In March of 2008, the FDA issued early communication about a possible connection between Spiriva Handihaler and an increased risk of stroke. Spiriva Handihaler which is manufactured by Boehringer Ingelheim and marketed by Pfizer has been used as a once-daily treatment for bronchospasm associated with COPD (chronic obstructive pulmonary disease), including chronic bronchitis and emphysema.
According to results pooled from 29 different clinical trials, individuals treated with Spiriva for one year may face an increased risk of stroke versus those who were given the placebo. The 29 clinical studies included approximately 13,500 patients with COPD. Based on the data from these studies, the preliminary estimates of the risk of stroke are 8 patients per 1000 patients treated for one year with Spiriva, and 6 patients per 1000 patients treated with placebo. This means that the estimated excess risk of any type of stroke due to Spiriva is 2 patients for each 1000 patients using Spiriva over a one year period.
In a JAMA article 9-24-09, overall meta-analysis of 12 randomized controlled trials found 58 major cardiovascular events from inhaling tiotropium vs. 41 for the control group. However, the causation science is still under investigation and we’re anticipating an FDA analysis of the UPLIFT study data which is projected to take several months.
From the JAMA article 9-24-08 on inhaled anticholinergics, including tiotropium:
Conclusions: Among individual components of the primary end point, inhaled anticholinergics significantly increased the risk of MI and Cardiovascular death without a statistically significant increase in the risk of stroke. All cause mortality was reported in 149 of the patients treated with inhaled anticholinergics and 115 of the control patients. A sensitivity analysis restricted to 5 long-term trials confirmed the significantly increases risk of cardiovascular death, MI or stroke of patients treated with anticholinergics vs 1.8% of the control patients. Conclusion: Inhaled anticholinergics are associated with a significantly increased risk of cardiovascular death, MI or stroke among patients with COPD.
From Pfizer’s flack Prof. Dr. Marc Decramer, Lead Investigator in the UPLIFT study:
The data from UPLIFT indicate that tiotropium does not increase the risk of death, cardiovascular death, myocardial infarction and stroke. Furthermore, examination of all serious cardiac and all serious lower respiratory tract adverse events indicates that tiotropium is associated with a decreased risk of experiencing a serious adverse event in these organ classes.
FDA Rethinks Spiriva Stroke Warning Spiriva Inhaler Not Linked to Stroked, New Study Suggests By Daniel J. DeNoon WebMD Health News Reviewed by Louise Chang, MD
October 9th, 2008- The FDA is reconsidering its recent warning that the lung disease drug Spiriva might raise stroke risk. The warning came after Spiriva maker Boehringer Ingelheim analyzed pooled data from 29 Spiriva studies. These studies suggested that fro every 1000 patients taking Spiriva, there were two extra cases of stroke. Now there’s new data from the four-year UPLIFT study of some 6,000 patients with COPD. The patients, average age 65, took Spiriva or placebo in addition to other types of respiratory drugs. There were 82 strokes among the 2,987 patients taking Spiriva and 80 strokes among the 3,006 patients taking an inactive placebo. The difference is not statistically significant. The FDA says it will take several months for it to finish its review of the huge amount of data from the UPLIFT study. At that time, the federal agency says it will release all existing data of Spiriva and stroke risk.