Antihypertensive activity of a new agent, indapamide: a double-blind study.

In a double-blind trail in 22 patients with mild to moderate essential hypertension, indapamide was compared with chlorathiazide and placebo. Dosage levels were set at 5 mg. indapamide and 500 mg. chlorothiazide daily, for 5 days out of 7, and patients were treated alternately, in random sequence, with each drug for a month over a 3-month period. Blood pressure readings and blood chemistry investigations were carried out before and after each treatment period and a careful history was kept of subjective symptoms and patients' tolerance of therapy. The results show that both active treatments produced drops in systolic and diastolic pressures, but were only statisically significant and different from placebo in the case of indapamide. Indapamide also produce much greater subjective improvement (74%) in patients with functional symptoms compared with chlorothiazide (15%). In an overall assessment, indapamide produced an excellent to good response to treatment in 57% of patients. Comparable responses for chlorotiazide and placebo were 25% and 20% respectivlely. Using patients as their own controls to compare the relative effectiveness of the three periods of treatment, indapamide was shown to be more effective than placebo in 65% of cases and more effective han chlorothiazide in 60%. Although patient tolerance of indapamide was slightly better, both drugs were well accepted and no significant changes from baseline levels were noted in any of the laboratory parameters investigated.

[Treatment of certain refractory arterial hypertensions with a monoamine oxidase inhibitor]. / Traitement de certaines hypertensions artérielles réfractaires par un inhibiteur de la mono-amino-oxydase.

Sixteen patients with refractory hypertension were treated with the monoamine oxidase inhibitor iproclozide at doses of 10 to 30 mg/day. Its addition to the previously prescribed antihypertensive therapy resulted in normalisation of blood pressure readings in two cases, significant improvement in seven cases and no change in four cases. Side effects due to iproclozide were relatively minor, the treatment having to be discontinued in three cases. Its association with alpha methyldopa or spironolactone did not lead to any untoward complications. Despite the success of other recently introduced drugs in refractory hypertension, this study shows that MAOI may be very useful in the management of this condition.

[Role of scintigraphy in the localization of pheochromocytoma]. / Apport de la scintigraphie à la localisation des phéochromocytomes.

Of the metabolic precursors of the catecholamines fixed by the adrenal medulla, 131I marked thyrosine was chosen as a radio-tracer. 6 positive results out of 11 pheochromocytomas confirmed at surgery were obtained in a series of 23 patients. This result is comparable with the results of arteriography but there are more false positives, reflecting the insecurity of this technique which is otherwise quite innocuous.

[Right adrenal recurrence of pheochromocytoma discovered 24 years after ablation of two ectopic pheochromocytomas]. / Nouvelle localisation surrénale droite d'un phéochromocytome découverte 24 ans après l'exérèse de deux phéochromocytomes ectopiques.

The classical localisation of chromaffin cell tumours is intra-adrenal. Ectopic or multiple tumours are not rare and are commonly observed in children. The authors report a case of ectopic pheochromocytoma with a double localisation in a 14 year old child (renal pedicle and right retropleural space), in which surgical ablation resulted in an immediate and sustained correction of the hypertension. Hypertension recurred 24 years later and a classical right adrenal pheochromocytoma was demonstrated by methyl-iodo-benzylguanidine (M.I.B.G.) scintigraphy and abdominal CT scan. Right adrenalectomy resulted in normalisation of the hypertension once again without antihypertensive therapy with a follow-up of three years. Regular follow-up is necessary after ablation of a pheochromocytoma, especially in children, even in the absence of a phacomatosis or multiple endocrine neoplastic syndromes.

[Non-invasive ambulatory measurement of arterial pressure. Recommendations of the measurement group of the French Society of Arterial Hypertension]. / Measure ambulatoire non invasive de la pression artérielle. Recommandations du groupe de la mesure de la Société française d'hypertension artérielle.

Ambulatory blood pressure monitoring is being widely used now that relatively simple, reliable and well-tolerated, non-invasive blood pressure measuring devices have become available. The following recommendations are only to help physicians to use this technique in their daily practice: only use homologated devices; ambulatory monitoring should be performed during normal, everyday activities; at least one measurement of blood pressure should be taken every 1/4 hour during the day time (7 h-22 h) and every 1/2 hour during the night (22 h-7 h); the arm must be absolutely still and relaxed during the measurement; the function of the measuring device should be checked when the patient is fitted up and when the device is removed; data processing should provide at least: all values of blood pressure and heart rate, and their times of measurement, the mean values of systolic end diastolic blood pressure and heart rate during the day and during the night, the maximal and minimal systolic and diastolic blood pressure values, a chronogramme of the values. Reasonable indications of ambulatory blood pressure monitoring include: elimination of the "white coat" effect: to confirm the diagnosis of borderline hypertension; to demonstrate inversion of diurnal rhythm in severe hypertension; to demonstrate episodic hyper or hypotension; to confirm certain cases of toxaemia of pregnancy. It is also justified in the evaluation of antihypertension therapy, especially in cases of suspected drug resistance.

