Initial concerns over Spiriva HandiHaler may be unfounded, agency says
THURSDAY, Jan. 14 (HealthDay News) -- The U.S. Food and Drug Administration on Thursday said it found no good evidence that the Spiriva HandiHaler boosts heart risks in patients who use it to help control chronic obstructive pulmonary disease (COPD).
The announcement comes after data released in early 2008 by the drug's maker, "suggesting a small increased risk of stroke in patients treated with tiotropium [Spiriva], the medicine's active ingredient," the FDA noted in a statement.
In October of 2008, the agency released an "Updated Early Communication" that pointed to two other studies suggesting a boost in risk of stroke, heart attack and death among users of the Spiriva HandiHaler.
But a study published in the January 2010 issue of Chest found the opposite: that tiotropium might lower users' risk of heart problems and death.
Spiriva is one of the most commonly prescribed daily treatments for COPD, a progressive respiratory illness combining bronchitis and emphysema that is often linked to smoking. COPD is the fourth-largest killer in the United States.
The Spiriva HandiHaler consists of a capsule used with an inhaler, to be taken once daily. Spiriva is from the class of drugs known as anticholinergics, which also includes the widely used ipratropium bromide (Atrovent).
Thursday's FDA announcement should come as a relief to COPD patients who rely on the Spiriva HandiHaler. In its statement, the FDA said its review of the data does "not support an increased risk of stroke, heart attack, or death in patients using the medicine."
"Today's update is based on an FDA review of the Understanding the Potential Long-Term Impacts on Function with Tiotropium [UPLIFT] study that compared Spiriva HandiHaler with a placebo in 5,992 COPD patients," the agency said. "In November 2009, the FDA Pulmonary-Allergy Drugs Advisory Committee also reviewed the data and voted that findings from the UPLIFT study resolved the potential safety concerns for Spiriva HandiHaler."
The safety status of Atrovent remains unclear, however, because research released Jan. 7 suggested that the drug raises patients' risk for heart attack and heart failure.
"The short-acting form [Atrovent] seems to increase cardiovascular risk, while the long-acting form [Spiriva] seems to decrease it," Dr. Norman H. Edelman, chief medical officer of the American Lung Association, told HealthDay at the time. "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 one of the two studies in Chest, researchers led by Todd A. Lee, from the Hines VA Hospital in Illinois, collected data on almost 83,000 U.S. veterans with COPD. Among these patients, 44 percent 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, more than 6,200 patients had a cardiovascular event: 44 percent suffered heart failure, 28 percent had heart attacks or chest pain, and 28 percent 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 spokeswoman 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."
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 more than 19,500 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 at the time of the study's release. "Tiotropium is by and large a safe medication that can really help most patients with COPD."
Inhaled anticholinergics ease breathing in patients with COPD by preventing the airways from constricting.
Speaking earlier this month, Dr. Neil Schachter, a professor of pulmonary medicine at Mount Sinai Medical Center in New York City, said that 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."
For more information on COPD, visit the U.S. National Heart, Lung, and Blood Institute.
SOURCES: Bartolome Celli, M.D., Caritas-St. Elizabeth's Medical Center, Boston; Norman H. Edelman, M.D., chief medical officer, American Lung Association; Susan Holz, spokeswoman, 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; Jan. 14, 2010, statement, U.S. Food and Drug Administration
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