benazepril and Edema

This multicentre, double-blind, trial in subjects with severe hypertension compared the efficacy and tolerability of two parallel drug regimens: A/B (amlodipine/benazepril: 5/20 or 10/40 mg daily, if necessary) with A (amlodipine: 5 or 10 mg daily, if necessary). The principal dependent variable was the proportion of patients achieving goal blood pressures (BP<140/90 mm Hg or BP<130/80 mm Hg in diabetes or chronic kidney disease) in the two groups within 6 weeks. In the 259 randomized subjects, BP control rates were higher with A/B at 2, 4 and 6 weeks (10.5, 22, and 33.6%, respectively) compared with A (5.7, 16, and 25.8 %, respectively). Corresponding trended BP reductions from baseline at 2, 4 and 6 weeks were about 5 mm Hg greater with A/B (-21+/-16, -26+/-17 and -30+/-17 mm Hg, respectively, compared with A (-16+/-17, -23+/-18 and 25+/-19 mm Hg, respectively, P<0.01). Both regimens were well tolerated; incidences of peripheral oedema at weeks 4 and 6 were similar (A/B: 13 and 20% versus A: 20 and 22%, P=not significant). We conclude that titration of amlodipine and benazepril in single-pill combinations is more effective than titration of amlodipine alone for rapid BP control in patients with severe hypertension.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Benzazepines; Chronic Disease; Diabetes Complications; Drug Therapy, Combination; Edema; Female; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Treatment Outcome; Young Adult

The Seventh Report of the Joint National Committee (JNC 7) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends initial combination therapy for patients whose blood pressure (BP) is >20/10 mm Hg above goal. This study evaluated the efficacy and safety of initial combination therapy versus that of monotherapy in patients with stage 2 hypertension, who by definition meet the JNC 7 recommendation for initial combination antihypertensive therapy.. This multicenter, double-blind, 12-week study randomized 364 patients with stage 2 hypertension to fixed-dose combination therapy with amlodipine besylate/benazepril HCl (5/20 mg/d titrated to 10/20 mg/d) or amlodipine besylate monotherapy (5 mg/d titrated to 10 mg/d).. Significantly more patients randomized to combination therapy (74.2%) compared with those randomized to monotherapy (53.9%; P <.0001) achieved the primary end point (reductions in systolic BP > or =25 mm Hg, if baseline systolic BP was <180 mm Hg, or > or =32 mm Hg, if baseline systolic BP was > or =180 mm Hg). Significantly more patients randomized to combination therapy compared with monotherapy attained BP goals of <140/90 mm Hg (61.0% v 43.3%; P =.0007) and < or =130/85 mm Hg (35.7% v 19.1%; P =.0004). Among patients with baseline systolic BP > or =180 mm Hg, combination therapy resulted in significantly greater reductions in systolic BP compared with monotherapy (-42.3 v -30.4 mm Hg; P =.001). More than 90% of patients in each group were titrated to the higher dose. Both treatments were well tolerated.. Combination therapy was well tolerated and resulted in significantly greater BP reductions and attainment of BP goals compared with monotherapy in patients with stage 2 hypertension. This evidence supports the recommendation of combination therapy as first-line treatment in stage 2 hypertension.

Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Calcium Channel Blockers; Diastole; Dose-Response Relationship, Drug; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; Edema; Female; Humans; Hypertension; Male; Middle Aged; Severity of Illness Index; Systole; Treatment Outcome

The aim of this study was to evaluate the effect of benazepril addition to amlodipine antihypertensive treatment on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP), two objective measures of ankle oedema. A total of 32 mild to moderate essential hypertensives (DBP>90 and <110 mmHg), aged 30-70 years were studied. After a 4-week placebo period, they were randomized to amlodipine 5 mg o.d. or benazepril 10 mg o.d. or amlodipine 5 mg plus benazepril 10 mg o.d. for 4 weeks, according to a crossover design. At the end of the placebo period and of each active treatment period, blood pressure,AFV and PSTP were evaluated. AFV was measured using the principle of water displacement. PSTP was assessed using a system, the subcutaneous pretibial interstitial environment with a water manometer. Both amlodipine and benazepril monotherapy significantly reduced SBP (-18.2+/-4 and -17.8+/-4 mmHg, respectively, P<0.01 vs baseline) and DBP (-12.1+/-3 and -11.7+/-3 mmHg, respectively, P<0.01); the reduction was increased by the combination (-24.2+/-5 mmHg for SBP, P<0.001 and -16.8+/-4 mmHg for DBP, P<0.001). Amlodipine monotherapy significantly increased both AFV (+17.1%, P<0.001 vs baseline) and PSTP (+56.6%, P<0.001 vs baseline). As compared to amlodipine alone, the combination produced a less pronounced increase in AFV (+5.5%, P<0.05 vs baseline and P<0.01 vs amlodipine) and PSTP (+20.5%, P<0.05 vs baseline and P<0.01 vs amlodipine). Ankle oedema was clinically evident in 11 patients with amlodipine monotherapy and in three patients with the combination. These results suggest that ACE-inhibitors partially counteract the microcirculatory changes responsible for Ca-antagonists-induced oedema formation.

Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Ankle; Benzazepines; Calcium Channel Blockers; Cross-Over Studies; Diagnostic Techniques, Cardiovascular; Double-Blind Method; Drug Therapy, Combination; Edema; Female; Humans; Hydrostatic Pressure; Hypertension; Male; Middle Aged

Community-based studies are conducted to determine the degree to which therapeutic interventions will succeed in real world settings. This large practice-based clinical trial assessed the efficacy and tolerability of fixed-dose combination therapy with amlodipine/benazepril, compared with amlodipine monotherapy, in patients with mild-to-moderate hypertension.. Hypertensive patients currently taking amlodipine were selected based on one of two criteria: inadequate blood pressure (BP) control on amlodipine (diastolic BP [DBP] > or = 90 mm Hg; group 1), or inability to tolerate amlodipine (DBP < or = 90 mm Hg, but with edema; group 2). Eligible patients were switched from 5 or 10 mg of amlodipine to 5/10 mg or 5/20 mg of amlodipine/benazepril for 4 weeks. In group 1 (n = 6410), primary efficacy outcome was change in mean sitting DBP. A secondary efficacy outcome was change in mean sitting systolic BP (SBP). In group 2 (n = 1502), primary efficacy outcome was the percentage of patients whose edema improved during therapy with amlodipine/benazepril when compared with amlodipine monotherapy.. In group 1, mean sitting DBP declined from 96.5 mm Hg at baseline to 84.9 mm Hg at week 4, a mean reduction of 11.5 mm Hg (95% confidence interval [CI] -11.8 to -11.3 mm Hg; P < .001). From baseline to week 4, mean sitting SBP declined from 152.9 mm Hg to 137.3 mm Hg, a mean reduction of 15.6 mm Hg (95% CI -16.0 to -15.2 mm Hg; P < .001). In group 2, 85% (95% CI 83%-87%) experienced some improvement in edema compared with baseline levels.. Fixed-dose combination antihypertensive agent amlodipine/benazepril was safe and effective for patients who experienced either inadequate BP control or edema with amlodipine monotherapy.

Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Calcium Channel Blockers; Drug Combinations; Edema; Female; Humans; Hypertension; Male; Middle Aged; Treatment Outcome