Previous pooled analyses suggested that tiotropium is associated with a higher risk of mortality than placebo when delivered via the Respimat soft-mist inhaler (at a dose of 5 microgram daily), but a reduced mortality risk relative to placebo when administered via the breath-actuated HandiHaler (at a dose of 18 microgram daily).
The prescribing information for Spiriva Respimat had therefore recommended caution when prescribing the anticholinergic to patients with known cardiac rhythm disorders.
Now, however, the randomised, controlled double-blind TIOSPIR trial (n=17,135) has shown that there is no significant difference between the two treatments in terms of safety (hazard ratio for death from any cause for tiotropium Respimat vs tiotropium HandiHaler, 0.96; 95% CI 0.84-1.09) or efficacy (hazard ratio for first COPD exacerbation, 0.98; 95% CI 0.93-1.03) in the treatment of COPD.
The prescribing information for both products has been updated to advise prescribers to consider the risk of cardiovascular side-effects in patients with conditions that were excluded from the TIOSPIR trial and could be affected by the anticholinergic action of tiotropium, including:
- myocardial infarction in the last 6 months
- unstable or life-threatening cardiac arrhythmia
- cardiac arrhythmia requiring intervention or a change in drug therapy in the past year
- hospitalisation for heart failure (NYHA Class III or IV) within the past year
These patients should be advised to report any worsening of cardiac symptoms during treatment.
In addition, treatment should be regularly reviewed in patients at high risk of cardiovascular events.