title: Ten years of tiotropium: clinical impact and patient perspectives.
abstract: Tiotropium bromide is an anticholinergic agent that has gained worldwide acceptance as a first-line, once daily maintenance therapy for patients with moderate-to-severe chronic obstructive pulmonary disease. The purpose of this review is to synthesize the evidence base in the past 10 years on the development of tiotropium and its efficacy compared to other able interventions such as long-acting beta agonists (LABAs), as well as to assess its safety profile and its effects on health-related outcomes in patients with COPD. Treatment with tiotropium bromide has generally improved patients' health-related quality of life, reduced the number of patients suffering from acute exacerbations, decreased the number of hospitalizations, improved dyspnea, and reduced adverse events compared to placebo. In the past decade, several studies have examined the safety and efficacy of tiotropium in comparison to placebo and to LABAs (salmeterol, formoterol, and indacaterol) over periods ranging from 3 months to 48 months of follow-up. Head-to-head comparisons of tiotropium 18μg (once daily) with salmeterol 50μg (twice daily) in well-controlled trials demonstrated that tiotropium was superior in reducing acute exacerbation events and in improving quality of life. In a few short-term studies, indacaterol was comparable to tiotropium in its efficacy in improving health-related outcomes. Although the safety record of tiotropium has been exemplary in comparison to placebo, anticholinergic events such as dry mouth can be encountered in some patients. While the long-term safety of tiotropium when delivered in the HandiHaler® has been well documented, its delivery using the Respimat® Soft Mist Inhaler™ was associated with an elevated risk of cardiovascular complications, including increased mortality when compared to placebo. The exact mechanism for this is not known but is being investigated in a large multinational study that will evaluate the long-term safety of different doses of tiotropium delivered by the Respimat® soft mist inhaler versus the HandiHaler®. Further studies are required to investigate the efficacy and safety of tiotropium in comparison with novel LABAs such as indacaterol and vilanterol, and with other emerging novel anticholinergic agents such as aclidinium bromide and NVA237 (glycopyrronium bromide).
authors.affiliation: Manchester Metropolitan University, Department of Health Professions, UK. a.yohannes@mmu.ac.uk
authors.forename: Abebaw M
authors.initials: AM
authors.lastname: Yohannes
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Connolly
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Hanania
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D000420:Albuterol / Q000031:analogs & derivatives / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004417:Dyspnea / Q000188:drug therapy; D004983:Ethanolamines / Q000627:therapeutic use; D000068759:Formoterol Fumarate; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D055118:Medication Adherence; D009079:Mucociliary Clearance / Q000187:drug effects; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011788:Quality of Life; D015363:Quinolones / Q000627:therapeutic use; D000068299:Salmeterol Xinafoate; D012602:Scopolamine Derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D000069447:Tiotropium Bromide
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D007189:Indans; D015363:Quinolones; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; C510790:indacaterol; D000420:Albuterol; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide
keywords: LABA; bronchodilator; chronic obstructive pulmonary disease; indacaterol; salmeterol; tiotropium