Background The findings of the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) study may be poorly generalisable to tiotropium use in clinical practice.
Methods An audit of 226 patients admitted to Wellington Hospital with a chronic obstructive pulmonary disease exacerbation determined the proportion of patients prescribed tiotropium on discharge that would have been ineligible for inclusion in the UPLIFT study.
Results Among 100 patients prescribed tiotropium, 38/100; 38% (95% CI 28.5% to 48.3%) would have been ineligible for UPLIFT at the time of the hospital discharge due to recent cardiovascular comorbidity or moderate to severe renal impairment.
Conclusions The UPLIFT findings have limited generalisability to over a third of patients prescribed tiotropium following a hospital admission with a chronic obstructive pulmonary disease exacerbation in New Zealand.
- COPD Pharmacology
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The initial clinical research programme of the inhaled anticholinergic agents ipratropium bromide and tiotropium in chronic obstructive pulmonary disease (COPD) suggested their use may increase the risk of serious cardiovascular events and mortality.1 ,2 These concerns were allayed with publication of the large, postregistration study Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) which reported no increased risk of mortality or myocardial infarction with tiotropium HandiHaler.3 However, the UPLIFT findings may be poorly generalisable to patients with COPD, due to the exclusion of potential research participants with recent cardiac comorbidity or renal impairment.2 ,3
To determine the generalisability of the UPLIFT findings, we undertook an audit of patients admitted to hospital with an exacerbation of COPD. Discharge coding was used to search for all non-elective admissions to Wellington Hospital with a primary diagnostic code of COPD (International Classification of Diseases, 10th Revision code J44.x). Admissions were examined in chronological order from 1 January 2011 until 100 patients prescribed tiotropium on discharge were included. If a patient had multiple admissions, the first admission with COPD was examined. In New Zealand tiotropium is only available in the HandiHaler 18 µg per actuation preparation.
Data were collected from electronic records, including: tiotropium prescribing, cardiovascular comorbidities, renal function and medications. Comorbidities were further categorised by the cardiovascular and renal exclusion criteria used in postregistration tiotropium HandiHaler studies including the UPLIFT trial:
cardiac arrhythmias that were deemed unstable or life-threatening, or required intervention or change in drug therapy within the last year
myocardial infarction that occurred within the last 6 months
heart failure (New York Heart Association Class III or IV) that required hospital inpatient management within the last year
moderate to severe renal impairment, which for the audit was defined as a discharge estimated glomerular filtration rate <60 ml/min/1.73 m2
There were 247 admissions between 1 January 2011 and 31 August 2011. There were 21 patients excluded because either they did not survive the admission, the discharge diagnosis was not COPD or there were inadequate discharge notes.
There were 100 patients prescribed tiotropium on discharge, of whom 14, 14% (95% CI 7.9% to 22.4%) were also prescribed ipratropium bromide. Of patients prescribed tiotropium on discharge, 38/100, 38% (95% CI 28.5% to 48.3%) would have been ineligible for inclusion in the UPLIFT study because of recent cardiovascular or renal comorbidity (table 1). There were 10/100 patients in whom tiotropium was started during the index hospital admission; 5 of these patients would have been ineligible for inclusion in UPLIFT. Information on eligibility at the time of first tiotropium prescription was not available for the 90 patients prescribed tiotropium prior to hospital admission. The incidence of comorbidities was similar in patients not prescribed tiotropium, reflecting the common occurrence of cardiovascular and renal comorbidities in patients admitted with an exacerbation of COPD, and suggesting their presence did not influence its prescription.
In summary, 38% of patients prescribed tiotropium would not have been eligible for inclusion in the UPLIFT study at the time of hospital discharge due to recent cardiovascular or renal comorbidity. The tiotropium HandiHaler datasheet does not give details of the limited evidence-base for tiotropium HandiHaler in patients with COPD with these comorbidities4 and this is likely to underlie the observed prescription patterns.
We conclude that the UPLIFT findings have limited generalisability to over a third of patients prescribed tiotropium following a hospital admission with a COPD exacerbation in New Zealand.
Contributors SW and JF undertook the data collection which was analysed by MW. All authors contributed to the drafting of the manuscript.
Competing interests RB has been a member of the GlaxoSmithKline (NZ) advisory board, consulted for Cytos Biotechnology and Pharmaxis, received research grants from AstraZeneca, Cephalon, Chiesi, Genentech, GlaxoSmithKline and Novartis, and payment for lectures or support to attend meetings from Boehringer Ingelheim, GlaxoSmithKline, Novartis, Nycomed and Otsuka Pharmaceuticals. JF has received payment for lectures or support to attend meetings from AstraZeneca, Boehringer Ingelheim and Novartis. SW and MW have no competing interests to declare.
Ethics approval Ethical approval was obtained from the Central Regional Ethics Committee [12/CEN/16].
Provenance and peer review Not commissioned; internally peer reviewed.