[Coarctation of the abdominal aorta: diagnosis, pathogenesis, medical or surgical treatment. 7 cases]. / Coarctations de l'aorte abdominale: diagnostic, pathogénie, traitement médical ou chirurgical. Sept observations.

Seven cases of coarctation of the abdominal aorta are reported. The diagnosis, suggested by the presence of arterial hypertension associated with nonperception of the arterial pulse in the lower limbs and/or systolic murmur in the abdomen, is supported by non-invasive investigations, such as Döppler flowmetry of lower limb arteries and ultrasonography of the abdominal aorta. Arteriography, however, is mandatory because of frequently associated lesions of other arteries, notably renal and/or intestinal arteries. The type and location of these lesions are of prime importance to therapeutic decision. According to the results of the present study, surgery may not be required in all cases and may be replaced, in some very specific circumstances, by medical treatment. There is still disagreement concerning the congenital or acquired origin of this type of aortic coarctation and the mechanism of hypertension. The various theories put forward are discussed.

[Malignant pheochromocytoma. A case]. / Les phéochromocytomes malins. Une observation.

A case of malignant phaeochromocytoma is reported. The primary tumour was removed in 1970. Metastases were diagnosed in 1979 and management of the condition included antihypertensive treatment with alphamethylparatyrosine, antitumoral chemotherapy and surgical reduction of secreting tissue. In these rare tumours malignancy can only be confirmed by metastases, i.e. presence of chromaffin cells in loci where they are not usually found. Histology is of little value. High levels of catecholamine precursors or their metabolites in the urine may be a sign of malignancy, but some asymptomatic tumours are only revealed by metastases. Computerized tomography and radioisotope scanning with I131 metaiodobenzylguanidine are the best available methods to locate the lesions. In view of the small number of cases and of the unpredictable course (sometimes spread over many years) of malignant phaeochromocytomas, the effectiveness of treatments with alphamethylparatyrosine, chemotherapy and radiotherapy is difficult to evaluate.

Safety of the calcium antagonist lacidipine evaluated from a phase III-IV trial database.

OBJECTIVE: We reviewed the clinical safety profile of lacidipine with the help of the rather comprehensive datafile of the manufacturer. Although a number of prospective, randomly allocated trials under way at present are investigating the effects of treatment with calcium antagonists on cardiovascular morbidity and mortality, these results are not yet available. Therefore, the present approach may be useful. A fuller account of this work has been published in Blood Pressure. DESIGN: Since 1985,50 phase III-IV trials have been performed to investigate antihypertensive efficacy in patients with hypertension; 32 were controlled trials with comparison treatment and 18 were open studies of lacidipine treatment. Only data from trials completed before 1 January 1995 are presented here. SUBJECTS: In all, 16590 patients were treated with lacidipine; 13419 in open studies and 3171 in double-blind comparative trials. A total of 1810 patients were given active comparative treatment and 451 were given placebo. Altogether, 5124 person-years of data were obtained. MAIN OUTCOME MEASURES: Numbers of both fatal and non-fatal cardiovascular events were estimated. Efficacy (change in blood pressure and heart rate), adverse event rates and drop-out rates were compared for the different treatment regimens. RESULTS: In all trials, 2-6 mg lacidipine was effective in lowering blood pressure. In the controlled trials, systolic/diastolic blood pressure fell from 166/102 to 144/85 mmHg and the heart rate fell from 75.6 to 74.1 beats/min. The estimated event rate for a possible myocardial infarction in all studies was 5.46/1000 person-years; the fatal (all-cause) event rate was 5.27/1000 person-years and the estimated fatal cardiovascular event rate was 2.93/1000 person-years. There were 21 malignant events during treatment with lacidipine, for all studies yielding a crude incidence of 4.10/1000 person-years. In patients treated with lacidipine, the age-standardized (according to the world population) incidences were 1.49 (men) and 0.79/1000 person-years (women) compared with 2.74 (men) and 2.09/1000 person-years (women) in the European Community in 1990. The overall incidence in the comparative studies of one or more adverse events included 30.3% for lacidipine, 43.8% for other calcium antagonists, 18.7% for diuretics, 48.7% for beta-receptor blockers, 10.4% for angiotensin converting enzyme inhibitors and 15.7% for placebo. The adverse effects of lacidipine were, as expected, headaches, flushing, pedal oedema and palpitations. CONCLUSIONS: Lacidipine proved to be an effective and well tolerated drug in almost 19000 hypertensive patients. It displayed a reasonable adverse profile that was typical of a calcium antagonist of the dihydropyridine group. This analysis has two obvious limitations: (1) it is a retrospective analysis; and (2) the data were obtained from a large cohort of patients, but most were treated with lacidipine for a relatively short period of time. Although we found a lower fatal event rate than that reported by Collins et al., their meta-analysis included 10 times more person-years than our analysis, and therefore our event rate may be less accurate. Further prospective studies are under way at present to determine whether these drugs can produce reductions in atherosclerosis or in the incidence of cardiovascular disease.