ACE-inhibition with perindopril in essential hypertensive patients with concomitant diseases. The Perindopril Therapeutic Safety Collaborative Research Group.

PURPOSE: Many hypertensive patients have other, usually long-term diseases. Antihypertensive therapy may interfere with these diseases and their therapies. In the present study, the possible interactions of the ACE-inhibitor perindopril with several of the most common long-term diseases was evaluated. PATIENTS AND METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, the effect of perindopril was evaluated in 490 patients with mild essential hypertension and any one of the following concomitant diseases: hyperlipidemia, type II diabetes mellitus, ischemic heart disease, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, chronic obstructive pulmonary disease, or degenerative joint disease treated with nonsteroidal anti-inflammatory drugs (NSAIDs). After a 3-week single-blind placebo run-in, the patients received either perindopril (4 mg/d) or matching placebo for 6 weeks. RESULTS: Blood pressure was effectively reduced by perindopril irrespective of the associated disease. The rate of spontaneously reported side effects was low. Treatment with perindopril was free from adverse interactions with the concomitant diseases and therapies. Moreover, favorable actions could be observed in patients with ischemic heart disease (reduction of maximal ST-segment depression during peak exercise and decrease in the number of angina attacks), in patients with proteinuria (decrease in albuminuria in patients with normal serum creatinine levels), and in patients with NSAID-treatment (increase in prostaglandin E2 concentration in gastric mucosa suggesting gastric cytoprotection). CONCLUSION: This trial shows that ACE-inhibition with perindopril represents a simple, safe, and effective short-term therapeutic option for the large proportion of patients with mild essential hypertension and concomitant diseases and therapies.

Therapeutic safety of perindopril in the treatment of mild hypertension with concomitant nephropathy.

Angiotensin-converting enzyme (ACE) inhibitors are well established antihypertensives. Their effect on kidney function, however, seems to depend on the pathophysiological mechanisms underlying the clinical symptoms. In one part of the Perindopril and Therapeutic Safety Study (PUTS) the effect of a 6-week treatment with placebo or 4 mg/d of perindopril (Coversum, CAS 82834-16-0) on kidney function and albuminuria was investigated in 56 hypertensives with concomitant nephropathy. The study was performed as multicenter, randomized, placebo-controlled, double-blind study. The results show that perindopril reduced blood pressure effectively. The responder rate determined as a fall in blood pressure at least about 10 mmHg in the perindopril group was 39% vs. 21% in the placebo group. All investigated parameters of kidney function like serum creatinine, creatinine clearance, urinary excretion of albumin and alpha 1-microglobulin remained unchanged during the study. In a subgroup of patients with isolated albuminuria ACE inhibition reduced significantly the urinary albumin excretion (perindopril: -292 +/- 205 mg/g creat. vs. placebo: +61 +/- 48 mg/g creat: p < 0.05). From this study it can be concluded that in hypertension with concomitant nephropathy, except renovascular hypertension and hypertension in renal transplant recipients, ACE inhibition by perindopril will not impair kidney function. In the early phase of nephropathy with isolated albuminuria and normal serum creatinine perindopril improves albuminuria and seems to be even of benefit for the kidney.

The effect of antihypertensive therapy on the course of renal failure.

The course and prognosis of chronic renal failure are much worse in hypertensive patients than in normotensive patients with otherwise similar basic disease. Therefore, antihypertensive measures with a combination of diuretics, beta-blockers, and vasodilators have clearly been shown to improve the progression of diabetic nephropathy. Treatment of hypertension with angiotensin-converting enzyme (ACE) inhibitors has also been shown to have a favorable effect on the prognosis of chronic renal failure. In the past few years, more knowledge about the pathogenesis of hypertension and the development of hypertension-induced organ damage has been followed by changing attitudes to antihypertensive therapy and the introduction of calcium antagonists for the treatment of hypertension, even in chronic renal failure. ACE inhibitors and calcium antagonists seem to be advantageous in the prognosis of chronic renal failure as they act on the humoral and trophogenic factors now known to be important in antihypertensive therapy.

[Fixed drug combination of ACE inhibitor plus diuretic. Results of an open multicenter study for the treatment of hypertension]. / Fixe Arzneimittelkombination von ACE-Hemmer plus Diuretikum. Ergebnisse einer offenen Multicenterstudie zur Hypertoniebehandlung.

An open multicenter trial involving 7,232 participating physicians, was performed to assess the anti-hypertensive efficacy and tolerance of a fixed combination of captopril and hydrochlorothiazide (Capozide) given once daily to 34,976 patients (mean age 58.5 +/- 11.4 years) with mild-to-moderate hypertension inadequately controlled by previous anti-hypertensive treatment. After 8 weeks, the response rate to a daily dose of Capozide 25 or 50 was 87.2%. Within this period, the mean systolic/diastolic blood pressure dropped from 175 +/- 16/103 +/- 5 mmHg to 150 +/- 13/88 +/- 7 mmHg (p less than 0.001). In 81% of the questionnaires, treatment with the combination was rated superior to the previous treatment; in only 5% was it considered inadequate. Side effects, for the most part mild, were reported by 7.4% of the patients. Treatment with Capozide was discontinued, or another form of treatment substituted in 12.9% of the cases.

