title: Incidence, Predictors, and Clinical Implications of Discontinuing Therapy with Inhaled Long-Acting Bronchodilators among Patients with Chronic Obstructive Pulmonary Disease.
abstract: Incidence, predictors and effect of discontinuation of long-acting bronchodilators on the risk of death or hospital admission among adults with Chronic Obstructive Pulmonary Disease (COPD) were assessed in a large population-based prospective study carried out by linking Italian healthcare utilization databases. Specifically, the cohort of 17,490 beneficiaries of the National Health Service in the Italian Region of Lombardy, aged 40 years or older, who started long-acting bronchodilators therapy during 2005-2008 was followed from first dispensation until 2012. During this period, patients who experienced discontinuation of long-acting bronchodilators were identified. Hospitalizations for COPD and deaths for any cause (composite clinical outcome) were also identified during follow-up. A Cox proportional hazards model was fitted to identify predictors of discontinuation. The case-crossover design was used to assess the implications of treatment discontinuation on the clinical outcome risk. Cumulative incidences of discontinuation were, respectively, 67%, 80%, and 92% at 6 months, 1 year, and 5 years since initial treatment. Significant predictors of discontinuation were female gender, younger age, starting treatment with fixed-dose combination of inhaled bronchodilators and corticosteroids, using antibiotics, inhaled long-acting bronchodilators and corticosteroids and not using short-acting bronchodilators, other respiratory drugs and systemic corticosteroids during follow-up. Odds ratios (95% confidence intervals) for the clinical outcome associated with not discontinuing long-acting bronchodilators was 0.64 (0.50 to 0.82). In conclusion, in the real-life setting, discontinuation of inhaled long-acting bronchodilators in adults with COPD is high even after just 6 months, even though persistence to these drugs reduces the risk of severe outcomes.
authors.affiliation: a Laboratory of Healthcare Research and Pharmacoepidemiology , Unit of Biostatistics , Epidemiology, and Public Health , Department of Statistics and Quantitative Methods , University of Milano-Bicocca , Milan , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Arfè
authors.affiliation: a Laboratory of Healthcare Research and Pharmacoepidemiology , Unit of Biostatistics , Epidemiology, and Public Health , Department of Statistics and Quantitative Methods , University of Milano-Bicocca , Milan , Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Nicotra
authors.affiliation: b Institute of Respiratory Diseases , University of Sassari , Sassari , Italy.
authors.forename: Isa
authors.initials: I
authors.lastname: Cerveri
authors.affiliation: c Unit of Epidemiology and Medical Statistics , University of Verona , Verona , Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: de Marco
authors.affiliation: d Division of Pneumology , "Guido Salvini" Hospital , Garbagnate Milanese , Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Vaghi
authors.affiliation: e Operative Unit of Territorial Health Services , Region Lombardia , Milan , Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Merlino
authors.affiliation: a Laboratory of Healthcare Research and Pharmacoepidemiology , Unit of Biostatistics , Epidemiology, and Public Health , Department of Statistics and Quantitative Methods , University of Milano-Bicocca , Milan , Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corrao
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008498:Medical Record Linkage; D008875:Middle Aged; D009026:Mortality; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality*; D012307:Risk Factors; D012737:Sex Factors; D028761:Withholding Treatment
chemical_list: D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents; D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations
keywords: Chronic obstructive pulmonary disease; death; discontinuation; healthcare utilization database; hospital admission; long-acting bronchodilators; persistence