Mortality Risk in Patients Receiving Drug Regimens with Theophylline for Chronic Obstructive Pulmonary Disease

Center for Management of Complex Chronic Care, Hines Veterans Affairs Hospital, Hines, Illinois 60141, USA.
Pharmacotherapy (Impact Factor: 2.66). 10/2009; 29(9):1039-53. DOI: 10.1592/phco.29.9.1039
Source: PubMed


To evaluate outcomes associated with six treatment regimens with theophylline versus each regimen without theophylline in patients with chronic obstructive pulmonary disease (COPD).
Retrospective cohort study.
Veterans Affairs health care system.
A total of 183,573 patients aged 45 years or older who had a diagnosis of COPD and were receiving respiratory drug therapy.
Patients' treatment regimens were identified by using data from October 1, 2002-March 31, 2003, and patients were followed for events by using data from April 1, 2003-September 30, 2005. Data from October 1, 2001-September 30, 2002, were used to define the patients' baseline characteristics. Primary outcome measures were all-cause mortality, COPD exacerbations, and COPD-related hospitalizations. Two approaches were used: first, treatment assignment was based on drug therapy at baseline, and second, exposure was measured as a time-varying covariate. Treatment groups were stratified based on propensity to receive theophylline. Mortality was compared by using Cox proportional hazards models, and other outcomes were compared with use of negative binomial models. Comparisons were conducted within individual treatment regimens that were the same with the exception of theophylline. Patients treated with ipratropium plus theophylline (largest group) compared with those treated with ipratropium alone had a 1.11-fold increase in the risk of death (95% confidence interval [CI] 1.04-1.18). For each of the other regimens, the risk of mortality associated with theophylline was greater than that in the regimens without theophylline (hazard ratios [HRs] 1.17-1.31). In the time-varying exposure analysis, theophylline (HR 1.23, 95% CI 1.09-1.39) was associated with an increased mortality risk.
Patients receiving regimens that included theophylline had slightly increased risks of mortality, COPD exacerbations, and COPD hospitalizations compared with patients receiving the same regimens without theophylline. However, the benefits of theophylline on other factors, including symptoms, quality of life, and activities of daily living, were not measured. Clinicians should consider all of the potential benefits and harms associated with theophylline when making treatment recommendations.

19 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: agents administered during hospi- talization at a tertiary care acade- mic medical center. The retrospec- tive analysis was conducted over 1 year. A total of 416 allergies were reported among 300 patients; more than 1 allergy was reported by more than one-fourth of study patients (82/300 (27.3%)). Only 36.3% (151/416) of allergies reported were accompanied by a reaction description (95% confi- dence interval (CI), 31.7% to
    Preview · Article ·
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: MEDICATION SAFETY Overlooked Renal Dosage Adjustments A retrospective analysis of 647 patients at hospital discharge com-pared required renal dosage adjust-ments to dosage actually prescribed. This study was conducted at VieCuri Medical Centre in Venlo, Netherlands. Patient demographics and renal function data were col-lected, and dosage adjustment needs were assessed via the pharmacy-supported discharge counseling ser-vice. The incidence of inappropriate dosing based on renal function was measured at hospital discharge. Thirty-seven percent of patients evaluated during the study period (237/647) had a creatinine clear-ance less than 51 mL/min/1.73 m 2 ; dosage adjustment was warranted in 23.9% (411/1,718) of prescrip-tions. When dosage adjustment should have been performed, more than 40% of prescriptions (169/411; 41.1%) were inappropri-ate for renal function (9.8% of pre-scriptions overall; 169/1,718). Fur-thermore, 60.4% (102/169) of inappropriate prescriptions pos-sessed the potential for moderate or severe clinical consequences, as evaluated by a panel of two clinical pharmacologists and one nephrolo-gist. Study authors also noted a lack of standardized dosing guidelines for agents requiring renal dosage adjustment. The authors also sug-gested that augmenting medication systems by adding dynamic renal dosing alerts would improve moni-toring. Summary: A comparison of suggested renal dosing and actual dosing at hospital discharge revealed that appropriate prescribing may be overlooked. van Dijk EA, Drabbe NRG, Kruijtbosch M, De Smet PAGM. Drug dosage adjust-ments according to renal function at hos-pital discharge. Ann Pharmacother. 2006;40:1254-1260.
    Preview · Article · Dec 1122 · Hospital pharmacy
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although the main characteristic of chronic obstructive pulmonary disease (COPD) is relentlessly worsening airflow limitation, many patients show some degree of reversibility and, more importantly, clinically relevant improvements in dyspnea, exercise capacity, and health status following the administration of a bronchodilator. The mechanism through which bronchodilators effect these improvements appears to be a reduction in hyperinflation both at rest and during exercise. Bronchodilators also consistently reduce exacerbations. As a result, bronchodilators have become the recommended cornerstone of maintenance treatment of COPD. Three classes of bronchodilators are currently available: the oral methylxanthine theophylline, both short-acting (SA) and long-acting (LA) inhaled b 2 -adrenergic receptor agonists (BA), and anticholinergics (AC) or muscarinic receptor antagonists (MA). The SA inhaled bronchodilators are still used for rescue treatment, but should, for maintenance treatment, be replaced by their LA counterparts for reasons of both efficacy and convenience. Evidence also advocates the introduction of LA inhaled bronchodilators early in the disease process. Among the available LA inhaled bronchodilators, the once daily LAMA tiotropium appears a safe, effective, and convenient choice to initiate maintenance treatment with, but the advent of equally effective and convenient once daily LABAs and LAMAs may offer clinicians a valid alternative. Furthering the debate as to which bronchodilator to start maintenance treatment with is somewhat superfluous, as the constant finding that a combination of bronchodilators acting through different mechanisms has at numerous times been shown to be superior and perhaps safer than treatments with a single bronchodilator class. Once-daily combinations of LAMA and LABA formulated into one single device are now under way and probably will become the preferred maintenance treatment for COPD patients. Finally, another important step forward in the treatment of COPD will be the development of inhalation devices delivering aerosols with optimal pulmonary deposition and equipped with features that facilitate their correct handling by the COPD patient.
    Preview · Article · Nov 2009 · Annals of Respiratory Medicine
Show more