Comparative Safety of Long-Acting Inhaled Bronchodilators

Jara, Michele; Lanes, Stephan; Wentworth, Charles; May, Corey; Kesten, Steven

doi:10.2165/00002018-200730120-00007

Cited by 39 publications

(8 citation statements)

References 24 publications

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“…Bronchodilators are the primary treatment for COPD and include anticholinergics, β 2 -agonists, methylxanthines, and corticosteroids used alone or in combination. 1 The effectiveness and safety of long-acting anticholinergic agents (LAACs) and long-acting β 2 -adrenergic receptor agonists (LABAs) have been described in meta-analyses 2 , 3 or retrospective cohort studies, 4 , 5 reporting an imprecise reduction in mortality and a significantly lower risk for COPD exacerbations. Accumulated evidence has shown that a combination of LAAC and LABA is effective in improving lung function tests and quality of life compared with monotherapy in patients with COPD, particularly when the COPD is severe.…”

Section: Introductionmentioning

confidence: 99%

Long-acting Inhaled Bronchodilator and Risk of Vascular Events in Patients With Chronic Obstructive Pulmonary Disease in Taiwan Population

et al. 2015

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A combination of long-acting anticholinergic agents (LAACs) and long-acting β2-adrenergic receptor agonist (LABA) is effective in improving lung function in chronic obstructive pulmonary disease (COPD) compared with monotherapy. However, evidence on whether this combination increases the incidence of stroke or other cardiac events remains sparse. The objective of the present study was to investigate the incidence of stroke and other cardiovascular diseases in COPD patients treated with LAAC, LABA, or a combination of the 2.We conducted this population-based study using the Taiwan National Health Insurance Research Database (1997–2008), identifying COPD patients and their prescribed medication from the International Classification of Disease, Ninth Revision codes 490–492 or 496. A multivariate Cox proportional-hazards model was used to compare the risk of stroke and other cardiovascular diseases over the 11-year period after treatment with LAAC or LABA only or in combination.Of the 596 COPD patients (mean age 70 y), 196 were treated with LAAC, 318 with LABA, and 82 were treated with a combination. The overall incidence of stroke (8.53%) significantly increased in the combination group compared with LAAC (2.04%) or LABA (1.26%) only. In the Cox regression analysis, the adjusted hazard ratio over the 11-year survey period for stroke in patients treated with the combination compared with LABA only was 1.04 (95% confidence interval, 1.06–2.99) and for LAAC, it was 0.31 (95% confidence interval, 0.02–2.32).This cohort study using a large health insurance database showed that treating patients with COPD, with a combination of LAAC and LABA, may be associated with an increased hazard of stroke compared with treatment with either agent alone. We should be particularly cautious about comedication of LAAC and LABA in patients with COPD.

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Section: Introductionmentioning

confidence: 99%

Long-acting Inhaled Bronchodilator and Risk of Vascular Events in Patients With Chronic Obstructive Pulmonary Disease in Taiwan Population

et al. 2015

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“…Observational studies regarding mortality and inhaled anticholinergics have been reported; however, in general suffer from inability to adequately adjust for confounding by severity and diagnosis 44,45. As well, conflicting results have been reported, with increases, decreases and similar rates of events compared to control groups, which reflects differing methodologies but similar limitations 44–47.…”

Section: Discussionmentioning

confidence: 99%

Tiotropium HandiHaler® in the treatment of COPD: A safety review

Kesten¹

2009

COPD

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BackgroundTiotropium is a long-acting inhaled anticholinergic developed for the treatment of chronic obstructive pulmonary disease (COPD) and has been available since 2002. We sought to update an evaluation of the safety of tiotropium in the HandiHaler® formulation as significant clinical trial data have become available over time.MethodsPooled analysis of adverse event reporting from phase III and IV tiotropium HandiHaler® clinical trials with the following characteristics was performed: randomized, double-blind, parallel group, placebo-controlled design, tiotropium 18 μg once-daily dosing, COPD indication, duration of at least four weeks. Incidence rates by treatment group, rate differences (tiotropium–placebo), and 95% confidence intervals were determined.ResultsTwenty-six trials were identified involving 17,014 patients. Mean age was 65 years, mean forced expiratory volume in one second was 1.16 L (41% predicted), 76% men. Total exposure to study drug was 11,958 patient-years (tiotropium) and 10,578 patient-years (placebo). Tiotropium was associated with a reduced risk (expressed as rate difference [95% confidence interval] per 100 patients-years at risk) for an adverse event (−17.5 [−22.9, −12.2]), serious adverse event (−1.41 [−2.81, −0.00]) and a fatal event (−0.63 [−1.14, −0.12]). A reduced risk was present for adverse events that were cardiac (−0.79 [−1.48, −0.09]), lower respiratory (−14.2 [−17.0, −11.5]) and for a composite endpoint of major adverse cardiovascular events (−0.45 [−0.85, −0.05]). Typical expected inhaled anticholinergic effects such as dry mouth, constipation, and urinary difficulties were observed in the safety database.ConclusionThe safety data review does not indicate an increased risk for death or cardiovascular morbidity during tiotropium treatment in patients with COPD.

