Hospitalizations and Mortality in the Lung Health Study

Anthonisen, Nicholas R.; Connett, John E.; Enright, Paul; Manfreda, Jure

doi:10.1164/rccm.2110093

Cited by 515 publications

(390 citation statements)

References 10 publications

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“…Biological plausibility is also suggested by the observation that ipratropium bromide increases cardiovascular risk, thereby suggesting that the increase in risk may represent a class effect of inhaled anticholinergic agents. This was originally observed in the Lung Health Survey, in which the regular use of ipratropium bromide by metered dose inhaler increased the risk of cardiovascular death, RR 2.57 (95% CI 1.12-6.62) [36]. Ipratropium bromide was also noted to increase the risk of hospital admission due to arrhythmias with a relatively high prevalence of supraventricular tachycardia.…”

Section: Biological Plausibilitymentioning

confidence: 73%

Tiotropium Respimat increases the risk of mortality: pro

Beasley

2013

Eur Respir J

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@ERSpublications Tiotropium Respimat increases mortality risk. First do no harm. Tiotropium Respimat should not be prescribed in COPD http://ow.ly/mzPGL Systematic reviews and meta-analyses of randomised controlled trials of medications provide a high standard of evidence to inform clinical practice, and can be considered the ''gold standard'' for assessing the risk/benefit profile of treatments [1,2]. Three systematic reviews and meta-analyses (including a Cochrane Review) of randomised placebo-controlled trials of tiotropium Respimat, each using different methods, have demonstrated a 50% increased risk of mortality, with its use in patients with chronic obstructive pulmonary disease (COPD) [3][4][5]. These analyses provide substantive evidence that tiotropium Respimat increases mortality in the treatment of COPD [6,7]. It is informative to review each of the systematic reviews and the issues that have been raised relevant to their interpretation.In 2011 the British Medical Journal (BMJ) published the first systematic review and meta-analysis, which included all parallel-group, randomised, placebo-controlled trials of tiotropium Respimat in the treatment of COPD that had reported data on mortality and were of a minimum 30-day duration [3] (table 1 [ [8][9][10]). Five trials were included in the analysis, two 12-week trials and three 12-month trials, studying 6522 participants. All five trials were judged to be at low risk of bias. Tiotropium Respimat significantly increased the risk of all-cause mortality, relative risk 1.52 (95% CI 1.06-2.16). There was an apparent dose-response effect on all-cause mortality, with RR 1.46 (95% CI 1.01-2.10) and 2.15 (95% CI 1.03-4.51), for the 5-mg and 10-mg preparations, respectively ( fig. 1). The overall estimates were not substantially changed by sensitivity analyses using the random effects model, limiting the analysis to three trials of 1-year duration period each, or the inclusion of additional preliminary data on tiotropium Respimat from an unpublished study. An accompanying editorial calculated, based on these figures, that one excess death is expected for every 121 (COPD) patients treated with a 5 mg dose of tiotropium by Respimat for 12 months [11].The 2012 Cochrane Review of tiotropium included the same five randomised placebo-controlled clinical trials of tiotropium Respimat, but used the Peto method for pooled estimation of odds ratio, which is arguably more appropriate for the combined analysis of rare events such as death [4]. Tiotropium Respimat significantly increased the risk of mortality, OR 1.47 (95% CI 1.04-2.08). In contrast there was no increased risk of mortality with tiotropium HandiHaler, OR 0.92 (95% CI 0.80-1.05).In 2012 Thorax published a systematic review with direct comparison and mixed treatment comparison meta-analyses of randomised controlled trials of medications used in the treatment of COPD that provided data about overall or cardiovascular death, and were a minimum 6 months in trial duration [5]. In the direct comparison meta-analysis, ti...

