Comparative mortality risk of tiotropium administered via handihaler or respimat in COPD patients: are they equivalent?
BACKGROUND
Tiotropium bromide, once daily, long-acting anticholinergic bronchodilator is either administered by handihaler metered dose inhaler or by respimat soft mist inhaler. It has been proved to improve lung function, daily symptoms and quality of life and to decrease the exacerbation and hospitalisation rate of patients with Chronic Obstructive Pulmonary Disease (COPD). Although the efficacy of both formulations is undeniable, concerns have been raised on their effect on cardiovascular and general mortality.


METHODS
Two independent authors systematically reviewed Medline, Scopus, Cochrane Library and ClinicalTrials.gov to collect clinical trials, observational studies and meta-analyses studying the safety of tiotropium. The reference list of all the included studies were also reviewed.


RESULTS
Limited, early studies suggested a potential increase in cardiovascular and general mortality associated with tiotropium handihaler, but these data were outweighed by following larger trials, real-life studies and meta-analyses which proved the opposite. On the other hand, data on tiotropium respimat (5 μg) have been contradictory, with different studies suggesting increased cardiovascular and general mortality compared to handihaler (18 μg) or placebo, especially in patients with comorbid diseases. TIOSPIR trial suggests comparable safety of the two formulations. However the exclusion of patients with pre-existing unstable cardiovascular disease, moderate or severe kidney disease or any other significantly disease may limit the generizability of these results.


CONCLUSIONS
Although the two tiotropium formulations have similar efficacy, current data cannot prove safety equivalence, since respimat may be associated with increased cardiovascular and general mortality, especially in patients with comorbid diseases.
Chest Centre, University Hospital Aintree, Liverpool, UK; Respiratory Assembly, Hellenic Society for The Advancement of Biomedical Research, Athens, Greece. Electronic address: a.mathioudakis@nhs.net.
Alexander G
AG
Mathioudakis
Respiratory Assembly, Hellenic Society for The Advancement of Biomedical Research, Athens, Greece.
Victoria
V
Chatzimavridou-Grigoriadou
Respiratory Assembly, Hellenic Society for The Advancement of Biomedical Research, Athens, Greece; Respiratory Department, General Hospital of Nikaia St. Panteleimon, Piraeus, Greece.
Efstathia
E
Evangelopoulou
Respiratory Assembly, Hellenic Society for The Advancement of Biomedical Research, Athens, Greece; Respiratory Department, IASO General Hospital, Athens, Greece.
Georgios A
GA
Mathioudakis
Department of Thoracic Medicine, University of Crete, Greece.
Nikolaos M
NM
Siafakas
D000280:Administration, Inhalation; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality; D006801:Humans; D036501:Metered Dose Inhalers; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D011788:Quality of Life; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000069447:Tiotropium Bromide
D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide
COPD; Human; Respimat; Safety; Systematic review; Tiotropium