QUESTIONS & ANSWERS: Regarding Meta‐analysis Report Concerning Inhaled Tiotropium (Spiriva®)
December 31, 2008
On Wednesday, September 24th, 2008, the COPD Foundation hosted a teleconference with Dr. Byron Thomashow, Chairman of the COPD Foundation Board of Directors, and Dr. Dave Balazar of Boehringer‐Ingelheim Pharmaceuticals, to answer questions regarding the day’s release of a meta‐analysis report in the Journal of the American Medical Association (JAMA) concerning inhaled tiotropium, marketed as Spiriva®, which is a long‐acting inhaled anticholinergic agent used in managing COPD. Over 50 individuals representing various sectors of the COPD patient community were present in the conference, and asked several questions to the two experts.
In regards to the study released, the COPD Foundation issued a statement:
“Inhaled anticholinergic medications have been an important agent in COPD care for many years. All available guidelines stress the importance of maintenance therapy in COPD patients with moderate, severe, or very severe disease. Inhaled tiotropium, a long‐acting inhaled anticholinergic agent, has been a mainstay of COPD care. The meta‐analysis published in JAMA on September 24th raises concerns over cardiovascular risks. However, meta‐analysis of aggregate published data does have limitations and it must be stressed that COPD itself has been defined as a cardiovascular risk factor. UPLIFT®, one of the largest trials ever done in COPD has recently been completed. While the results of this very large study will not be available until next month, the UPLIFT® safety data released today report no increased cardiovascular risk. The COPD Foundation would suggest caution in potentially over‐reacting to the JAMA study. COPD is almost always a preventable and treatable disease. Available data continues to suggest that tiotropium is an important component of that therapy. We await with interest and hope, the full results of UPLIFT®.” (By Dr. Byron Thomashow, Chairman of the COPD Foundation Board of Directors.)
The following is a Questions and Answers document listing the questions asked and answered on the teleconference. These answers are for your reference only, so please consult your doctor before making any changes to your treatment regimen.
QUESTIONS & ANSWERS
Question: What did the article in the Journal of the American Medical Association say about Spiriva®?
Answer: The meta‐analysis raised concerns that inhaled anticholinergic agents like ipratropium and tiotropium could increase cardiovascular risks.
Q: What is the UPLIFT® Study?
A: The UPLIFT® study is a very large study of almost 6,000 COPD patients looking at the impact of tiotropium.
Q: Will the UPLIFT® data be able to tell us how many patients, who didn’t have a recent event but have a history of cardio vascular disease and cerebral vascular disease, are at greater risk for having such problems if they take Spiriva®?
A: Yes. Those types of analyses will be done once the UPLIFT® study information becomes available.
Q: The article in JAMA states that cardiovascular death is a more frequent form of death in patients with COPD than with respiratory causes. Is that correct?
A: Cardiovascular risk is very real in COPD. The data is clear that COPD is an independent risk factor for cardiovascular disease. According to the study conducted by Mannino, et al in 2003, in patients with mild or moderate COPD, cardiovascular disease was the prominent cause of death, significantly more prominent cause of death than COPD. And the more severe the COPD the more likely the death will be related to COPD, but even in the severe stage COPD group, cardiovascular deaths are almost equal in prominence.
Q: Could the JAMA article have been skewed partly because of the problems that are comorbidity to COPD?
A: COPD is frequently associated with multiple co‐morbidities. COPD is the 4th leading cause of death in the U.S., and the mortality data on COPD shows that many of those risks are cardiovascular. It may well be that those individuals with COPD have similar risk factors for cardiovascular disease, and could indeed have cardiovascular disease. That, however, does not answer all the questions. Therefore, if you do need to use a medicine and tiotropium is a very good medicine, you should use it with care and talk with your doctor.
Q: Didn’t something similar happen recently regarding Spiriva®?
A: Yes. In March of this year, Food and Drug Administration (FDA) communicated concerns over an imbalance of strokes presented in the preliminary data submitted by Boehringer‐Ingelheim Pharmaceuticals on Spiriva®. Safety investigations were conducted, but due to the lack of verifiable data, and with the pending results of the UPLIFT® study, the FDA decided to review the concern once the new study data became available.
Q: Are there any other medications that are commonly used by individuals with COPD that may aggravate the disease?
A: It is well known that all medicines have potential safety issues. Therefore to be very careful and know full well the medications you use. It is also important to always talk to your doctor about whether or nor the treatment is appropriate and about other medical conditions you may have.
Q: What other drugs contain tiotropium and ipratropium?
A: There are no other drugs that mix them. Currently, ipratropium (brand named Atrovent®) is combined with a short‐acting beta‐agonist, brand name Combivent®. There is no other drug that has been combined in a single agent with tiotropium. Ipratropium is also part of Duoneb® with a nebulized beta‐agonist. There are a number of relatively recently approved long‐acting nebulized beta‐agonists that are available, and over the course of the next several years, there will be many new tiotropium‐like drugs and combination drugs. Several pharmaceutical companies are working on putting together long‐acting beta‐agonists, long‐acting anticholinergics, and inhaled corticosteroids in a
long‐acting single agent.
Q: Is it OK for me to use ipratropium (Combivent®, Atrovent®) as well as tiotropium (Spiriva®)?
A: In order for tiotropium to work it has to get to the spot where it can bind, and research has suggested is that if you use a short‐acting anticholinergics like ipratropium, it can preferentially bind and block, preventing the tiotropium to fully function. While there are some safety concerns from potentially combining these agents, there are also concerns about how effective the drug is going to be. The recommendations are not to combine tiotropium and ipratropium.
Q: How do you expect prescribing physicians will react to this study’s information if they are the first ones to see it? Will they take their patients off this treatment?
A: It is impossible to predict how physicians will react. That is why it is very important to spread all of the information about this study and the pending results of the UPLIFT® study.
Q: How is it planned to get the word out to the public that the results of the UPLIFT® study contradict the study published in JAMA?
A: COPD is a disease that for a long, long time has been misrepresented or it is certainly a disease that has been surrounded by misconception. For the longest time, the general perception was that this was a disease of old men, and that is clearly not true. It is a disease of men, and it is a disease of women. It is a disease of the middle‐aged, and it is a disease of the working people. For the longest time the perception has been out there that this is the fault of the patients with the disease because of their smoking. While most people with COPD did smoke, only a small fraction of smokers develop significant COPD, demonstrating that there are other factors either generic or environmental that cause COPD.
That’s why it is important to get beyond the “shame and blame.” The perception has been that this is not a treatable or that it is a poorly treatable disease, and that’s not true. Therefore the COPD Foundation is committed to presenting all relevant information that affects individuals with COPD, whether or not the interests match those of the pharmaceutical industry. The Foundation will publish the findings of the UPLIFT® study on the website and COPD Digest, and be available by phone through C.O.P.D. Information Line as soon as it published.
If you have additional questions you’d like to submit to Dr. Thomashow in regards to the study published in JAMA about tiotropium, send an email with “Q&A for Dr. Thomashow” in the subject line to .