Waikato Hospital is a major regional hospital in Hamilton, New Zealand. It provides specialised and emergency healthcare for the Midlands and Waikato area with patients referred there from feeder hospitals like Whakatāne, Lakes area, Tauranga, Thames, Tokoroa and Rotorua.
Background and objective:Recent observational data suggest that cardioselective β-blockers like bisoprolol are safe and beneficial for patients with COPD. However, the acute effects of bisoprolol on lung and cardiovascular function in these patients is unclear, a gap that this study aimed to address. Methods:This was a subanalysis of pre-randomisation screening visit data from the ongoing Preventing Adverse Cardiac Events (PACE) in COPD randomised controlled trial. If all other eligibility criteria were met, participants were orally administered an unblinded 1.25 mg tablet of bisoprolol. Post-bronchodilator spirometry, heart rate and blood pressure were monitored at 0, 30 (cardiovascular parameters only), 60 and 120 min. For this subanalysis, respiratory intolerance was defined as a decrease in forced expiratory volume in 1 s (FEV1) (L) ≥200 mL and ≥12% from the 0-min FEV1 (L) value; and cardiovascular intolerance was defined as systolic blood pressure (SBP) falling below 100 mmHg at 1 or 2 h. Results:Of 359 consented participants, 292 conducted the test-dose procedure. 13 (4.5%) were respiratory intolerant and six (2.1%) were cardiovascular intolerant at 1 or 2 h. No participant was intolerant for both. There was no significant difference in FEV1 (L) or SBP at baseline At 120 min the intolerant group's mean FEV1 had significantly decreased to 1.05 L (95% CI 0.86-1.25 L; p<0.0001); the tolerant group experienced no change (1.10, 1.05-1.14 L; p=0.33). Conclusion:The administration of 1.25 mg bisoprolol was acutely well tolerated in >95% of COPD patients.
BACKGROUND:Although cardiovascular disease is common in patients with chronic obstructive pulmonary disease (COPD), the efficacy and safety of β blockers in reducing cardiac events and mortality is uncertain. This study was designed to assess whether the cardioselective β blocker, bisoprolol, improves cardiorespiratory outcomes when added to usual COPD care. METHODS:This double-blind, randomised, controlled, phase 3 trial was done across 22 hospital and research institute sites selected by research experience and resources to conduct the study in Australia, India, New Zealand, and Sri Lanka. Participants aged 40-85 years with COPD, post-bronchodilator FEV1 30-70% predicted, and at least one COPD exacerbation in the previous 2 years were randomly assigned to receive bisoprolol (1·25-5 mg) or matched placebo, orally, once daily, for 2 years, with both groups continuing to receive usual COPD care. Randomisation was with a concealed, computer-generated sequence, stratified by site, smoking status, and previous diagnosis of cardiovascular disease requiring treatment. Participants, site personnel, and investigators remained masked to study treatment throughout the trial. The primary outcome was a composite of cardiac and respiratory effects, starting with the most important outcome (death), then cardiac or respiratory hospital admissions, exacerbations, quality-of-life measures, and FEV1. Analysis was by intention-to-treat (ITT) in all randomly assigned patients, using a country-stratified win ratio. Adverse events were analysed from the ITT population using all available data. Missing data were not used to determine wins, but regarded as a tie on that level of the hierarchy. The trial was prospectively registered on ClinicalTrials.gov (NCT03917914), Clinical Trial Registry - India (CTRI/2020/08/027322), and the Sri Lanka Clinical Trials Registry (SLCTR/2021/033). The study is complete. FINDINGS:Of 360 participants screened for eligibility between June 30, 2020, and March 20, 2023, 280 were randomly assigned to bisoprolol (n=143) or placebo (n=137), with 249 completing 2 years of follow-up. 233 patients (83%) were male and 47 (17%) were female; mean age was 68 years (SD 8). Mean post-bronchodilator FEV1 was 45% (SD 11) predicted at baseline. According to the hierarchy of outcomes, bisoprolol was associated with better cardiorespiratory health for 3041 (45%) of 6763 comparisons and placebo for 3240 (48%), with 482 (7%) showing no difference, giving a win ratio of 0·95 (95% CI 0·72 to 1·25, p=0·72) and a net benefit of -2% (95% CI -15 to 10) with bisoprolol. No significant differences were seen between bisoprolol and placebo in all-cause mortality, cardiorespiratory hospitalisations, major adverse cardiac events, or moderate or severe COPD exacerbations. Additionally, no significant differences were seen in FEV1, COPD symptoms, or quality of life, or adverse events. The most common adverse events were COPD exacerbations, occuring in 83 (58%) participants in the bisoprolol group and 87 (64%) in the placebo group. 15 (10%) participants in the bisoprolol group and 11 (8%) in the placebo group died. None of these deaths were attributed to the treatment. INTERPRETATION:In patients with moderately severe COPD, treatment with bisoprolol made no difference to overall cardiorespiratory health, all-cause mortality, or serious cardiorespiratory events. FUNDING:National Health and Medical Research Council of Australia and the Health Research Council of New Zealand.
Patients with chronic kidney disease (CKD) develop anaemia in the setting of abnormal iron metabolism and reduced endogenous erythropoietin. Pure red cell aplasia (PRCA) is a condition that, in rare cases, has been associated with erythropoietin products, commonly prescribed in patients with CKD-related anaemia. We describe 14 cases of Epoetin-alfa associated PRCA which have resulted in significant morbidity. Our cases were predominantly male (71%) with a median age of onset 68 years old. Each presented with profound anaemia 4-48 months (median 9.5 months) after commencing subcutaneous Epoetin. Heterogeneous immunosuppression regimens were used, predominantly with either monotherapy prednisone or ciclosporin. Two patients did not receive immunosuppression. Of our 14 cases, eight have since been commenced and maintained on Roxadustat with six of these subsequently reaching target haemoglobin. Of the six not commenced on Roxadustat, only one has reached target haemoglobin. This is the first multi-patient report of Roxadustat in patients with ESA-PRCA. Our cluster of cases highlights the need for strong suspicion of acquired PRCA in patients treated with erythropoietin products who present with refractory anaemia. HIF stabilisers such as Roxadustat, which have otherwise not been licensed in New Zealand, seem to be beneficial in these cases, possibly minimising the need for heavy immunosuppression.
