Inhaler drugs used by millions of people with emphysema and bronchitis may slightly raise the risk for heart attacks and even death, a study suggests.
The results aren't conclusive and inhalers provide significant relief for these patients struggling to breathe. But the study authors urged doctors to closely monitor patients who use the inhalers.
Most affected patients have both emphysema and chronic bronchitis. The condition's formal name, chronic obstructive pulmonary disease, COPD, is the nation's fourth leading cause of death.
The study's increased risks were small, and the drugs' marketer said both medicines are safe. Outside experts called the study compelling but said it has limitations that make it hard to know if the drugs or something else was at fault.
The drugs are tiotropium, sold as Spiriva Handihaler by Boehringer Ingelheim Pharmaceuticals, Inc., and ipratropium, available generically and also sold by Boehringer under the brand name Atrovent.
Spiriva, approved in 2004, and the decade-old Atrovent are used once or more daily to relax muscles and open lung airways. They've been used by 8 million patients worldwide.
A Veterans Affairs study published last week linked ipratropium with an increased risk for heart-related deaths in men.
The new study appears in Wednesday's Journal of the American Medical Association.
The company told the Food and Drug Administration earlier this year that its own data had linked Spiriva with a possible increased risk for strokes. But Boehringer and Pfizer Inc., which jointly market Spiriva, said Tuesday that they had recently given the FDA a new analysis of that data plus new long-term data, which they said shows initial concerns about strokes were unfounded.
"We strongly disagree with the conclusion" in the new study, the companies said in a statement.
COPD affects as many as 24 million Americans and kills more than 100,000 each year. It involves thickened and narrowed lung airways and excess mucous. Symptoms include persistent coughing and severe shortness of breath; smoking is a leading cause.
Patients describe COPD breathing problems as feeling like they're "living the entire day under water, unable to come to the surface," said Dr. Aaron Milstone of Vanderbilt University medical school.
The new study pooled results from 17 randomized studies comparing mostly older patients on either of the drugs with those on different medicine or dummy drugs. Randomized studies are the most rigorous kind of medical research, but Milstone said drawing conclusions from a pooled analysis can be problematic because of differences in patients' characteristics.
It found that using either drug for more than one month appeared to increase chances for fatal and nonfatal heart problems including heart attacks by more than 50 percent.
Among about 7,400 patients on either inhaled drug, 1.8 percent or 135 people developed fatal or nonfatal heart problems over a period of several weeks to several years. By contrast, among about 7,300 patients on other drugs or dummy medicine, 1.2 percent or 86 had those problems.
In absolute terms, out of 40 patients using either drug for one year, there would be one extra drug-linked death, said study author Dr. Sonal Singh of Wake Forest University's medical school.
Other drugs are used for COPD, but they also can have serious side effects, Singh said. This puts patients in "a very tough spot," he acknowledged.
He said before starting drugs, patients should try to reduce heart risks by quitting smoking, keeping blood pressure and cholesterol under control, and using oxygen.
Dr. Mark Rosen, former president of the American College of Chest Physicians and a lung specialist on New York's Long Island, said the data "are very compelling but they're not conclusive."
He said it's unclear what caused the apparent increased risks since the drugs aren't known to affect the heart. The authors said that damaging proteins involved in inflammation are thought to play a role in both COPD and heart disease.
Rosen noted that the analyzed studies weren't designed to look for heart problems, and said it's possible patients on the drugs had more heart problems to begin with.
Still, Rosen said the study "is an excellent reason to do more research to figure out why this is true, if it is true and not a statistical fluke."
