Primary Care COPD Patients Compared with Large Pharmaceutically-Sponsored COPD Studies : An UNLOCK Validation Study
TL;DR: Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations, as hitherto unknown GOLD I exacerbation characteristics are revealed.
Abstract: Background: Guideline recommendations for chronic obstructive pulmonary disease (COPD) are based on the results of large pharmaceutically-sponsored COPD studies (LPCS). There is a paucity of data on disease characteristics at the primary care level, while the majority of COPD patients are treated in primary care. Objective: We aimed to evaluate the external validity of six LPCS (ISOLDE, TRISTAN, TORCH, UPLIFT, ECLIPSE, POET-COPD) on which current guidelines are based, in relation to primary care COPD patients, in order to inform future clinical practice guidelines and trials. Methods: Baseline data of seven primary care databases (n = 3508) from Europe were compared to baseline data of the LPCS. In addition, we examined the proportion of primary care patients eligible to participate in the LPCS, based on inclusion criteria. Results: Overall, patients included in the LPCS were younger (mean difference (MD)-2.4; p = 0.03), predominantly male (MD 12.4; p = 0.1) with worse lung function (FEV1% MD -16.4; p = 1 and >= 2 exacerbations, although results were not statistically significant. Our findings add to the literature, as we revealed hitherto unknown GOLD I exacerbation characteristics, showing 34% of mild patients had >= 1 exacerbations per year and 12% had >= 2 exacerbations per year. The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT). Conclusion: Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations. More research is needed to determine the effect of pharmacological treatment in mild to moderate patients. We encourage future guideline makers to involve primary care populations in their recommendations.
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TL;DR: Tiotropium Respimat and HandiHaler have similar safety and efficacy profiles in patients who are naive to anticholinergic therapy.
Abstract: Patients with chronic obstructive pulmonary disease (COPD) who were naive to anticholinergics before the TIOtropium Safety and Performance In Respimat (TIOSPIR) trial may reflect patients seen in practice, in particular in primary care. In addition, investigating safety in these patients avoids the potential bias in patients who previously received anticholinergics and may be tolerant of their effects. The aim of this study was to evaluate whether patients naive to anticholinergic therapy who were treated with tiotropium Respimat 2.5 or 5 μg had different safety and efficacy outcomes than patients treated with tiotropium HandiHaler 18 μg. A post hoc analysis of patients who were not receiving anticholinergics before TIOSPIR (N=6,966/17,135) was conducted. Primary end points were risk of death from any cause and risk of COPD exacerbation. Secondary outcomes included severe exacerbation and major adverse cardiovascular events (MACE). Additional analysis of exacerbations was carried out in anticholinergic-naive patients with moderate (GOLD II) disease. Anticholinergic-naive patients had less severe disease than the total TIOSPIR population. Discontinuations because of anticholinergic side effects were infrequent (0.9% overall). Similar to the primary study, patients in the tiotropium Respimat groups had no difference in the risk of death or risk of any or severe exacerbation than patients treated with tiotropium HandiHaler. Risk of MACE was similar across the Respimat and HandiHaler groups. Rates of exacerbations in the subgroup of patients with moderate disease were similar across the Respimat and HandiHaler groups. Tiotropium Respimat and HandiHaler have similar safety and efficacy profiles in patients who are naive to anticholinergic therapy. Inhaled forms of the drug tiotropium are safe and effective for patients with chronic lung disease. Breathing difficulties caused by chronic obstructive pulmonary disease (COPD) can be treated using the 'anticholinergic' drug tiotropium, which works by enlarging the patient's airways. Tiotropium is available as a dry powder or aqueous solution inhaler. The inhaler was recently confirmed as safe in randomized trials, however, there were concerns that the trials did not verify safety and efficacy for patients new to anticholinergic therapy. Robert Wise at Johns Hopkins University School of Medicine in Baltimore, USA, and co-workers tested two inhaled forms of tiotropium on 6,966 COPD patients new to anticholinergics. Their results indicated both inhalers were effective and presented low risks of death, heart problems or other side effects, regardless of previous exposure to anticholinergics.
16 citations
TL;DR: A unique patient-level simulation model is developed that can be used to evaluate COPD treatment options for a variety of subgroups and results for a selection of treatment scenarios and subgroups were shown to demonstrate the potential of the model.
16 citations
TL;DR: The intervention introduced a COPD care bundle and aimed at enhancing collaboration between GPs and practice assistants and was associated with significantly higher implementation rates in seven out of nine key elements of care.
