Long-term open evaluation of amlodipine vs hydrochlorothiazide in patients with essential hypertension.

The long-term efficacy and safety of amlodipine (2.5 to 10 mg) once daily was compared with that of hydrochlorothiazide (HCTZ) (25 to 100 mg) daily in 139 patients with mild-to-moderate hypertension. The study was a randomized, open-label, parallel comparison of 50 weeks' duration. Patients were randomized in a 2:1 ratio (amlodipine n = 92: HCTZ n = 47). Atenolol was added at week 12 if monotherapy was inadequate. At week 12, the mean reductions for supine and standing systolic and diastolic blood pressure values with amlodipine were found to be -15.2/-12.3 mmHg and -14.0/-11.6 mmHg respectively, as compared to -15.5/-11.1 mmHg and -16.1/-10.1 mmHg after treatment with HCTZ. The percentage of patients responding to treatment at week 12 was 74% on amlodipine and 70% on HCTZ. The addition of atenolol in those patients not adequately controlled on monotherapy produced additional mean reductions in supine and standing systolic and diastolic pressures in both the amlodipine-atenolol group and in the HCTZ-atenolol group. The incidence of adverse effects was 47% with amlodipine and 26% with HCTZ at 12 weeks. Overall, six patients were discontinued because of side effects while receiving amlodipine monotherapy and one from the HCTZ monotherapy group; none were discontinued because of side effects on combination therapy. Laboratory test abnormalities were reported by 16% of amlodipine-treated patients compared with 63% of patients on HCTZ. The antihypertensive effects of amlodipine and hydrochlorothiazide appeared to be comparable and were maintained during long-term therapy.

Dose-dependent effects of betaxolol in hypertension: a double-blind, multicenter study.

This study determined the dose-response relationship among three doses of betaxolol compared with placebo in patients with mild-to-moderate hypertension. In this double-blind, placebo-controlled trial, 317 hypertensive patients were randomly assigned to receive placebo or betaxolol 5, 10, or 20 mg once daily for 4 weeks. A significant (P less than .05) decrease in supine diastolic blood pressure (BP) compared with concurrent placebo was evident with all three doses of betaxolol after 1 week of active treatment. Each dose of betaxolol maintained a significant reduction in diastolic and systolic BP and heart rate responses throughout the 4-week treatment period. At the fourth week (final treatment evaluation), BP and heart rate were significantly (P less than .05) reduced by all three doses of betaxolol compared with placebo. For supine systolic and diastolic BP, the decreases with betaxolol 20 mg were significantly (P less than .05) greater than with the 5 mg dose, but there was no statistically significant difference between the 10-mg and either the 5- or 20-mg doses. For standing diastolic BP, the effect of betaxolol 5 mg once daily was significantly (P less than .05) less than that of 10 and 20 mg. The overall supine diastolic BP response to betaxolol was dose dependent, and more patients responded to the 10- and 20-mg doses of betaxolol (66% and 76%, respectively) than to the 5-mg dose (59%). For each efficacy variable, the absolute magnitude of the reduction was greater with increasing dose. In subgroup analyses, BP responses were analyzed by race, age, baseline BP, and age combined with baseline BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the antihypertensive effects of betaxolol and chlorthalidone as monotherapy and in combination.

In this multicenter, double-blind, parallel study, the antihypertensive effects of betaxolol (20 mg once daily) and/or chlorthalidone (25 mg once daily) were analyzed in 186 patients with essential hypertension. Following a 2- to 4-week placebo baseline period, patients were randomized to one of two treatment groups (betaxolol or chlorthalidone) and studied for 6 weeks while receiving single therapy and an additional 6 weeks with a combination of the two agents. Significant decreases from baseline supine diastolic blood pressure (SDBP) were observed in both groups at the end of the single-therapy phase (11 mm Hg in SDBP for betaxolol and 12 mm Hg in SDBP for chlorthalidone); a further significant decrease (7 mm Hg for betaxolol and 8 mm Hg for chlorthalidone in SDBP) was observed from the end of the single-therapy phase to the end of the combination-therapy phase. Changes in supine systolic blood pressure (SSBP) from baseline to the end of the single-therapy phase were 10 mm Hg for the betaxolol and 16 mm Hg for the chlorthalidone group. In all cases, within-group changes were statistically significant. From the end of single therapy to end of combination therapy there was an additional 14-mm Hg and 13-mm Hg reduction in SSBP in the betaxolol and chlorthalidone groups, respectively. Overall, 89% of the randomized patients completed the single-treatment phase (phase I), and 89% of those patients completed the combined therapy phase (phase II). There was no significant difference between treatment groups in the clinical response rate (SDBP at or below 90 mm Hg or a decrease from baseline of at least 10 mm Hg). A substantial percentage of patients completing phase I responded to either single agent (58% for betaxolol and 65% for chlorthalidone). Among patients completing phase II therapy, the combination of the two agents produced a greater response rate (83% for the betaxolol-first group and 85% for the chlorthalidone-first group). In conclusion, both agents were effective and well tolerated. The most frequent adverse events in the single-therapy phase were headache, arthralgia, and dizziness, while bradycardia, rhinitis, arthralgia, and dizziness were most frequent in the combination-therapy phase. The combination of betaxolol (20 mg) and chlorthalidone (25 mg) once daily produced an additive antihypertensive effect regardless of which drug was administered first.

