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Background: Most treated hypertensive patients do not achieve adequate blood pressure (BP) control. Initiating therapy with two drugs has been suggested when BP is >20/10 mm Hg above goal. To ensure patients' compliance, such treatment needs to be well tolerated and must not compromise health-related quality of life (HRQL). The primary objective of this study was to compare the effects on HRQL of initiating treatment with felodipine + metoprolol (F+M) fixed combination tablets, or enalapril (E), or placebo (P)., Methods: A total of 947 patients of both sexes with primary hypertension (diastolic BP 95 to 110 mm Hg), aged 20 to 70 years, participated in this randomized, double-blind, parallel group, 12-week, multicenter trial. Treatment was initiated with F+M 5 + 50 mg, or E 10 mg, or P. Doses were doubled after 4 or 8 weeks if diastolic BP was >90 mm Hg. The HRQL was measured at baseline and at the last visit using two validated questionnaires: the Psychological General Well-being Index (PGWB) and the Subjective Symptom Assessment Profile (SSA-P). Office BP was measured at trough, that is, 24 h after the previous dose., Results: The HRQL was high at baseline and generally well maintained during the study. For example, the mean (SD) PGWB total score was 104 (16) at baseline and 105 (16) at 12 weeks in all three treatment groups. The BP reductions after F+M (18/14 mm Hg) and E (12/9 mm Hg) were significantly greater than after P (7/7 mm Hg), and the reduction after F+M was significantly greater than after E., Conclusions: The HRQL is maintained in the presence of substantial BP reduction during antihypertensive treatment with F+M fixed combination tablets.

The aim of the present study was to assess the efficacy and tolerability of a calcium antagonist/beta-blocker fixed combination tablet used as first-line antihypertesnive therapy in comparison with an angiotensin converting enzyme inhibitor and placebo. Patients with uncomplicated essential hypertension (diastolic blood pressure between 95 and 110 mm Hg at the end of a 4-week run-in period) were randomly allocated to a double-blind, 12-week treatment with either a combination tablet of felodipine and metoprolol (Logimax), 5/50 mg daily (n = 321), enalapril, 10 mg daily (n = 321), or placebo (n = 304), with the possibility of doubling the dose after 4 or 8 weeks of treatment if needed (diastolic blood pressure remaining >90 mm Hg). The combined felodipine-metoprolol treatment controlled blood pressure (diastolic < or =90 mm Hg 24 h after dose) in 72% of patients after 12 weeks, as compared with 49% for enalapril and 30% for placebo. A dose adjustment was required in 38% of patients receiving the combination, in 63% of patients allocated to placebo, and 61% of enalapril-treated patients. The overall incidence of adverse events was 54.5% during felodipine-metoprolol treatment; the corresponding values for enalapril and placebo were 51.7% and 47.4%, respectively. Withdrawal of treatment due to adverse events occurred in 18 patients treated with the combination, in 10 patients on enalapril, and 12 patients on placebo. No significant change in patients' well-being was observed in either of the three study groups. These results show that a fixed combination tablet of felodipine and metoprolol allows to normalize blood pressure in a substantially larger fraction of patients than enalapril given alone. This improved efficacy is obtained without impairing the tolerability. The fixed-dose combination of felodipine and metoprolol, therefore, may become a valuable option to initiate antihypertensive treatment.

In a double-blind, placebo-controlled trial, patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) were randomly allocated to oral treatment with sparfloxacin (200 mg loading dose followed by 100 mg once daily) or amoxycillin/clavulanic acid (500 mg/125 mg tds) for a total treatment duration of 7 to 14 days. Patients were evaluable if they had a FEV1/FVC ratio of less than 70% at stable state and presented with a suspected infectious exacerbation defined as increases in dyspnoea, sputum volume and sputum purulence. The primary efficacy variable was the overall success (defined as disappearance or improvement of dyspnoea and reductions in sputum volume and purulence) at end of treatment and follow-up. Overall efficacy was assessed in both the intent-to-treat (728 patients) and the evaluable (351 patients) populations. At the end of treatment and follow-up, success rates were identical for the sparfloxacin (87.3% and 78.7%) and amoxycillin-clavulanic acid (88.8% and 79.8%) treatment groups. Similar figures were found for the intent-to-treat population. The analysis of drug safety was similar for both treatment groups. The most frequently encountered pathogens were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Sparfloxacin appeared superior for bacteriological eradication of Haemophilus influenzae, and Moraxella catarrhalis. Sparfloxacin in a single daily dose appears at least as effective as amoxycillin/clavulanic acid in the treatment of patients with acute exacerbations of COPD.

