Abstract

We investigated if serial domiciliary measures of spirometry were sensitive at detecting subtle effects of beta-2 blockade associated with bisoprolol. This was a sub-study of NCT01656005 where domiciliary diary data were available on n=17 patients with GOLD B/C COPD comprising domiciliary FEV₁,(am/pm), heart rate, oxygen saturation, salbutamol use, and global symptom score. Patients received a two week run in (baseline) on inhaled corticosteroid (ICS) and long acting beta-2 agonist (LABA): beclometasone/formoterol 100/6 µg, 2 puffs BID. Thereafter they were placed on triple therapy with the addition of a long acting muscarinic receptor antagonist (LAMA) as Tiotropium 18 µg OD, with concomitant weekly dose titration of bisoprolol as: 1.25 mg-2.5 mg-5 mg. After a further week of bisoprolol 5 mg, they were stepped back down to dual therapy (ICS/LABA) and continued this for one week. Mean age was 64 years, mean FEV₁52% predicted, mean FEV₁/FVC ratio of 0.46, mean 50 pack year smoking history, and 7% mean FEV₁ reversibility to salbutamol 400 µg. Compared to a baseline am FEV₁ of 1.38 L (95% CI 1.14–1.61 L), both ICS/LABA/LAMA and ICS/LABA in conjunction with bisoprolol showed statistically significant mean falls in amounting to 100 ml 1.28 L (95% CI 1.03–1.53 L) and 120 ml respectively 1.26 L (95% CI 1.01–1.51 L); equalling and exceeding the MCID of 100 ml respectively. Bisoprolol produced a significant heart reduction of 11 beats/min from a baseline of 80 bpm (95% CI 74–85 bpm) to 69 bpm (95% CI 64–73 bpm) and 69 bpm (95% CI 65–73 bpm) for ICS/LABA/LAMA and ICS/LABA respectively. There was no change in salbutamol use, symptom score or oxygen saturation, pre and post bisoprolol, irrespective of triple or dual therapy. In the context of dual or triple therapy , bisoprolol was associated with subtle but significant falls in domiciliary FEV₁, which were disconnected from symptoms, reliever use and oxygen saturation.