Low-dose nitrendipine in mild hypertension: a double-blind, placebo-controlled, comparative study.

The objective of this study was to determine whether 10 mg of nitrendipine once daily is adequate for treatment of mild hypertension. The study was a randomized, double-blind, multicenter, and placebo-controlled group comparison over 8 weeks (a 2-week placebo-controlled washout phase followed by a 6-week treatment phase) with measurement of blood pressure, routine laboratory tests, compliance monitoring, and recording of side effects every 2 weeks. The study subjects were 141 outpatients with mild arterial hypertension and were given one 10-mg tablet of nitrendipine or placebo once daily. The end point used was reduction in diastolic blood pressure (DBP) by at least 10 mm Hg or to less than or equal to 90 mm Hg; the responder rate at the end of the treatment phase was determined. After 6 weeks of treatment, the mean reduction in DBP was 11.8 mm Hg under nitrendipine compared with 5 mm Hg under placebo. The responder rates were 73% (53 of 73 patients) in the nitrendipine group and 26% (18 of 68 patients) in the placebo group. This difference is statistically significant. Side effects were reported by a total of 14 patients (6 in the nitrendipine group, 8 in the placebo group). There was one dropout in each group. No changes in laboratory parameters were observed. In conclusion, nitrendipine is suitable for monotherapy of mild arterial hypertension in the dosage of 10 mg once daily used in this study.

[Membranoproliferative glomerulonephritis in non-Hodgkin's lymphoma nad myeloproliferative syndrome--a causal relationship?]. / Membranoproliferative Glomerulonephritis bei Non-Hodgkin-Lymphomen und myeloproliferativem Syndrom--eine kausale Beziehung?

A pathogenetic relationship is postulated for the development of membranoproliferative glomerulonephritis type I in non-Hodgkin's lymphoma (B-cell lymphoma of low-grade malignancy) and myeloproliferative syndrome, which we have observed in eight patients. This hypothesis is supported by the fact that chronic lymphatic leukaemia and immunocytoma are often associated with immunodysregulative phenomena, and by the immunohistological and ultrastructural findings in the kidney, especially the frequent electron-microscopic finding of cryoglobulins, which results in the membranoproliferative type of immune-complex glomerulonephritis, an expression of a disturbance in immune balance. The pathogenetic mechanism may involve cryoglobulins themselves as immune complexes; it is also possible that monoclonal cryoglobulins combine with an antigen to form immune complexes or lead to in situ formation of immune complexes. In addition, other immune complexes, for example with endogenous tumour-associated antigens and exogenous antigens (e.g. hepatitis antigens), may be involved in the pathogenesis.

[Effectiveness of pravastatin and bezafibrate in primary hypercholesterolemia]. / Wirksamkeit von Pravastatin und Bezafibrat bei primärer Hypercholesterinämie.

The efficacy and safety of pravastatin and bezafibrate (in retard form) were compared in a randomised double-blind trial comprising 96 patients (48 men, 48 women; mean age 52.5 [20-68] years) with primary hypercholesterolaemia types IIa and IIb. After four weeks' treatment 6 out of 38 patients (400 mg/d bezafibrate) and 27 out of 58 patients (20 mg/d pravastatin) reached a LDL cholesterol level of 190 mg/dl or less. In the other 31 patients of the pravastatin group the dose was raised to 40 mg/d. During the twelve-week course of pravastatin total cholesterol concentration fell from a mean of 364 +/- 75 mg/dl (initial value) to 281 +/- 61 mg/dl (P less than 0.01), while LDL-cholesterol fell from 288 +/- 81 mg/dl to 206 +/- 64 mg/dl (P less than 0.01) and triglyceride concentration from 168 +/- 83 mg/dl to 148 +/- 80 mg/dl (P less than 0.05). During the twelve-week course of treatment with 400 mg bezafibrate total cholesterol concentration fell from a mean of 363 +/- 91 mg/dl to 325 +/- 73 mg/dl (P less than 0.01), LDL-cholesterol level fell from 284 +/- 88 mg/dl to 242 +/- 70 mg/dl (P less than 0.01) and the triglyceride concentration from 173 +/- 91 mg/dl to 121 +/- 83 mg/dl (P less than 0.01). HDL cholesterol concentration rose by 9% in the bezafibrate group and by 8.4% in the pravastatin group (P less than 0.05). Except in the case of HDL-cholesterol, the falls were significantly different in the two treatment groups: pravastatin was superior to bezafibrate in terms of the reductions in both total and LDL-cholesterol (P less than 0.01 for each). However, bezafibrate produced a greater fall in serum triglycerides (P less than 0.05). No serious side effects were associated with either drug.

