Comparative effects of felodipine ER, amlodipine and nifedipine GITS on 24 h blood pressure control and trough to peak ratios in mild to moderate ambulatory hypertension: a forced titration study.

OBJECTIVE: To evaluate the 24 h antihypertensive efficacy and duration of action of felodipine extended release (ER) in comparison with two other long acting dihydropyridine calcium antagonists, amlodipine and nifedipine gastrointestinal therapeutic system (GITS), in patients with mild to moderate essential hypertension substantiated by ambulatory blood pressure (BP) monitoring. DESIGN: Randomized, forced titration, parallel group study. Clinic BP was measured at every patient's visit, and 24 h ambulatory BP was monitored at baseline and at the end of each dose-titration period. SETTING: Single centre: hypertension research unit in Quebec City, Quebec. PATIENTS: There were 89 patients enrolled into the study. Eighty-four eligible patients were randomized, and 83 completed the study and were included in the final efficacy analysis. INTERVENTIONS: Following a two-to four-week washout period (baseline), patients were randomly allocated to receive felodipine ER 5 mg, amlodipine 5 mg or nifedipine GITS 30 mg for four weeks (low dose). All study patients had their daily dose doubled to felodipine ER 10 mg, amlodipine 10 mg or nifedipine GITS 60 mg for a further four weeks (high dose). MAIN RESULTS: Significant (P < 0.001) and similar changes from baseline in clinic BP were observed in all treatment groups for low and high doses. Ambulatory BP profiles showed comparable blood pressure reductions with felodipine ER and amlodipine, and a trend towards a lesser reduction with nifedipine GITS during 24 h, daytime and night-time periods. BP loads were similarly reduced with the three treatments. Trough to peak ratios (T:Ps) were calculated from 24 h ambulatory BP curves according to two different approaches: for diastolic and systolic BP, respectively, the global approach produced T:Ps of 0.49 and 0.50 with felodipine ER 5 mg; 0.50 and 0.34 with felodipine ER 10 mg; 0.70 and 0.60 with amlodipine 5 mg; 0.88 and 0.82 with amlodipine 10 mg; 0.65 and 0.55 with nifedipine GITS 30 mg; 0.68 and 0.53 with nifedipine GITS 60 mg. T:Ps in the individual approach were 0.07 and 0.10 with felodipine ER 5 mg; 0.23 and 0.31 with felodipine ER 10 mg; 0.22 and 0.31 with amlodipine 5 mg; 0.45 and 0.58 with amlodipine 10 mg; 0.27 and 0.31 with nifedipine GITS 30 mg; and 0.24 and 0.40 with nifedipine GITS 60 mg. CONCLUSION: There was no evidence in this study of a difference among felodipine ER, amlodipine and nifedipine GITS in lowering ambulatory or clinic BP. Treatment based on ambulatory BP may be preferable to treatment guided by T:Ps because ambulatory BP is firmly established as a predictor of cardiovascular risk. Furthermore, there is no consensus on how to calculate T:Ps, and different methods of calculation may give divergent results.

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.

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.

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.

Physical abuse in Canadian runaway adolescents.

Recent studies with Canadian runaway youth have questioned the prevalence of abuse experienced by teenaged runaways and the causal contribution of such abuse to runaway experiences (Kufeldt, Duriux, Nimmo, & McDonald, 1992; Kufeldt, & Perry, 1989). This is a descriptive investigation of the physical abuse experienced in a sample of 195 Canadian adolescent runaways: the occurrence, nature and frequency of abuse, the age of onset and duration of abuse, the relationship between the victim and the perpetrator(s), and, who, if anyone, knew of the abuse. This investigation compared and contrasted the physical abuse experienced prior and subsequent to runaway experiences. In this sample, 86% of the population (74% of the males and 90% of the females) reported at least one physically abusive experience. The data reported suggest that this population of adolescents have been the victims of chronic, extreme abuse, experienced at a young age, often perpetrated by the biological parent (most often the mother), and was initiated prior to the first runaway episode. Female runaways were at greater risk than males for all types of abuse experience. Once youths left home, the physical abuse experiences decreased in frequency, but grew in severity, particularly for males.

Treatment of ambulatory hypertensives with nebivolol or hydrochlorothiazide alone and in combination. A randomized, double-blind, placebo-controlled, factorial-design trial.

This placebo-controlled multifactorial design trial assessed the antihypertensive efficacy of nebivolol, a novel cardioselective beta 1-blocker with vasodilating properties, and hydrochlorothiazide monotherapy and in combination. After a 4-week placebo period, 240 white patients with a mean daytime ambulatory blood pressure of > or = 90 mm Hg were randomized to receive either placebo, nebivolol (1, 5, or 10 mg), hydrochlorothiazide (12.5 or 25 mg), or one of the six possible combinations of nebivolol and hydrochlorothiazide for 12 weeks. A dose-related reduction in clinic and ambulatory blood pressure was demonstrated for each drug as monotherapy and for the two drugs in combination. Nebivolol, 5- and 10-mg doses, showed a larger effect than hydrochlorothiazide doses on clinic blood pressure and over the 24-h interval. Moreover, the combination doses had substantial antihypertensive effects that were sustained over the entire 24-h profile with a greater effect observed with the higher dose combinations. The reduction in ambulatory blood pressure was further substantiated by the reduction of blood pressure loads (% of BP > 140/90 mm Hg awake and > 120/80 mm Hg asleep) to as low as 11.5% with 10 mg of nebivolol combined with 25 mg of hydrochlorothiazide. Nebivolol and hydrochlorothiazide were well tolerated. We provided evidence that nebivolol, given as monotherapy or in combination with low dose of hydrochlorothiazide, is effective in reducing clinic and 24-h ambulatory blood pressure in patients with ambulatory hypertension. The results provided further evidence for the use of ambulatory blood pressure monitoring and factorial designs when investigating new antihypertensive agents.

[Acceptability of the Hemoccult test in general medical practice. Results of a pilot study]. / Acceptabilité du test Hémoccult en consultation de médecine générale. Résultats d'une étude pilote.

In view of preparing a controlled trial to assess the efficacy of screening for colorectal cancer by fecal occult blood testing in reducing cancer mortality, a pilot study was performed to evaluate the acceptability rate of the Hemoccult test in non selected subjects consulting in a general practice. 566 subjects aged 45 to 74 years from two small towns, Neuville-aux-Bois (Loiret) and Vicherey (Vosges) were included in the study. The screening test was proposed by GPs to 89.2% of their patients; of these, 5.6% refused the test and 9.4% did not return it. Of the tests carried out, 80.8% were performed spontaneously, and 19.2% after a recall letter. Acceptability depended neither on age or on sex. The patients' confidence in his GP was the most important acceptability factor (60%), followed by explanations the GP had provided, and ease of application. The results suggest that after receiving the correct information, a GP will succeed in prescribing the Hemoccult test to most high-risk subjects and that acceptability then proves excellent. Experience drawn from the pilot study has been very useful in conceiving the on-going controlled trial in Burgundy.