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 18 μg (once daily) with salmeterol 50 μg (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).

Cardiovascular safety of new inhaled medications for asthma and chronic obstructive pulmonary disease: a critical review from pharmacist perspective

“…77 The use of the SoftMist® device was associated with increased overall mortality compared to subjects using placebo, LABA, or tiotropium via HandiHaler® (OR 1.51-1.63), and even higher cardiovascular mortality (OR 1.81). [78][79][80] The reason for increased mortality is not yet fully understood, but it is likely to be associated with greater systemic bioavailability, which was found to be dose dependent. On the other hand, a study by Wu YK et al has shown that 5 mcg via SoftMist® inhaler is not associated with significant change of HR variation after 3 months of therapy, compared to 18 mcg via Handihaler®.…”

“…However, these findings should not affect the well-documented long-term safety on the use of tiotropium via Handihaler®. 82,78 …”

Is it possible to improve prognosis in patients with chronic obstructive pulmonary disease?

“…Сегодня препаратами 1 й линии терапии ХОБЛ являются длительно действующие бронходилата торы [6], среди которых наиболее изученным и наи более часто используемым является длительно дейст вующий антихолинергический препарат тиотропия бромид [64]. В многочисленных РКИ подтверждает ся положительное влияние тиотропия бромида на легочную функцию, улучшение клинических симп томов и качества жизни больных, повышение пере носимости физических нагрузок, снижение числа обострений ХОБЛ [64].…”

“…В многочисленных РКИ подтверждает ся положительное влияние тиотропия бромида на легочную функцию, улучшение клинических симп томов и качества жизни больных, повышение пере носимости физических нагрузок, снижение числа обострений ХОБЛ [64]. Кроме того, в открытых по пуляционных исследованиях, РКИ и метаанализах показан положительный эффект тиотропия бромида на прогноз у пациентов с ХОБЛ.…”

New abilities of administration of tiotropium bromide using the aerosol delivery device Respimat®

“…Препаратами 1 й линии тера пии у большинства пациентов с ХОБЛ являются длительно действующие (ДД) бронходилататоры (БД) [1], среди которых наиболее изученным и наи более часто используемым является действующий антихолинергический препарат (АХП) -тиотропия бромид [4,5].…”