Abstract: Disease management of chronic obstructive pulmonary disease (COPD) is complex and shortcomings in general practice care for COPD are common. A care bundle is a disease management aid used as a reminder and for steering specific elements of care. Our objectives were to test whether a COPD care bundle delivered to general practitioners (GPs) and practice assistants increases the implementation of key elements of COPD care.The study was a cluster-randomised clinical trial, with 1:1 randomisation of GPs and a 1-year follow-up. The intervention introduced a COPD care bundle and aimed at enhancing collaboration between GPs and practice assistants. The control group continued usual care. The primary outcome measure was the composite score from nine key elements of COPD care measured at the patient level.We enrolled 35 GPs and 216 patients with a median age of 69 years, 59% female, 69% Global Initiative for Chronic Obstructive Lung Disease group A or B. After 1 year, the between-group difference in change of the primary outcome measure was +2.2 (95% CI +1.5- +2.9) in favour of the intervention group. The intervention was associated with significantly higher implementation rates in seven out of nine key elements of care.Disease management using a COPD care bundle increased the implementation of key elements of COPD care in general practice.
16 citations
TL;DR: Although there were gender differences in baseline characteristics, IND/GLY demonstrated similar trends for exacerbation prevention and lung function improvement in men and women with moderate-to-very-severe COPD and a history of exacerbations compared with SFC.
Abstract: The burden of chronic obstructive lung disease (COPD) is increasing in women, with recent evidence suggesting gender differences in disease characteristics and potentially in treatment outcomes. FLAME was a 52-week randomized controlled trial in patients with severe-to-very-severe COPD and a history of exacerbations. In this post-hoc analysis, gender-based baseline differences and treatment outcomes between indacaterol/glycopyrronium 110/50 μg once daily (IND/GLY) and salmeterol/fluticasone 50/500 twice daily (SFC) were assessed in terms of rate of exacerbations, time-to-first exacerbation, lung function, health status, and rescue medication use. This post-hoc analysis included 2557 men and 805 women. Baseline characteristics differed between genders, with women being younger, having better lung function and more often experiencing ≥2 exacerbations in the previous year. Compared with SFC, IND/GLY treatment was associated with reductions in the annualized rates of moderate/severe exacerbations (rate ratio [95% CI]: 0.81 [0.73–0.91], 0.89 [0.74–1.07] in men and women, respectively). Similarly, time-to-first moderate/severe exacerbation was also delayed (hazard ratio [95% CI]: 0.79 [0.70–0.89] and 0.76 [0.63–0.91] in men and women, respectively). Results were similar for all (mild/moderate/severe) exacerbations. Improvements in lung function, health status and rescue medication use with IND/GLY vs SFC were comparable between men and women. The smaller sample size for women may account for some observed discrepancies in treatment responses. Although there were gender differences in baseline characteristics, IND/GLY demonstrated similar trends for exacerbation prevention and lung function improvement in men and women with moderate-to-very-severe COPD and a history of exacerbations compared with SFC. Small differences in the effects seen between genders may be attributed to the different sizes of the two groups and need to be further evaluated in randomized trials that are appropriately powered for gender analysis. Post hoc analysis of the FLAME study. ClinicalTrials.gov
number: NCT01782326
. Registered 1 February 2013.
16 citations
Cites background from "Primary Care COPD Patients Compared..."
...Historically, many more men than women participate in randomized clinical trials in COPD, and the increasing prevalence of COPD in women is only slowly being reflected in trial populations, in contrast to real life [12]....
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TL;DR: Patients who experienced a greater exacerbation burden after initiation of maintenance therapy had worse lung function at diagnosis and a more rapid lung function decline thereafter, which emphasizes the need for better treatment strategies.
Abstract: Introduction Early identification of preventable risk factors of COPD progression is important. Whether exacerbations have a negative impact on disease progression is largely unknown. We investigated whether the long-term occurrence of exacerbations is associated with lung function decline at early stages of COPD. Methods Patients diagnosed with mild/moderate COPD (obstruction and FEV1% predicted 50-90%), aged ≥35 years, and a smoking history, who had ≥6 years of UK electronic medical records after initiation of maintenance therapy were studied. Multilevel mixed-effect linear regression was performed to determine the association between the count of any year in which the patient had ≥1 exacerbation over a 6-year period and FEV1 decline, adjusted for sex, age, anthropometrics and smoking habits. Exacerbations were defined as any prescription for an acute oral corticosteroid course and/or lower respiratory-related antibiotics and/or any COPD-related emergency or inpatient hospitalization. Results Of 11,337 patients included (mean age 65 years; 49% female) 31.6%, 23.3%, 16.6%, 11.6%, 8.1%, 5.3% and 3.4% had 0, 1, 2, 3, 4, 5 and 6 years with ≥1 exacerbation. The mean annual FEV1 decline accelerated by 1.50 mL/year (95% Confidence Interval 1.02; 1.98) with every additional year with ≥1 exacerbation from 31.0 mL/year in subjects without any exacerbation to 40.0 mL/year in patients experiencing ≥1 exacerbation every year. Patients with more years with ≥1 exacerbation had a lower mean FEV1 at first diagnosis: 14.7 mL (11.7; 17.8) lower with every additional year with exacerbations. When counting years with ≥2 exacerbations, greater effects were observed (2.19 [1.50; 2.88] mL/year excess decline per year with ≥2 exacerbations; 16.5 mL [12.1; 20.8] lower FEV1 at diagnosis). Conclusion Patients who experienced a greater exacerbation burden after initiation of maintenance therapy had worse lung function at diagnosis and a more rapid lung function decline thereafter, which emphasizes the need for better treatment strategies.
