Long-term treatment of chronic obstructive pulmonary disease with salmeterol and the additive effect of ipratropium

The efficacy and safety of salmeterol alone was compared with the combinati on of salmeterol plus ipratropium and with placebo during long-term treatme nt in patients with stable chronic obstructive pulmonary disease, In additi on, the single-dose effect in response to the first dose of treatment was s tudied over 12 h, The patients (n=144; age 64+/-7 yrs, forced expiratory volume in one second (FEV1) 44+/-11% pred) participated in a three-centre double-blind double-p lacebo parallel group study and were randomized after a run-in period of 2 weeks to receive either salmeterol 50 mu g b.i.d., salmeterol 5 mu g b.id. plus ipratropium 40 mu g q.id. or placebo for a period of 12 weeks. The single-dose study demonstrated that salmeterol produced a significant i ncrease in FEV1 (peak of 7% pred) and specific airway conductance (sGaw) (m aximum of 60% baseline) for greater than or equal to 12 h, The combination of salmeterol plus ipratropium elicited a greater bronchodilator response ( 11% and 94% increases respectively) than salmeterol alone during the first 6 h after inhalation, During treatment there were significant improvements in daytime symptom scores and morning peak expiratory flow in both the salm eterol and the salmeterol plus ipratropium groups (p<0.001), with an associ ated decrease in the use of rescue salbutamol, Improvements in FEV1 and sGa w were greater in the salmeterol plus ipratropium group than in the patient s receiving only salmeterol, Thirty-five patients had an exacerbation; 11 ( 23%) in the salmeterol group (versus placebo NS), six (13%) in the salmeter ol plus ipratropium group (versus placebo p<0.01) and 18 (36%) in the place bo group. In conclusion, in patients with severe stable chronic obstructive pulmonary disease, long-term treatment with either salmeterol alone or salmeterol pl us ipratropium is safe and effective. There was added benefit from the comb ination therapy in terms of improvement in airways obstruction, but not for improvement in symptom control or need for rescue salbutamol.