This 30-center, randomized, double-blind, placebo-controlled, parallel-group study was designed to (1) establish that 6.25 mg of hydrochlorothiazide (HCTZ) given once daily with 5 mg of bisoprolol fumarate can contribute to antihypertensive effectiveness in patients with stage I and stage II (mild to moderate) systemic hypertension; and (2) assess whether this formulation was more effective or possessed a safety advantage over standard monotherapy with bisoprolol or 25 mg of HCTZ. Results showed that HCTZ 6.25 mg contributed significantly to the antihypertensive effectiveness of bisoprolol 5 mg. Bisoprolol 5 mg/HCTZ 6.25 mg (B5/H6.25) produced significantly greater mean reductions from baseline in sitting systolic and diastolic blood pressure (-15.8 mm Hg/-12.6 mm Hg) than bisoprolol 5 mg alone (-10.0 mm Hg/-10.5 mm Hg) and HCTZ 25 mg alone (-10.2 mm Hg/-8.5 mm Hg). A 73% response rate was achieved with the low-dose formulation compared with 61% for the bisoprolol 5 mg (B5) group and 47% for the HCTZ 25 mg (H25) group. B5/H6.25 was found to be significantly more effective than B5 or H25 in all subgroups of patients, regardless of gender, race, age, or smoking history. Antihypertensive effects were maintained during the 24-hour dosing interval. The incremental effectiveness of B5/H6.25 was not accompanied by an increase in the frequency or severity of adverse experiences; the incidence of adverse experiences in the B5/H6.25 group was comparable to that in the placebo group. B5/H6.25 was shown to provide safety advantages over H25, as shown by less hypokalemia (< 1% with B5/H6.25 versus 6.5% with H25).(ABSTRACT TRUNCATED AT 250 WORDS)
The utility of factorial design trials to characterize dose-response relationships and to test the potential interactions between various antihypertensive agents has been demonstrated. The combination of low dosages of bisoprolol and hydrochlorothiazide may be a rational alternative to conventional stepped-care therapy for the initial treatment of patients with mild to moderate hypertension.
By giving diazoxide intravenously and furosemide orally the diastolic blood pressure was kept under 110 mm Hg and the urinary output over 1 L/day for a 2-week period in 25 hypertensive patients with azotemia. During the first 2 weeks of treatment three patients died. Although the 40% decrease in mean arterial pressure in the remaining patients was associated with immediate improvement in the cardiovascular status, for example, clearing of congestive heart failure and papilledema, there was a 19% average increase in BUN and 17% average increase in serum creatinine values. Three months later, however, maintenance of the reduced arterial pressure was associated with average reductions of 24 mg/1100 ml in BUN and of 2.8 mg/100 ml in serum creatinine below control values. Each of the patients who remained on therapy continued to do well. Twenty-six months later six additional patients had died. In the remaining 16 patients the average mean arterial pressure was 117 mm Hg; papilledema had cleared; the average concentration of BUN was 22 mg/100 ml; the average serum creatinine was 1.8 mg/ 100 ml.
This study assessed the antihypertensive efficacy and side effects of clonidine administered transdermally. Twenty-five patients with mild to moderate essential hypertension (seated diastolic blood pressure 95-120 mm Hg with diuretic therapy alone) controlled with oral diuretic plus oral clonidine were enrolled. Transdermal clonidine was substituted for oral clonidine and titrated until adequate blood pressure control (seated diastolic blood pressure less than 90 mm Hg) was attained. At the end of titration, seated morning blood pressure averaged 129/90 +/- 15/5 mm Hg (mean +/- standard deviation) compared to 136/96 +/- 13/7 mm Hg (p less than 0.01/0.001) during oral clonidine administration. Standing morning blood pressure was also lower during transdermal than oral therapy (131/94 +/- 16/5 vs 136/99 +/- 14/7, p less than 0.05/0.001). Afternoon blood pressures (at peak effect of oral dose) were virtually identical during oral and transdermal therapy in both seated and standing positions. Typical side effects of oral clonidine, including dry mouth, drowsiness, and sexual dysfunction, were reduced during transdermal therapy. There was less morning-to-afternoon variability of blood pressure control and plasma clonidine concentrations during transdermal than during oral therapy. One patient left the study because of drowsiness and two because of skin reactions to the transdermal skin patch. Mild transient local skin irritation occurred frequently. Transdermal clonidine plus a diuretic is an effective treatment for mild to moderate essential hypertension, improves compliance and reduces side effects of therapy.
The immediate fall in arterial pressure following furosemide in the 17 hypertensive patients studied was asociated with a decrease in plasma volume, cardiac output, and extracellular fluid volume, and an increase in urinary sodium excretion. A glucose infusion administered at the trough of hypotension in an amount exceeding the urinary output resulted in the return of arterial pressure to control levels in each patient. Although an increase in plasma volume was noted in each patient, it was significantly below control levels. The central venous pressure, cardiac output, and state of negative sodium balance following the glucose infusion remained unchanged, but the extracellular fluid volume had re-expanded. It would seem that the changes in arterial pressure either after furosemide or during the glucose infusion were related to changes in extracellular fluid. The fact that a decreased pressor response to norepinephrine following furosemide was associated with a decrease in extracellular fluid and the fact that expansion of extracellular fluid with glucose restored the pressor response to normal further document the importance of the extracellular fluid in the regulation of arterial pressure.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.