15 citations
References
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University of Manchester1, University of Barcelona2, St George's Hospital3, University of Marburg4, University of Texas Health Science Center at San Antonio5, Imperial College London6, University of Modena and Reggio Emilia7, University of Michigan8, Hokkaido University9, University of British Columbia10
TL;DR: It is recommended that spirometry is required for the clinical diagnosis of COPD to avoid misdiagnosis and to ensure proper evaluation of severity of airflow limitation.
Abstract: Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.
17,023 citations
TL;DR: Representatives from many countries serve as a network for the dissemination and implementation of programs for diagnosis, management, and prevention of COPD.
Abstract: Representatives from many countries serve as a network for the dissemination and implementation of programs for diagnosis, management, and prevention of COPD. The GOLD Board of Directors is grateful to the many GOLD National Leaders who participated in discussions of concepts that appear in GOLD reports.
3,165 citations
TL;DR: The reduction in death from all causes among patients with COPD in the combination-therapy group did not reach the predetermined level of statistical significance, and there were significant benefits in all other outcomes among these patients.
Abstract: We conducted a randomized, double-blind trial comparing salmeterol at a dose of 50 μg plus fluticasone propionate at a dose of 500 μg twice daily (combination regimen), administered with a single inhaler, with placebo, salmeterol alone, or fluticasone propionate alone for a period of 3 years. The primary outcome was death from any cause for the comparison between the combination regimen and placebo; the frequency of exacerbations, health status, and spirometric values were also assessed. Results Of 6112 patients in the efficacy population, 875 died within 3 years after the start of the study treatment. All-cause mortality rates were 12.6% in the combinationtherapy group, 15.2% in the placebo group, 13.5% in the salmeterol group, and 16.0% in the fluticasone group. The hazard ratio for death in the combination-therapy group, as compared with the placebo group, was 0.825 (95% confidence interval [CI], 0.681 to 1.002; P = 0.052, adjusted for the interim analyses), corresponding to a difference of 2.6 percentage points or a reduction in the risk of death of 17.5%. The mortality rate for salmeterol alone or fluticasone propionate alone did not differ significantly from that for placebo. As compared with placebo, the combination regimen reduced the annual rate of exacerbations from 1.13 to 0.85 and improved health status and spirometric values (P<0.001 for all comparisons with placebo). There was no difference in the incidence of ocular or bone side effects. The probability of having pneumonia reported as an adverse event was higher among patients receiving medications containing fluticasone propionate (19.6% in the combination-therapy group and 18.3% in the fluticasone group) than in the placebo group (12.3%, P<0.001 for comparisons between these treatments and placebo). Conclusions The reduction in death from all causes among patients with COPD in the combinationtherapy group did not reach the predetermined level of statistical significance. There were significant benefits in all other outcomes among these patients. (ClinicalTrials.gov number, NCT00268216.)
3,037 citations
TL;DR: The St George's Respiratory Questionnaire is a standardized self-completed questionnaire for measuring impaired health and perceived well-being in airways disease and the background and rationale for its development are discussed together with an analysis of its performance.
2,621 citations
"Primary Care COPD Patients Compared..." refers methods in this paper
...We used the St Georges Respiratory Questionnaire (SGRQ) which is designed to measure health- related quality of life in patients with asthma and COPD [34]....
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TL;DR: Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype, which has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity.
Abstract: BACKGROUND: Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. METHODS: We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. RESULTS: Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. CONCLUSIONS: Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
2,459 citations
"Primary Care COPD Patients Compared..." refers background in this paper
...Selection for large COPD studies The proportion of patients from primary care that would be eligible to be included in the LPCS ranged from 17% (TRISTAN trial) to 42% (ECLIPSE and UPLIFT study) (Table 7)....
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...In addition to five large trials, we decided to include the ECLIPSE cohort study as well, because this is an important observational study often cited in guidelines, especially with regard to exacerbation frequency patterns....
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...Exacerbation data Individual datasets: UNLOCK studies reporting exacerbation data were compared with baseline data of the ISOLDE, TRISTAN, TORCH, UPLIFT and ECLIPSE studies (Table 3)....
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...The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT)....
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...Overall mean MRC scores were similar in the UNLOCK studies compared to ECLIPSE: 2.1 (0.8) and 2.7 (1.1), respectively....
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