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“…Several countries with publicly funded general practice clinics have reoriented their remuneration systems towards a morbidity-based casemix adjustment system [ 11 ]. Denmark has yet to reorient its resource allocation system in the general practice sector towards morbidity-based casemix systems [ 12 ]. However, there seems to be a tendency or willingness to change the current system in the direction of a morbidity-based system, where a larger component is based on needs rather than the volume of visits [ 13 ].…”

Section: Context and Datamentioning

confidence: 99%

Resource allocation and the burden of co-morbidities among patients diagnosed with chronic obstructive pulmonary disease: an observational cohort study from Danish general practice

Ahnfeldt-Mollerup

Lykkegaard

Halling

et al. 2016

BMC Health Serv Res

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BackgroundChronic obstructive pulmonary disease is a leading cause of mortality, and associated with increased healthcare utilization and healthcare expenditure. In several countries, morbidity-based systems have changed the way resources are allocated in general practice. In primary care, fee-for-services tariffs are often based on political negotiation rather than costing systems. The potential for comprehensive measures of patient morbidity to explain variation in negotiated expenditures for patients with chronic obstructive pulmonary disease has not previously been examined. The aim of this study is to analyze fee-for-service expenditure of patients diagnosed with chronic obstructive pulmonary disease visiting Danish general practice clinics and further to assess what proportion of fee-for-service expenditure variation was explained by patient morbidity and general practice clinic characteristics, respectively.MethodsWe used patient morbidity characteristics such as diagnostic markers and multi-morbidity adjustment based on adjusted clinical groups (ACGs) and fee-for-service expenditure for a sample of primary care patients for the year 2010. Our sample included 3,973 patients in 59 general practices. We used a multi-level approach.ResultsThe average annual fee-for-service expenditure of caring for patients diagnosed with chronic obstructive pulmonary disease in general practice was about EUR 400 per patient. Variation in the expenditures was driven by multimorbidity characteristics up to 28 % where as characteristics such as age and gender only explained 5 %. Expenditures increased progressively with the degree of multimorbidity. In addition, expenditures were higher for patients who had diagnostic markers based on ICPC-2 (body systems and/or components such as infections and symptoms). Nevertheless, 9.8–15.4 % of the variation in expenditure was related to the clinic in which the patient was cared for.ConclusionPatient morbidity and general practice clinic characteristics are significant patient-related fee-for-service expenditure drivers in chronic obstructive pulmonary disease care.

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Comparative Safety of Long-Acting Inhaled Bronchodilators

Cited by 39 publications

References 24 publications

Long-acting Inhaled Bronchodilator and Risk of Vascular Events in Patients With Chronic Obstructive Pulmonary Disease in Taiwan Population

Long-acting Inhaled Bronchodilator and Risk of Vascular Events in Patients With Chronic Obstructive Pulmonary Disease in Taiwan Population

Tiotropium HandiHaler® in the treatment of COPD: A safety review

Resource allocation and the burden of co-morbidities among patients diagnosed with chronic obstructive pulmonary disease: an observational cohort study from Danish general practice

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Comparative Safety of Long-Acting Inhaled Bronchodilators

Cited by 39 publications

References 24 publications

Long-acting Inhaled Bronchodilator and Risk of Vascular Events in Patients With Chronic Obstructive Pulmonary Disease in Taiwan Population

Long-acting Inhaled Bronchodilator and Risk of Vascular Events in Patients With Chronic Obstructive Pulmonary Disease in Taiwan Population

Tiotropium HandiHaler&reg; in the treatment of COPD: A safety review

Resource allocation and the burden of co-morbidities among patients diagnosed with chronic obstructive pulmonary disease: an observational cohort study from Danish general practice

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Tiotropium HandiHaler® in the treatment of COPD: A safety review