Francine Archambault

Antihypertensive effects of amlodipine and hydrochlorothiazide in elderly patients with ambulatory hypertension

Recent studies and authorities have advocated the use of low-dose thiazide diuretics as first-line treatment agents in elderly hypertensives. However, these recommendations were based solely on blood pressure (BP) measured in the clinic. The objective of the present 32-week double-blind study was to compare the effects of hydrochlorothiazide (HCTZ) and amlodipine (AML) in elderly patients with confirmed ambulatory hypertension. After a 4-week placebo washout period, 42 (25 men, 17 women) patients (mean age, 69 years) with clinic sitting diastolic BP of 95 to 114 mm Hg and daytime ambulatory diastolic BP of > or = 90 mm Hg were randomized double-blind to receive AML 5 to 10 mg (n = 21) or HCTZ 12.5 to 25 mg (n = 21) once daily. After 8 weeks of monotherapy, patients in whom clinic diastolic BP remained > or = 90 mm Hg were given combination therapy with the other agent. Amlodipine monotherapy induced significant reductions in clinic, mean 24-h, daytime and sleep systolic/diastolic BPs whereas only clinic BP decreased significantly in patients treated with HCTZ monotherapy. Moreover, 19/21 versus 8/21 patients on AML and HCTZ monotherapies achieved adequate BP control. At the end of the 32-week treatment period, combination therapy in the HCTZ group resulted in statistically significant reductions in clinic as well as in 24-h, daytime and sleep ambulatory BPs that were similar to those observed in the AML monotherapy group. In conclusion, the administration of AML monotherapy induced significant reductions in both clinic and ambulatory BPs in elderly patients whereas only clinic BP was significantly decreased by HCTZ monotherapy. Moreover, the addition of AML to HCTZ in patients inadequately controlled by monotherapy has permitted statistically significant decrements in clinic as well as in ambulatory BP. Consequently, the results of the present study suggest that the use of HCTZ in doses of up to 25 mg daily is inadequate for ambulatory BP control in the elderly despite official recommendations.

A Double-Blind Crossover Comparison of Nebivolol and Lisinopril in the Treatment of Ambulatory Hypertension.

Twenty-four-hour ambulatory blood pressure (ABP) monitoring was used as a measure of drug efficacy and criterion for inclusion of 29 patients with primary hypertension in a double-blind crossover comparison of the novel cardioselective β-blocker nebivolol (2.5–10 mg) with lisinopril (10–40 mg) once daily. After 8 weeks of therapy, both regimens reduced clinic BP to a similar and significant extent. Similar and significant reductions in systolic and diastolic ABP in every one of the 24-h periods were observed with both treatments. Moreover, the percentages of “BP loads” were lowered similarly from 64% to 31% and 30% with nebivolol and lisinopril, respectively. Furthermore, a comparable trough: peak ratio of 70% was obtained with both therapies. These data demonstrate that both once daily nebivolol and lisinopril given as monotherapies in patients with ambulatory hypertension provide adequate and similar clinic and ambulatory BP control. In addition, our findings indicate that ABP monitoring may improve the clinical evaluation of new antihypertensive agents.

The antihypertensive efficacy of the novel calcium antagonist mibefradil in comparison with nifedipine GITS in moderate to severe hypertensives with ambulatory hypertension