[Nonsurgical treatment of a massive macrohematuria following kidney biopsy]. / Nicht-operative Behandlung einer massiven Makrohämaturie nach Nierenbiopsie.

In the treatment of massive hematuria after renal biopsy, selective percutaneous vaso-occlusion with detachable balloons is an effective alternative to urological surgery, as demonstrated in the case of a 39-year-old man. A review of the literature, which records success rate of more than 90% in nonmalignant renal hemorrhage, confirms the therapeutic value of the various parenchyma-sparing embolization techniques.

Captopril and hydrochlorothiazide in the fixed combination multicenter trial.

The severe side effects uncommonly seen with captopril seem to be associated with high doses and/or compromised patients. A very flat dose-response curve in high dosages and the expectation of fewer side effects made us combine low-dose captopril with enhanced stimulation of the renin-angiotensin-aldosterone (RAA) system. Methods used were as follows: (a) In 43 patients (25 female, 18 male, age 45 +/- 10) with inadequate lowering of blood pressure or side effects due to therapy, we started a combination therapy with the fixed combination of captopril 25 mg + hydrochlorothiazide (HCTZ) 25 mg twice a day after a washout phase of 14 days. If blood pressure was not lowered satisfactorily, we increased the dosage to a fixed combination of 50 mg captopril + 25 mg HCTZ for 6 months. (b) In 12 patients (eight male, four female, age 47 +/- 7) an initial high-dose treatment of captopril (3 X 50-3 X 150 mg, mean = 325 +/- 87 mg/day in combination with small doses of diuretics) was changed to low-dose captopril (2 X 50 mg, mean = 96 +/- 14 mg/day; dose reduction: 70%!) in a fixed combination with 25 mg HCTZ in each tablet. Results obtained were as follows: (a) Initial blood pressure values of 189/106 +/- 28/7 mm Hg fell to 160/84 +/- 23/12 mm Hg after 2 weeks. Systolic pressure decreased further to 146 +/- 20 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

[Primary hypoaldosteronism and secondary pseudo-hypoaldosteronism]. / Primärer Hypoaldosteronismus und sekundärer Pseudo-Hypoaldosteronismus.

We observed a 23-year-old man with pronounced hyperkalemia (max. 6.8 mmol/l) and hyponatremia (min. 112 mmol/l), which had been existent for 3 years without complaint except a transitory psychorganic syndrome due to hyponatremia. Physical examination showed no abnormality except hypotension (blood pressure 100/70 mmHg). Renal function tests were normal. Fractional clearance of sodium was significantly increased (0.8%), whereas that of potassium was decreased (2.4%). Plasma renin activity was tripled and rose after furosemide. Plasma aldosterone was lowered and showed no rise after furosemide. Suppression of plasma renin and aldosterone by saline infusion was normal. Pressor dose of angiotensin II was increased (17,9 ng AT II/kg/min). Urinary excretion of aldosterone and its conjugates was below normal, and aldosterone precursors were within normal range. The findings were interpreted as selective primary hypoaldosteronism caused by corticosterone methyl oxidase defect type II. However, neither fludrocortisone (0.5 mg/day) nor sodium chloride (200 mmol/day) led to a normalization of sodium and potassium in plasma. Additional pseudohypoaldosteronism was thus assumed. Aldosterone infusion (3 mg in 1 h) decreased renal excretion of sodium; potassium excretion failed, however, to increase in contrast to its pattern in normal man. These findings resemble additional pseudohypo-aldosteronism of type II. After 8 weeks' application of additional 80 mmol sodium (as sodium bicarbonate) plasma sodium and potassium showed normal values under combined treatment with fludrocortisone (0.1 mg/day) and sodium bicarbonate (80 mmol/day). It is to be assumed that the patient suffers from a reduced aldosterone biosynthesis in the presence of an additional transitory secondary pseudohypoaldosteronism.

[Captopril in the treatment of essential hypertension (author's transl)]. / Captopril bei essentieller Hypertonie.

The antihypertensive effect of captopril was tested on 19 patients with essential hypertension, WHO grade I or II. In 11 patients blood pressure levels returned to normal over an observation period of 12 weeks at a dose of 3 C 50-150 mg daily (group A). In eight patients with grade II hypertension the absolute blood-pressure reduction was the same, but did not reach normal levels (group B). Although additional intake of propranolol, at a dose of 3 X 40 mg daily, achieved further reduction, normal pressures were still not attained. Initial blood pressure levels were higher and plasma-renin activity lower in patients of group B than of group A. There was a definite rise in plasma-renin activity with captopril, but corresponding to the suppression of plasma-renin in severe hypertension it was less. There was a fall in plasma-aldosterone levels, corresponding to a reduced angiotensin II level as a result of inhibition of the converting enzyme. The fall in plasma-aldosterone activity was less in severe hypertension, although there was the same inhibition of converting enzyme activity in both groups. Normochromic anaemia was noted in three patients, requiring further observation and explanation. No patient developed orthostatic hypotension or reflex tachycardia.