Comparison of once and twice daily dosage forms of Pygeum africanum extract in patients with benign prostatic hyperplasia: a randomized, double-blind study, with long-term open label extension.

OBJECTIVES: To compare the efficacy and safety of Pygeum africanum extract, 50 mg twice daily and 100 mg once daily. METHODS: Patients with symptomatic benign prostatic hyperplasia (BPH) entered a 2-month randomized, parallel-group, double-blind, comparative phase (group A, 50 mg twice daily; group B, 100 mg once daily), followed by a 10-month, open phase (100 mg once daily). Main efficacy assessment parameters included International Prostate Symptom Score (IPSS), quality of life (QOL), and maximum urinary flow rate (Qmax). RESULTS: Two hundred nine patients completed the comparative phase in compliance with the protocol; 174 were included in the open phase. Both treatments had similar efficacy. IPSS (baseline 17 in both groups) improved by 38% in group A and 35% in group B. QOL improved by 28% in both groups. Qmax increased by 1.63 mL/s (16%) in group A and 2.02 mL/s (19%) in group B. After 12 months, the IPSS fell from 16 (baseline) to 9 (-46%). Half of the patients had an IPSS below 8. Mean Qmax increased by 1.65 mUs (15%). The safety profile was similar between groups and study phases. CONCLUSIONS: P. africanum extract at 50 mg twice daily and 100 mg once daily proved equally effective and safe at 2 months. Further improvements in efficacy with a satisfactory safety profile were documented after 12 months.

OESCLIM: summary of tolerability and safety.

INTRODUCTION: The benefits of transdermally administered estradiol have been well documented in a number of studies. OESCLIM is a new transdermal matrix system which has been developed with the objective of providing improved local skin tolerability and adhesion, whilst minimising hyperestrogenic effects. METHODS: Data relating to OESCLIM's tolerability and safety profile were reviewed. RESULTS: In a randomised, controlled comparative clinical trial, OESCLIM resulted in less than half as many application site reactions than Estraderm TTS (4.3 compared to 9.5%). In addition, the duration of reactions was significantly lower in the OESCLIM group. OESCLIM has been well tolerated in all clinical trials and was reported to have comparable estrogen-specific tolerability as Estraderm TTS. Low dose OESCLIM (25 microg/day) is associated with a reduction in hyperestrogenic side effects compared to higher doses. In a study of long term OESCLIM therapy, 79% of patients wished to continue therapy after 1 year, and in a follow up study 79.8% wished to continue at the end of the 3 year study. CONCLUSION: OESCLIM offers doctors an alternative to current transdermal therapy that is safe and effective and suitable for the majority of women. It has a better local tolerability and safety profile than Estraderm TTS and its safety has been proven in both short and long-term trials. The extensive range of OESCLIM doses available means doctors have a large flexibility and choice when it comes to deciding on an appropriate regimen including the option to initiate therapy at a low dose.

[Long-term effects of indapamide in left ventricular hypertrophy in patients with hypertension]. / Effets à long terme de l'indapamide sur l'hypertrophie ventriculaire gauche de l'hypertendu.

Left ventricular hypertrophy is a major and independent cardiovascular risk factor in hypertension. The effects of a diuretic, indapamide, on the regression of left ventricular hypertrophy were studied in a group of 9 patients with mild hypertension treated in an open therapeutic trial over a 12 month period. At the end of the trial, the left ventricular mass index decreased significantly from 172 +/- 11 to 147 +/- 11 g/m2 (p less than 0.001). Therefore, in contrast to the other diuretics which have been studied, indapamide seems able to induce regression of the left ventricular hypertrophy complicating hypertension.

Cardiovascular protective properties of indapamide.

Although indapamide has been used for many years as a first-line treatment of hypertension, it is only recently that some of its activities on the changes of the cardiovascular system, brought on by age and high blood pressure, have been studied. Indapamide appears to reduce blood pressure by a combined diuretic and direct vascular activity reducing vascular reactivity and total peripheral resistance. In addition, it has discrete effects on a number of interrelated systems that may protect the cardiovascular system. Indapamide reduces intracellular calcium levels, maintains magnesium ions, but reduces phosphate ions that may be involved in arterial rigidity. Circulating catecholamines remain unchanged but there is a reduction in normetanephrine, suggesting a reduction in sympathetic tone. It stimulates prostacyclin synthesis, increases levels of circulating prostacyclin, reduces platelet aggregation and stimulates the vasodilation elicited by endothelium-derived relaxing factor in the presence of bradykinin. In addition, it inhibits the formation of the vasoconstrictor prostanoid, thromboxane A2. The free radical scavenging activity of indapamide could also protect the vascular smooth muscle from the reperfusion injury of cerebral and myocardial ischemia. Indapamide induces a reduction in cerebral ischemia after carotid ligation. Unlike some other antihypertensives, it does not upset the high-density/low-density lipoprotein-cholesterol balance, reducing the possible risk of atherosclerosis. Moreover, the combination of binding to elastin and reduction in uptake of calcium and phosphate into the smooth muscle could be a mechanism for reducing arterial rigidity seen in the elderly and hypertensive patient. In hypertensive patients, these properties induce an improvement in arterial compliance, and in the long term a reduction in left ventricular hypertrophy. These pharmacologic and clinical results, together with a good antihypertensive efficacy and acceptability, suggest that indapamide may be a preferential agent in the long-term cardiovascular protection of the hypertensive patient.

