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After completing a review of available tiotropium bromide inhalation powder (Spiriva HandiHaler, Pfizer) data, FDA released an updated communication, stating that in the regulatory body's opinion, available data does not support an association between the use of tiotropium, a commonly prescribed daily treatment for chronic obstructive pulmonary disease, and an increased risk of stroke, heart attack, or cardiovascular death.
After completing a review of available tiotropium bromide inhalation powder (Spiriva HandiHaler, Pfizer) data, FDA released an updated communication, stating that in the regulatory body's opinion, available data does not support an association between the use of tiotropium, a commonly prescribed daily treatment for chronic obstructive pulmonary disease (COPD), and an increased risk of stroke, heart attack, or cardiovascular death.
FDA released 2 previous communications to healthcare professionals, one in March and the other in October of 2009, warning of a potential small but increased risk of stroke (2 cases per 1,000 treated patients), heart attack, and cardiovascular death in those using tiotropium.
These initial communications were in response to data provided by the drug's manufacturer and at least 2 highly visible publications suggesting an increased risk of these adverse events in patients utilizing tiotropium or other inhaled anticholinergic drugs.
This meta-analysis found a greater than 2-fold increased risk of major adverse cardiovascular events with tiotropium (relative risk, 2.12 (95% confidence interval 1.22 to 3.67) compared to control.
In the second publication, investigators from the U.S. Veterans Health Administration conducted a nested case-control study evaluating 32,130 dead and 320,501 surviving COPD patients.
Their study found that those taking ipatropium bromide (an inhaled anticholinergic agent with a shorter duration of action than tiotropium) had an adjusted odds ratio for all-cause mortality of 1.11 (95% confidence interval, 1.08 to 1.15) compared to control.
This later study was printed in the September 16, 2008, volume of the Annals of Internal Medicine.
This January 2010 update of those communications is based on an FDA review of newer data from the Understanding the Potential Long Term Impacts on Function with Tiotropium (UPLIFT) study.
UPLIFT, a 4-year randomized controlled trial, which compared tiotropium with placebo in 5,992 patients with COPD found there was no significant increase in the risk of stroke [relative risk, 0.95 (95% confidence interval 0.70 to 1.29)], heart attack [relative risk, 0.73 (95% confidence interval 0.53 to 1.00)], or cardiovascular death [relative risk, 0.73 (95% confidence interval 0.56 to 0.96)] with tiotropium.
FDA's Pulmonary Allergy Drugs Advisory Committee-a panel of outside experts-met in November 2009, and also concluded that the UPLIFT study attenuated cardiovascular safety concerns associated with tiotropium use.
As a result of their findings, FDA officials are advising healthcare professionals that they can "continue to prescribe [tiotropium] as recommended in the drug label."
FDA. Follow-Up to the October 2008 Updated Early Communication about an Ongoing Safety Review of Tiotropium (marketed as Spiriva HandiHaler) [January 14, 2010]. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm197429.htm. Accessed January 14, 2010.
Singh S, Loke YK, Furberg CD. Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease. JAMA. 2008;300(12):1439-1450.
Lee TA, Pickard AS, Au DH, Bartle B, Weiss KB. Risk of Death Associated with Medications for Recently Diagnosed Chronic Obstructive Pulmonary Disease. Ann Intern Med. 2008.149:380-390.
Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M; UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359:1543-1554.