Inhaled formoterol dry powder versus ipratropium bromide in chronic obstructive pulmonary disease. Efficacy of salmeterol xinafoate in the treatment of COPD. Use of a long-acting inhaled beta2-adrenergic agonist, salmeterol xinafoate, in patients with chronic obstructive pulmonary disease. Long-term treatment of chronic obstructive pulmonary disease with salmeterol and the additive effect of ipratropium.
We compared the effectiveness of inhaled formoterol with that of ipratropium in the treatment of chronic obstructive pulmonary disease (COPD). After a 2-wk run-in period, 780 patients with COPD were randomized to receive for 12 wk formoterol dry powder 12 or 24 microg twice daily, ipratropium bromide 40 microg four times daily, or placebo in a multicenter, double-blind, parallel-group study. The primary efficacy variable was the area under the curve for forced expiratory volume in 1 s (FEV(1)) measured over 12 h after 12 wk of treatment. Secondary variables included diary symptoms and quality of life. Both doses of formoterol and ipratropium significantly increased the area under the curve for FEV(1) in comparison with placebo (all p < 0.001). Both doses of formoterol were also significantly superior to ipratropium (all p < 0.025). Compared with placebo, both doses of formoterol significantly improved symptoms (all p < or = 0.007) and quality of life (p < 0.01 for total scores) whereas ipratropium did not show significant effects (all p > or = 0.3). All study treatments exhibited a similar safety profile. We conclude that formoterol is more effective than ipratropium bromide in the treatment of COPD, as the efficacy of ipratropium on airflow obstruction does not translate into a clinical benefit that patients can perceive. To examine and compare the efficacy and safety of salmeterol xinafoate, a long-acting inhaled beta2-adrenergic agonist, with inhaled ipratropium bromide and inhaled placebo in patients with COPD.
                A stratified, randomized, double-blind, double-dummy, placebo-controlled, parallel group clinical trial.
                Multiple sites at clinics and university medical centers throughout the United States.
                Four hundred eleven symptomatic patients with COPD with FEV1 < or = 65% predicted and no clinically significant concurrent disease. Interventions: Comparison of inhaled salmeterol (42 microg twice daily), inhaled ipratropium bromide (36 microg four times a day), and inhaled placebo (2 puffs four times a day) over 12 weeks.
                Salmeterol xinafoate was significantly (p < 0.0001) better than placebo and ipratropium in improving lung function at the recommended doses over the 12-week trial. Both salmeterol and ipratropium reduced dyspnea related to activities of daily living compared with placebo; this improvement was associated with reduced use of supplemental albuterol. Analyses of time to first COPD exacerbation revealed salmeterol to be superior to placebo and ipratropium (p < 0.05). Adverse effects were similar among the three treatments.
                These collective data support the use of salmeterol as first-line bronchodilator therapy for the long-term treatment of airflow obstruction in patients with COPD. Chronic obstructive pulmonary disease (COPD) is a condition in which continuous bronchodilation may have clinical advantages. This study evaluated salmeterol, a beta-agonist bronchodilator with a duration of action substantially longer than that of short-acting beta-agonists, compared with ipratropium, an anticholinergic bronchodilator, and placebo in patients with COPD. Four hundred and five patients with COPD received either salmeterol 42 microg twice daily, ipratropium bromide 36 microg four times daily, or placebo for 12 wk in this randomized, double-blind, parallel-group study. Patients were stratified on the basis of bronchodilator response to albuterol (> 12% and > 200-ml improvement) and were randomized within each stratum. Bronchodilator response was measured over 12 h four times during the treatment period. Salmeterol provided similar maximal bronchodilatation to ipratropium but had a longer duration of action and a more constant bronchodilatory effect with no evidence of bronchodilator tolerance. Both active treatments were well tolerated. Salmeterol was an effective bronchodilator with a consistent effect over this 12-wk study in patients with COPD, including those "unresponsive" to albuterol. The long duration of action of salmeterol offers the advantage of twice daily dosing compared with the required four times a day dosing with ipratropium. The efficacy and safety of salmeterol alone was compared with the combination of salmeterol plus ipratropium and with placebo during long-term treatment in patients with stable chronic obstructive pulmonary disease. In addition, the single-dose effect in response to the first dose of treatment was studied 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-placebo parallel group study and were randomized after a run-in period of 2 weeks to receive either salmeterol 50 microg b.i.d., salmeterol 5 microg b.i.d. plus ipratropium 40 microg q.i.d. or placebo for a period of 12 weeks. The single-dose study demonstrated that salmeterol produced a significant increase in FEV1 (peak of 7% pred) and specific airway conductance (sGaw) (maximum of 60% baseline) for > or =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 salmeterol and the salmeterol plus ipratropium groups (p<0.001), with an associated decrease in the use of rescue salbutamol. Improvements in FEV1 and sGaw were greater in the salmeterol plus ipratropium group than in the patients receiving only salmeterol. Thirty-five patients had an exacerbation; 11 (23%) in the salmeterol group (versus placebo NS), six (13%) in the salmeterol plus ipratropium group (versus placebo p<0.01) and 18 (36%) in the placebo group. In conclusion, in patients with severe stable chronic obstructive pulmonary disease, long-term treatment with either salmeterol alone or salmeterol plus ipratropium is safe and effective. There was added benefit from the combination therapy in terms of improvement in airways obstruction, but not for improvement in symptom control or need for rescue salbutamol.