study, issuing their own new analysis that they say confirms the safety of Spiriva.

COPD Medicines: Study Details

Singh and his colleagues looked at the 17 trials to see if the medicines increased the risk of heart attack, stroke, and death from cardiovascular disease or death from other causes.

They found that the COPD medicines increased risk of death from cardiovascular disease as well as the risk of stroke or heart attack when the three outcomes were grouped together, but the drugs did not significantly increase the risk of death from all causes.

While 1.2% of control patients had a heart attack, stroke, or died from cardiovascular disease during the follow-up (which ranged from six weeks to five years), 1.8% of those on the anticholinergics did. That accounts for the 58% increase.

When Singh looked at the individual outcomes, rather than as a group, the increased risk for stroke didn't turn out to be significant, but the risk for heart attack and death from cardiovascular disease remained so.

The latest research isn't the first to uncover the risk. Atrovent was linked with a 34% increased risk of cardiovascular death by other researchers, who published their findings in the Annals of Internal Medicine last week.

COPD Medicines: Industry's View

Both medications are safe, according to spokespeople from pharmaceutical companies that market Spiriva and Atrovent.

"Extensive research provides strong support for the safety of these medications and is contrary to the conclusion expressed in the recently released articles by Dr. Lee and colleagues [the Annals of Internal Medicine study] and Dr. Singh and colleagues," says Lara Crissey, a spokeswoman for Boehringer Ingelheim, which markets Atrovent and jointly markets Spiriva with Pfizer Inc.

In a statement jointly issued by the companies, officials elaborate on Spiriva, saying its safety profile is confirmed by 30 clinical trials recently analyzed by both companies but not yet published.

The statement reads, in part: "The new and expanded safety data contradicts the conclusions about [Spiriva]" in Singh's review.

Citing "data on file" at Boehringer Ingelheim, the statement says the analysis of 30 trials involving nearly 20,000 COPD patients, some on Spiriva, some on placebo, found no increased risk of death from all causes or from cardiac events nor an increased risk of stroke or heart attack.

The data reviewed, according to the statement, includes information from findings of a trial called UPLIFT, to be presented in October at a respiratory society meeting overseas.

Most evidence in the Singh report, the statement also points out, comes from a single study, the Lung Health Study, which involved Atrovent, not Spiriva, and that most deaths from cardiovascular disease occurred among patients who didn't take their medicine.

Singh counters that even after excluding information from the Lung Health Study, the risks remained.

COPD Medicines: Ask Your Doctor

The results of Singh's review are "troublesome," says Norman Edelman, MD, chief medical officer of the American Lung Association and professor of medicine and preventive medicine at Stony Brook University in Long Island, N.Y. "We use anticholinergics a lot," he says of physicians who treat the more than 12 million U.S. adults with COPD.

Until recently, he says, research looked good on both COPD medicines. "Clinical data show people have better lung function on these drugs, especially Spiriva."

Still, he says, "the study doesn't necessarily mean everyone should go off these drugs."

Physicians who care for COPD patients, he says, should read the report carefully and then use their clinical judgment to decide the best treatment.

Other options for treating COPD include inhaled steroids and long-acting bronchodilators, he says, or a combination of treatments. If the COPD is severe, he says, "it is common to take all three."

For COPD patients, he has this advice: "COPD patients should sit with their doctors and say, 'Look, I read this [study], I am concerned about this." Ask the doctor what medicines are best and why, he says.

Show Sources


Singh, S. The Journal of the American Medical Association, Sept. 24, 2008; vol 300: pp. 1439-1450.

Sonal Singh, MD, MPH, assistant professor of internal medicine, Wake Forest University School of Medicine, Winston-Salem, N.C.

Sally Beatty, spokeswoman, Pfizer Inc.

Lara Crissey, spokeswoman, Boehringer Ingelheim.

News release, Boehringer Ingelheim and Pfizer Inc.

Norman Edelman, MD, chief medical officer, American Lung Association, New York; professor of medicine and preventive medicine, Stony Brook University, Long Island, N.Y.

Lee, T. Annals of Internal Medicine, Sept. 16, 2008: vol 149: pp. 380-390.

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