Tiotropium is a once-daily, inhaled anticholinergic drug that provides at least 24-hour improvements in airflow and hyperinflation in patients with COPD. Tiotropium bromide capsules for inhalation are co-marketed by Boehringer-Ingelheim and Pfizer under the trade name Spiriva.The NEJM published a randomized, double-blind trial of 4 years of therapy with either tiotropium or placebo in 5993 adults with COPD. Mean age was 65 years and mean FEV1 was 1.32 liters after bronchodilation (48% of predicted value).
A recent meta-analysis published in JAMA that included 14,783 patients with COPD found that patients taking either ipratropium or tiotropium (or both) had a 58% increase in cardiovascular death, heart attack or stroke when compared to patients taking other medications.
There was no increased cardiovascular risk with ipratropium in the NEJM study. Myocardial infarction developed in 67 patients in the tiotropium group and 85 in the placebo group (relative risk, 0.73) and stroke developed in 82 in the tiotropium group and 80 in the placebo group (relative risk, 0.95).
Will JAMA be called the "journal of irreproducible results" one more time?
In the NEJM study, the therapy with tiotropium was associated with improvements in lung function, quality of life, and exacerbations during a 4-year period but did not significantly reduce the rate of decline in FEV1.
The accompanying editorial notes that COPD, similarly to asthma, is a heterogenous disease, or even a group of diseases. "COPD in the singular is probably a misnomer. It is more appropriate to view COPD as a syndrome that encompasses a variety of obstructive diseases that share a common exposure but differ in terms of mechanism of disease and response to therapy."
Mind map of Chronic Obstructive Pulmonary Disease (COPD). See more mind maps at AllergyCases.org.
Mnemonic for treatment modalities in COPD: B CAOS
Bronchodilators
Corticosteroids
Antibiotics and Vaccinations
Oxygen
Smoking cessation
See more mnemomics at AllergyCases.org.
References:
A 4-Year Trial of Tiotropium in Chronic Obstructive Pulmonary Disease. Donald P. Tashkin, M.D., Bartolome Celli, M.D., Stephen Senn, Ph.D., Deborah Burkhart, B.S.N., Steven Kesten, M.D., Shailendra Menjoge, Ph.D., Marc Decramer, M.D., Ph.D., for the UPLIFT Study Investigators. NEJM, 10/2008.
COPD and Declining FEV1 — Time to Divide and Conquer? John J. Reilly, M.D. NEJM, 10/2008.
Chronic Obstructive Pulmonary Disease (COPD). Allergy Cases.
Tiotropium, from Wikipedia, the free encyclopedia.
UPLIFTing News for COPD. Dr. Mintz' Blog.
Data show no stroke risk with Pfizer lung drug: FDA. Reuters.
Images source: Wikipedia, public domain.
Updated: 11/11/2009
Did you get a good sense of the NEJM exclusion criteria for the study? I saw a pretty vague description suggesting any patients that weren't suitable for the study were excluded. If these excluded patients were more likely to have cardiac complications, then perhaps the JAMA study does have a basis.
ReplyDeleteI agree with the above comment.NEJM exclusion citeria included "the presence of a coexisting illness that could preclude participation in the study"....hmm, I wonder how many people with any cardiac conditions were excluded from the study....It seems like they cherry picked the patients who were most likely not to have any cardiac complications.
ReplyDeleteAll studies not focused on cardiac disease have similar exclusion criteria... :)
ReplyDeleteYou want as few confounding variables as possible. This is how the studies are done. It's not real life. This is a controlled environment where you answer a focused question.