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Last updated on April 17, 2014 at 12:28 EDT

Lung Drugs Might Be Taking Toll on the Heart

September 24, 2008

By Rita Rubin

Widely prescribed drugs recommended as first-line therapy for chronic obstructive pulmonary disease, or COPD — the USA’s fourth-leading killer — raise the risk of heart attacks, strokes and death from heart disease, a study suggests.

COPD refers to two incurable lung ailments, chronic bronchitis and emphysema. Most COPD patients have both. The most common cause is cigarette smoking.

Researchers pooled the results of 17 clinical trials of 14,783 patients that compared the drugs tiotropium or ipratropium with other COPD treatments. The studies followed patients for six weeks to five years.

Tiotropium is sold under the brand name Spiriva. Ipratropium is an older medication that is sold as Atrovent or in combination with another drug as Combivent.

Boehringer Ingelheim, a German company that markets Spiriva with Pfizer, says worldwide sales rose 35% in 2007. Boehringer also makes Combivent, and Pfizer makes Atrovent.

Overall, 1.8% of patients given tiotropium or ipratropium died of cardiovascular disease or had a non-fatal heart attack or stroke, compared with 1.2% of patients on other drugs, a statistically significant difference.

Looking at stroke risk alone, the researchers did not find a statistically significant elevated risk with tiotropium or ipratropium. But the 53% increased risk of heart attack and the 80% increased risk of cardiovascular death were statistically significant, the authors write in this week’s issue of the Journal of the American Medical Association.

For every 40 people who got one of the drugs in a year, there was one extra death, says co-author Curt Furberg, a Wake Forest University epidemiologist. “It’s a big drug, so it’s affecting a large number of people.”

In response to Furberg’s study, Boehringer and Pfizer released a new analysis that had not gone through a journal’s peer review process. It found no increased risk of cardiovascular problems linked to Spiriva.

Last week, a study in the Annals of Internal Medicine found a 34% increased risk of dying from a heart attack or irregular heartbeat in COPD patients using ipratropium, which is in the same class as Spiriva, compared with those using albuterol, another COPD drug, or using nothing. The study focused on veterans diagnosed before Spiriva was approved in 2004.

Lead author Todd Lee, a researcher at Northwestern University’s medical school, says his and Furberg’s studies “raise some important questions about these medications.”

In March, the Food and Drug Administration notified health care professionals that a pooled analysis comparing Spiriva with a placebo revealed a possible increased risk of stroke in patients on the drug. The analysis by Boehringer found that 8 per 1,000 Spiriva patients a year had a stroke, vs. 6 per 1,000 on a placebo.

At the time, the FDA said it had not confirmed the finding. (c) Copyright 2008 USA TODAY, a division of Gannett Co. Inc. <>