• COPD Pharmacology

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.