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Section: Biological Plausibilitymentioning

confidence: 73%

Tiotropium Respimat increases the risk of mortality: pro

Beasley

2013

Eur Respir J

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“…5,8,11,24 The relatively low mortality rate is likely due to the fact that patients were recruited from outpatient clinics, not from hospitals settings 25 where mortality rates can be up to 49% at 2 years. 26 FEV 1% had the strongest association with mortality in our study, a relationship that has been observed in other studies.…”

Section: Discussionmentioning

confidence: 99%

Predictors of Mortality in Patients with Stable COPD

et al. 2008

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OBJECTIVES:To determine which easily available clinical factors are associated with mortality in patients with stable COPD and if health-related quality of life (HRQoL) provides additional information. DESIGN:Five-year prospective cohort study. SETTING:Five outpatient clinics of a teaching hospital.PARTICIPANTS: Six hundred stable COPD patients recruited consecutively. MEASUREMENTS:The variables were age, FEV 1% , dyspnea, previous hospital admissions and emergency department visits for COPD, pack-years of smoking, comorbidities, body mass index, and HRQoL measured by Saint George's Respiratory Questionnaire (SGRQ), Chronic Respiratory Questionnaire (CRQ), and ShortForm 36 (SF-36). Logistic and Cox regression models were used to assess the influence of these variables on mortality and survival.RESULTS: FEV 1% (OR: 0.62, 95% CI 0.5 to 0.75), dyspnea (OR 1.92, 95% CI 1.2 to 3), age (OR 2.41, 95% CI 1.6 to 3.6), previous hospitalization due to COPD exacerbations (OR 1.53, 1.2 to 2) and lifetime pack-years (OR 1.15, 95% CI 1.1 to 1.2) were independently related to respiratory mortality. Similarly, these factors were independently related to all-cause mortality with dyspnea having the strongest association (OR 1.54, 95% CI 1.1 to 2.2). HRQoL was an independent predictor of respiratory and all-cause mortality only when dyspnea was excluded from the models, except scores on the SGRQ were associated with all-cause mortality with dyspnea in the model. CONCLUSIONS:Among patients with stable COPD, FEV 1% was the main predictor of respiratory mortality and dyspnea of all-cause mortality. In general, HRQoL was not related to mortality when dyspnea was taken into account, and CRQ and SGRQ behaved in similar ways regarding mortality.KEY WORDS: chronic obstructive pulmonary disease; mortality; healthrelated quality of life.

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“…It is well known that most COPD patients die from causes other than COPD. In mild COPD in the Lung Health Study [7], the largest single cause was actually lung cancer. In the present study, death from ischaemic heart disease was more frequent; however, among subjects with COPD, death from lung cancer made up 10% of all deaths.…”

Section: Discussionmentioning

confidence: 99%

“…From the American National Health and Nutrition Examination Survey (NHANES), it seems that not only mild but also moderate and severe stages of COPD are underdiagnosed [3]. There are few data available concerning underestimation of COPD as cause of death; in fact, only relatively few studies have focused on causes of death in COPD [4][5][6][7][8] and several of them have selected populations. Very little is known about the validity of mortality statistics in COPD.…”

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confidence: 99%

Potential misclassification of causes of death from COPD

Høgh‐Jensen

Godtfredsen²,

Lange³

et al. 2006

Eur Respir J

136

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Little is known about causes of death in chronic obstructive pulmonary disease (COPD) and the validity of mortality statistics in COPD. The present authors examined causes of death using data from the Copenhagen City Heart Study.Of the 12,979 subjects with sufficient data from the baseline examination during [1976][1977][1978]6,709 died before 2001. Of these, 242 died with COPD as cause of death. Among subjects with at least severe COPD at baseline, only 24.9% had COPD as cause of death and, in almost half of the cases where COPD was listed as cause of death, the subject had a normal forced expiratory volume in one second /forced vital capacity ratio at baseline.In COPD patients, having COPD on the death certificate was associated with chronic mucus hypersecretion (CMH) at baseline, an odds ratio (OR) of 3.6 (95% confidence interval 1.7-7.7), and being female (OR 2.7 (1.3-5.6)). In subjects without COPD, CMH and smoking were predictors of COPD as underlying cause of death, ORs 2.3 (1.5-3.7) and 2.2 (1.4-3.6), respectively.It was concluded that chronic obstructive pulmonary disease is underreported on death certificates, that biases in the use of chronic obstructive pulmonary disease as cause of death can be assessed, and that possible ''over-diagnosis'' of chronic obstructive pulmonary disease on death certificates in subjects unlikely to have significant disease should initiate caution when using causes of mortality in chronic obstructive pulmonary disease epidemiology.

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Hospitalizations and Mortality in the Lung Health Study

Cited by 515 publications

References 10 publications

Tiotropium Respimat increases the risk of mortality: pro

Tiotropium Respimat increases the risk of mortality: pro

Predictors of Mortality in Patients with Stable COPD

Potential misclassification of causes of death from COPD

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