A pooled data analysis of two double-blind studies encompassing 1137 episodes of community-acquired pneumonia in hospitalised adults, of which 560 were treated with sparfloxacin and 577 were randomised to comparator antibacterial agents (amoxycillin/clavulanic acid, erythromycin or amoxycillin administered at reference dosages), was performed. The global efficacy rate at the end of treatment in evaluable patients treated with sparfloxacin was 88.3% compared with 84.1% in those who received comparator antibacterial agents. This analysis verified the efficacy of this new aminofluoroquinolone, given orally once daily, in the treatment of community acquired pneumonia. The overall outcome favoured sparfloxacin for use in the empirical treatment of community-acquired pneumonia.

A multicentre, double-blind, randomized study was conducted in patients with osteoarthritis (OA) of the hip or knee in order to compare the efficacy and safety of the new cyclooxygenase-2 (COX-2) inhibitor, meloxicam, with diclofenac sodium, a conventional treatment for this condition. Three hundred and thirty-six patients were treated with oral meloxicam 7.5 mg once daily or diclofenac 100 mg slow release once daily for 6 months. There were no significant differences between the treatment groups with respect to overall pain, pain on movement, global efficacy or quality of life scores at the end of treatment, all of which showed good levels of improvement. Sixty-six patients were withdrawn after the start of the double-blind phase due to adverse events (n = 21, meloxicam; n = 31, diclofenac) or to lack of efficacy (seven in each group). The median of dose paracetamol taken concomitantly was statistically significantly lower in the meloxicam group than in the diclofenac group (185 vs 245 mg/day; P = 0.0123) with a comparable proportion of patients taking concomitant paracetamol therapy in both groups. Both drugs were well tolerated, although severe adverse events, treatment withdrawal and clinically significant laboratory abnormalities were more common with diclofenac than with meloxicam. Thus, meloxicam 7.5 mg is a safe and effective treatment for OA of the hip and knee which demonstrates a trend towards an improved safety profile compared with diclofenac.

The safety and efficacy of dirithromycin and clarithromycin were compared in a single-blind, multicentre study of patients with acute bacterial exacerbation of chronic bronchitis (AECB). Patients received either dirithromycin, 500 mg once daily for 5 days, or clarithromycin, 250 mg twice daily for 7 days. A total of 212 patients entered the study, of whom 191 qualified for efficacy analysis. Favourable post-therapy clinical and bacteriological response rates for qualified patients (95 dirithromycin and 96 clarithromycin) were similar: 89.5% and 68.8% for dirithromycin vs 94.8% and 71.9% for clarithromycin. At late post-therapy evaluation, favourable clinical and bacteriological response rates were achieved in 98.8% and 96.2% of dirithromycin patients and 95.3% and 93.3% of clarithromycin patients, respectively. These differences were neither statistically nor clinically significantly different. Both drugs had similar efficacy against Haemophilus influenzae and both were well tolerated. Dirithromycin, administered as a single daily dose for just 5 days resulted in complete compliance in all but four patients. In clarithromycin-treated patients, requiring a 7-day course of twice-daily treatment, compliance was less satisfactory, with 12 patients failing to comply, though the between-group difference was not statistically significant. It can be concluded that 5 days of dirithromycin, 500 mg once daily is as safe and effective as 7 days of clarithromycin, 250 mg, twice daily in the treatment of AECB.

Three hundred and fifteen patients were randomly allocated to treatment for six months with bisoprolol 5 or 10 mg day-1 or atenolol, 50 mg day-1, in a double-blind, double-dummy parallel group, international multicentre study. Two hundred and ninety-two (175 men and 117 women) were eligible for statistical follow-up. Their mean age was 52.6 years (range 28-70). All patients had a supine diastolic blood pressure of 95-120 mmHg on two occasions during the four weeks of placebo treatment. Twenty-four patients ended the study prematurely and a further 19 had their regimes changed because of an insufficient effect. The reasons for drop-out were similar in the three treatment groups. Thus, 249 patients continued to receive the treatment they were allocated to, with 80, 83 and 86 patients in the three respective groups. The sex and age distributions and the number of previously treated hypertensives were similar in the three groups. At the end of placebo treatment the supine blood pressures in the three groups (bisoprolol 5 or 10 mg day-1 or atenolol 50 mg day-1, respectively) were 163.9/102.5, 157.4/101.8 and 160.0/102.2 mmHg, respectively. The systolic blood pressure was higher (P less than 0.05) in the group receiving bisoprolol 5 mg day-1 than in the 10 mg day-1 group. After 26 weeks of treatment the supine blood pressures in the three groups were 150.6/90.8, 142.0/89.1 and 148.6/91.7 mmHg, respectively. The largest estimated difference in blood pressure reduction was 4.6/2.3 mmHg between the group receiving bisoprolol 10 mg day-1 and the group receiving atenolol 50 mg day-1. A reduction in mean blood pressure of greater than or equal to 10 mmHg was noted in 66% of the patients in the bisoprolol group (10 mg day-1), in the other groups 66 and 59%, n.s. Bisoprolol is effective, well-tolerated and safe in the treatment of hypertension. A daily dose of 5 mg seems recommendable for the majority of hypertensive patients and seems equipotent with 50 mg day-1 of atenolol in the present study.