Effects of indapamide on left ventricular mass and function in systemic hypertension with left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) is frequently associated with hypertension and constitutes a major cardiovascular risk factor, the reduction of which should be considered when initiating antihypertensive therapy. To assess the effects of indapamide on LVH, 18 hypertensive patients were included in the study (11 men and 7 women, age 53.6 +/- 2.9 years, mean +/- standard deviation) whose supine diastolic blood pressure was greater than 95 mm Hg without (n = 11) or with (n = 7:6 beta blockers, 1 calcium antagonist) antihypertensive therapy. All presented with LVH, echocardiographically defined by a left ventricular mass index greater than 110 g/m2. After a 2-week preinclusion period, all patients received indapamide, 2.5 mg/day, for a period of 6 months. Physical examination including blood pressure measurement was performed on selection (M-1/2), before (M0), and after 1 (M1), 3 (M3) and 6 (M6) months of indapamide treatment, and echocardiography was performed at M0 and M6. Quality of life was evaluated by means of questionnaires completed by the patient and the physician, and a visual analog scale was completed by the patient at M-1/2, M0 and M6. All clinical parameters remained stable during the 2-week preinclusion period. Indapamide administration induced a highly significant reduction in both supine systolic and diastolic blood pressures from 173.9 +/- 2.9/100.5 +/- 1.2 mm Hg at M0 to 150.9 +/- 1.9/90.5 +/- 1.3 mm Hg at M1 (p less than 0.001), and 145.0 +/- 1.7/86.0 +/- 1.5 mm Hg at M6 (p less than 0.001). Similar favorable effects were observed in the upright position.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute central and renal haemodynamic responses to tertatolol and propranolol in patients with arterial hypertension following head injury.

We compared the central and renal haemodynamic effects of tertatolol, a new non-cardioselective beta-adrenergic blocking drug without partial agonist activity, with those of an equipotent dosage of propranolol in two groups of 10 patients each with acute cerebral injury who had developed systemic hypertension. After tertatolol, 5 mg orally, mean arterial pressure was unchanged, heart rate decreased by 22% (P less than 0.01) and cardiac index by 24% (P less than 0.01), while renal blood flow remained unchanged (-5%, NS). After 160 mg propranolol orally, mean arterial pressure was unchanged, heart rate decreased by 12% (P less than 0.01), cardiac index by 16% (P less than 0.01) and renal blood flow by 17% (P less than 0.01). There was a moderate rise in norepinephrine levels after tertatolol only. Thus in this particular model of acute hypertension, tertatolol acted as a potent beta-blocking agent but differed from propranolol by preserving renal perfusion.

Tertatolol preserves renal perfusion in patients with arterial hypertension after head injury.

Tertatolol is a noncardioselective beta-adrenergic blocking agent without partial agonist activity. Its central and renal hemodynamic effects were compared to those of an equipotent dosage of propranolol in two groups of 10 patients each who developed arterial hypertension and a hyperdynamic circulatory state after head injury. After tertatolol, 5 mg orally, mean arterial blood pressure was unaffected, heart rate decreased by 22% (p less than 0.01) and cardiac index by 24% (p less than 0.01) while renal blood flow remained unchanged (-5%; not significant) so that the renal fraction of cardiac index was increased by 22% (p less than 0.05). After propranolol, 160 mg orally, mean arterial blood pressure was not modified, heart rate decreased by 12% (p less than 0.01), cardiac index by 16% (p less than 0.01) and renal blood flow by 17% (p less than 0.01) so that the renal fraction of cardiac index remained unchanged (-3%; not significant). Tertatolol is a potent beta-blocking agent comparable to propranolol apart from the fact that it preserves renal perfusion; this peculiar effect is related to a redistribution of the reduced cardiac output to the benefit of the kidney.