Failure of zinc gluconate in treatment of acute upper respiratory tract infections.

Zinc is a trace metal with in vitro activity against rhinovirus, the major etiologic agent in acute upper respiratory tract infections (URIs). A previous trial of zinc gluconate supported its efficacy in treating URIs, but the effectiveness of blinding was uncertain. We conducted a prospective randomized trial of zinc gluconate versus a taste-matched placebo of sucrose octaacetate. Lozenges containing either 23 mg of elemental zinc or placebo were taken every 2 h. Eleven URI symptoms were rated daily on a scale of 0 (not present) to 3 (severe). Duration of illness, reflected in the proportion of subjects remaining symptomatic on each day, was not significantly reduced (maximum difference of 12.6% on day 7, P = 0.09; 95% confidence interval, -6 to 31%) by either treatment. Severity of illness, assessed by using a summed severity score, was reduced incrementally by 7 to 8% on days 5 to 7 (P = 0.02) in subjects taking zinc. Adverse effects, mostly nausea and altered taste, were reported by 50% of subjects taking zinc. We conclude that while zinc gluconate may produce a small reduction in overall severity of symptoms, this is not clinically significant. Given the additional high incidence of adverse effects, zinc gluconate cannot be recommended for use in the treatment of acute URIs.

Safety and efficacy of amlodipine added to hydrochlorothiazide therapy in essential hypertension.

We compared amlodipine, a dihydropyridine calcium antagonist, to placebo as add-on therapy to hydrochlorothiazide in 91 hypertensive patients inadequately controlled on hydrochlorothiazide (50 mg/d for four weeks). This was a double-blind, randomized, multicenter, parallel group-trial; 45 patients received placebo and 46 received amlodipine in doses of 2.5 to 10 mg qd (mean 9 mg/d). Supine blood pressure systolic/diastolic, mean +/- SE mm Hg) 24-hour postdose was significantly reduced by 14.2 +/- 2.3/11.7 +/- 1, compared to placebo, 4.5 +/- 2.7/5 +/- 1.2. Standing blood pressure was similarly reduced: amlodipine by 14 +/- 2.7/12.5 +/- 1.2; placebo by 3 +/- 2.1/5.8 +/- 1.2. This reduction in blood pressure was attained without any significant changes in pulse rate, EKG, and serum lipids (triglycerides were reduced in the amlodipine group by 42.9 mg/dL, P = .023). Only two patients had side effects requiring discontinuation from the study (both in the amlodipine group). Side effects occurred in 27 amlodipine-treated patients (11 with peripheral edema) and 18 patients in the placebo (three with peripheral edema) group. Investigator's assessment of therapeutic effect and tolerability, and the percent of responders v nonresponders was also in favor of amlodipine. Thus amlodipine administered once daily is an effective and safe agent for second-step therapy in mild to moderate essential hypertension.

Aetiology of acute pharyngitis and clinical response to empirical therapy with erythromycin versus amoxicillin.

One hundred and eighty-nine adults with acute pharyngitis had culture and serological evaluation for group A beta haemolytic streptococci (GABHS), Mycoplasma pneumoniae, and Branhamella catarrhalis. Sixteen patients had evidence for infection with GABHS, none for M. pneumoniae, and one for B. catarrhalis. For those with GABHS, there was no significant difference between empirical treatment by erythromycin or amoxicillin. For those without GABHS, empirical treatment with erythromycin appeared to result in a statistically significant reduction in cough and a noticeable but less than significant reduction of other symptoms when compared to empirical treatment with amoxicillin. The new formulation of erythromycin utilized in this study (PCE) may be associated with a reduction in gastrointestinal intolerance from that reported with other erythromycin products.

Long-term open evaluation of amlodipine versus hydrochlorothiazide in patients with essential hypertension.

Amlodipine, a long-acting calcium antagonist, was compared with hydrochlorothiazide (HCTZ) in a long-term study of 139 patients. After a 2-week placebo run-in period, patients were randomly allocated to receive either amlodipine or HCTZ in a 2:1 patient ratio. After study week 12, those patients whose hypertension was not controlled with either monotherapy had atenolol added to their regimen. The daily dose range for amlodipine was 2.5-10.0 mg and for HCTZ was 25-100 mg. At study week 12, 24-h postdose blood pressure was reduced in both amlodipine (-16/-12 mm Hg supine; -14/-12 mm Hg standing) and HCTZ (-16/-11 mm Hg supine; -16/-10 mm Hg standing) groups. Response was defined as a supine diastolic blood pressure of less than 90 mm Hg or its decrease by greater than or equal to 10 mm Hg. Responder rates at the end of 12 weeks' monotherapy were 74.1% for amlodipine and 69.8% for HCTZ. Forty percent of patients randomized to amlodipine and 45% randomized to HCTZ achieved adequate blood pressure control ("response" as defined above) with monotherapy alone over the whole 50-week treatment period. The incidence of treatment-related side effects up to study week 12 was 46.7% with amlodipine monotherapy and 25.5% with HCTZ monotherapy. Two patients were discontinued from amlodipine and one from HCTZ for side effects during the first 12 weeks of the study, and a further four from amlodipine after week 12; none were discontinued from combination therapy.(ABSTRACT TRUNCATED AT 250 WORDS)