Risk for death associated with medications for recently diagnosed chronic obstructive pulmonary disease

Hines Veterans Affairs Hospital, Hines, Illinois 60141, USA.
Annals of internal medicine (Impact Factor: 17.81). 09/2008; 149(6):380-90.
Source: PubMed


Concerns exist regarding increased risk for mortality associated with some chronic obstructive pulmonary disease (COPD) medications.
To examine the association between various respiratory medications and risk for death in veterans with newly diagnosed COPD.
Nested case-control study in a cohort identified between 1 October 1999 and 30 September 2003 and followed through 30 September 2004 by using National Veterans Affairs inpatient, outpatient, pharmacy, and mortality databases; Centers for Medicare & Medicaid Services databases; and National Death Index Plus data. Cause of death was ascertained for a random sample of 40% of those who died during follow-up. Case patients were categorized on the basis of all-cause, respiratory, or cardiovascular death. Mortality risk associated with medications was assessed by using conditional logistic regression adjusted for comorbid conditions, health care use, and markers of COPD severity.
U.S. Veterans Health Administration health care system.
32 130 case patients and 320 501 control participants in the all-cause mortality analysis. Of 11 897 patients with cause-of-death data, 2405 case patients had respiratory deaths and 3159 case patients had cardiovascular deaths.
All-cause mortality; respiratory and cardiovascular deaths; and exposure to COPD medications, inhaled corticosteroids, ipratropium, long-acting beta-agonists, and theophylline in the 6 months preceding death.
Adjusted odds ratios (ORs) for all-cause mortality were 0.80 (95% CI, 0.78 to 0.83) for inhaled corticosteroids, 1.11 (CI, 1.08 to 1.15) for ipratropium, 0.92 (CI, 0.88 to 0.96) for long-acting beta-agonists, and 1.05 (CI, 0.99 to 1.10) for theophylline. Ipratropium was associated with increased cardiovascular deaths (OR, 1.34 [CI, 1.22 to 1.47]), whereas inhaled corticosteroids were associated with reduced risk for cardiovascular death (OR, 0.80 [CI, 0.72 to 0.88]). Results were consistent across sensitivity analyses.
Current smoking status and lung function were not measured. Misclassification of cause-specific mortality is unknown.
The possible association between ipratropium and elevated risk for all-cause and cardiovascular death needs further study.

11 Reads
  • Source
    • "The nine on ipratropium were unusually compliant with their inhaled medication. Lee et al35 analyzed Veterans Affairs administrative databases and found an increased adjusted odds ratio of all-cause mortality of 1.11 (CI, 1.08 to 1.15) for ipratropium. Further, ipratropium exposure was associated with a 34% increase in the odds of cardiovascular death (odds ratio [OR], 1.34 [CI, 1.22 to 1.47]). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. With the significant toll of the disease, more resources have been invested in developing new treatment modalities. Among these medications, inhalational anticholinergics are widely used for the management of stable COPD. The newer agents, with longer half-lives and better safety profiles, have emerged and helped to improve management of COPD patients. The available data from randomized clinical trials support use of these agents. Multiple randomized clinical trials show safety and efficacy of the newer long-acting inhaled anticholinergics, including tiotropium and aclidinium. A recent meta-analysis of tiotropium delivered with Respimat(®) raised some safety concerns. A large trial, comparing different doses and delivery methods of inhaled tiotropium, is ongoing to determine the effect on mortality. As clinical trials may not comprehensively represent the entire COPD population, caution should be exercised when these agents are used in higher-risk populations, like individuals with cardiac arrhythmias or urinary obstruction. In this publication, we review the safety of inhalational anticholinergics.
    Drug, Healthcare and Patient Safety 03/2013; 5(1):49-55. DOI:10.2147/DHPS.S7771
  • Source
    • "The use of ICD-9 codes to identify cohorts of patient with COPD using administrative data is common [11-18]. Investigators and payers have utilized these codes to describe the epidemiology of COPD[12,14,15,17,24,34-36], to evaluate the effectiveness and safety of treatments in COPD[11,13,18,37,38], and more recently, as a means to assess the quality of care provided to patients with COPD [16]. In fact, the National Committee for Quality Assurance (NCQA) and the Agency for Health Research and Quality (AHRQ) both advocate for use of quality measures relying on ICD-9 code-based COPD case-identification [39,40]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD. Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria. 4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80). Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.
    BMC Health Services Research 02/2011; 11(1):37. DOI:10.1186/1472-6963-11-37 · 1.71 Impact Factor
  • Source
    • "Therapeutic options for patients with COPD are limited although they include LABAs and the class of inhaled anticholinergics. Both LABAs and anticholinergics decrease exacerbations; however, they have been linked to cardiovascular safety concerns.41–45 No single therapeutic agent has been conclusively shown to reduce mortality in patients with COPD in any clinical trial.11,46 "
    [Show abstract] [Hide abstract]
    ABSTRACT: The benefit harm profile of inhaled corticosteroids, and their effect on patient oriented outcomes and comorbid pneumonia, osteoporosis and cardiovascular disease in patients with chronic obstructive pulmonary disease remain uncertain. An overview of the evidence on the risks and benefits of inhaled corticosteroids (fluticasone and budesonide) in chronic obstructive pulmonary disease from recent randomized controlled trials and systematic reviews. Observational studies on adverse effects were also evaluated. Evidence from recent meta-analysis suggests a modest benefit from inhaled corticosteroid long-acting beta-agonist combination inhalers on the frequency of exacerbations, (rate ratio [RR], 0.82; 95% confidence interval [CI]: 0.78 to 0.88), in improvements in quality of life measures, and forced expiratory volume in one second when compared to long-acting beta-agonists alone. On the outcome of pneumonia, our updated meta-analysis of trials (n = 24 trials; RR, 1.56; 95% CI: 1.40-1.74, P < 0.0001) and observational studies (n = 4 studies; RR, 1.44; 95% CI: 1.20-1.75, P = 0.0001) shows a significant increase in the risk of pneumonia with the inhaled corticosteroids currently available (fluticasone and budesonide). Evidence for any intraclass differences in the risk of pneumonia between currently available formulations is inconclusive due to the absence of head to head trials. Inhaled corticosteroids have no cardiovascular effects. Among patients with chronic obstructive pulmonary disease, clinicians should carefully balance these long-term risks of inhaled corticosteroid against their symptomatic benefits.
    International Journal of COPD 08/2010; 5:189-95. · 3.14 Impact Factor
Show more

Similar Publications


11 Reads
Available from