Mibefradil is a novel calcium antagonist that blocks selectively the T-type calcium channels. In this double-blind forced titration study design we compared the effects of mibefradil 50, 100, and 150 mg and nifedipine GITS 30, 60, and 90 mg monotherapies or combined with lisinopril 20 mg in 71 moderate to severe hypertensives (59 men and 12 women) with confirmed ambulatory hypertension. An incremental dose-response effect was observed both in clinic and ambulatory blood pressure parameters during treatment with mibefradil and nifedipine GITS alone and combined with lisinopril. At maximal dosage, patients treated with mibefradil experienced a greater (P < .05) reduction in clinic and ambulatory diastolic blood pressures as well as a greater response rate (86% v 69%). Trough:peak ratios for systolic and diastolic blood pressures were > 90% at each dose level. Significant decrease in baseline heart rate was observed with mibefradil 150 mg alone or combined with lisinopril, but no patients experienced clinically significant atrioventricular conduction abnormalities. Adverse events related to vasodilation were more prevalent in the nifedipine GITS group. Consequently, the results of the present study demonstrate that the novel calcium channel blocker mibefradil, either alone or in combination with lisinopril, is effective in reducing clinic and 24-h blood pressures while decreasing heart rate and is well tolerated in patients with moderate to severe hypertension.

Comparative assessment of antihypertensive efficacy of DL-nebivolol and D-nebivolol in patients with confirmed mild to moderate hypertension

We compared the antihypertensive activity of DL- and D-nebivolol in patients with essential hypertension on clinic and 24-h ambulatory blood pressure (BP) and during dynamic exercise as well. After a 4-week placebo run-in period, 30 patients (mean age 48 years) were randomly allocated to double-blind treatment with either DL-nebivolol 5 mg or D-nebivolol 2.5 mg once daily for 4 weeks. After an interim single-blind placebo washout of 2-4 weeks, all patients crossed over double-blind to the alternative DL- or D-nebivolol treatment for 4 weeks. The results show that DL- and D-nebivolol produced similar reductions in clinic trough (delta systolic/delta diastolic BP (delta SBP/delta DBP): -10/-8 and -13/-9 mm Hg, respectively, all p < 0.0001 vs. placebo), 24-h ambulatory (-12/-11 and -13/-11 mm Hg, respectively, all p < 0.0001), and peak exercise BP (-13/-6, both p < 0.01; and -13/-7 mm Hg, both p < 0.0001, respectively) as compared with placebo (SBP/DBP clinic 147/99, ambulatory 147/94, exercise 211/103 mm Hg). Our results showing superimposable clinic and ambulatory BP profiles as well as exercise BP responses with DL- and D-nebivolol treatment do not confirm results of animal pharmacologic experiments in which the L-isomer potentiated the antihypertensive effect of the D-isomer.

ACE Inhibitors as First-Line Treatment Agents: A Comparative Study of Trandolapril and Enalapril on Casual and Ambulatory Blood Pressures.

This double-blind, randomized, parallel-group study was designed to compare the efficacy of the angiotensin-converting enzyme inhibitors, trandolapril and enalapril, in 65 patients with mild to moderate primary hypertension. After a 4-week, single-blind, placebo run-in period, patients were randomized to receive either trandolapril 0.5 mg or enalapril 2.5 mg once daily. At 2-week intervals, trandolapril was titrated to 1, 2, or 4 mg and enalapril to 5, 10, or 20 mg in order to achieve a goal supine diastolic blood pressure (BP) of < 90 mm Hg. In addition to casual BP measurement, 24-h ambulatory BP monitoring was performed at the end of the placebo period (baseline) and after 10 weeks of stable therapy at optimal and/or maximal dosage.Both drugs induced significant and comparable decreases in clinic systolic and diastolic BPs. The mean doses used were 3.2 mg for trandolapril and 16.6 mg of enalapril. The maximal effect was obtained at the highest dosage for both drugs in most patients with a mean decrease in supine diastolic BP of 8.6 mm Hg and 7.3 mm Hg for trandolapril 4 mg and enalapril 20 mg, respectively. Moreover, both agents significantly and similarly reduced mean 24-h as well as awake and sleep ambulatory BPs. Heart rates remained unchanged throughout the study.Our results demonstrate that both trandolapril and enalapril given at high dose exhibited significant decreases in clinic as well as in 24-h, awake, and sleep ambulatory BPs with no clear-cut difference between the two treatment regimens. Moreover, our results emphasize the role of ambulatory BP monitoring when assessing the efficacy as well as the duration of action of new antihypertensive agents.