Patients were permitted to use their usual bronchodilator therapy throughout the study (Table 1) except during the 10-h period before a clinic visit. No antihypertensive agents other than the trial medications were allowed. Throughout the 12-week study, patients had 24-h telephone access to a doctor, and were encouraged to report even minor changes in respiratory and other symptoms.
After a single-blind two-week placebo run-in period, the patients were randomly given in a double-blind manner either 100 mg atenolol or 400 mg celiprolol daily for four weeks. Thereafter, all patients completed a two-week placebo crossover period and then received the alternative beta-blocker daily for a further four-week period (Fig 1).
Patients were seen every two weeks. At each visit, blood pressure with the patient in the supine and erect positions and pulse rates were recorded 24 h after the last dose of study medication. All blood pressure readings were made on the right arm, between 0800 and 0900, and after at least 5 min of seated rest. Click Here
Readings were repeated after the patient was at least 1 min in the supine or erect position. Disappearance of Korotkoff 5 sounds was the diastolic pressure, and the mean of three consecutive readings was taken for each measurement.
A single-dose challenge was then performed as follows: first, the best of three consecutive predose pulmonary function tests (FVC and FEV, measured on a Vitalograph and PEF measured with a mini-Wright peak flow meter) were obtained by a trained respiratory technologist. A single oral dose (placebo, 100 mg atenolol or 400 mg celiprolol) was then administered and respiratory function tests were repeated after 30 min, 1, 2 and 3 hours. At 3 h, a 200-p.g dose of inhaled salbutamol was administered, and spirometry was performed after 5 and 15 min.
Figure 1. Trial design.