Antihypertensive efficacy and tolerability of low-dose perindopril/indapamide combination compared with losartan in the treatment of essential hypertension.

The aim of the study was to evaluate the antihypertensive efficacy and tolerability of the low-dose combination of the angiotensin-converting enzyme inhibitor perindopril 2 mg plus the diuretic indapamide 0.625 mg (P/I) compared with the angiotensin II antagonist losartan 50 mg (L50) in the treatment of essential hypertension. Patients (n = 277) were randomised, double-blind and allocated to receive either P/I or L50 once daily for a period of 12 weeks. Responder and normalisation rates in the two groups were compared by a chi 2 test. Ambulatory blood pressure monitoring results were compared using the one-tailed Student's t-test. Normalisation rates were significantly greater in the P/I group (76.0%) than in the L50 group (60.0%) (p = 0.009). Responder rates were significantly higher in the P/I group (91.7%) than in the L50 group (81.8%) (p = 0.025). The average blood pressure reductions were: in sSBP (P/I-L50 = -2.4 mmHg; CI: 6.2; 1.3) and sDBP (P/I-L50 = -2.0 mmHg; CI: -4.2; 0.2). The average night-time SBP decrease (ABPM) was significantly greater in the P/I group (p = 0.041). The tolerability was comparable between the two groups in terms of emergent adverse events related to treatment (12.4% for P/I patients and 8.4% for L50 patients). Laboratory evaluations did not show any significant variations. It was concluded the low-dose P/I combination had significantly higher responder and normalisation rates than L50. This study also confirmed the good tolerability of both treatments.

Incidence and predictive factors of cerebrovascular events in 8,846 elderly treated hypertensive patients during a 3-year follow-up: the PRESAGE study.

This epidemiological study was carried out as a 3-year follow-up project to assess the incidence of transient ischemic attacks (TIAs) and strokes; 8,846 treated hypertensive patients (mean BP, 149/84 mm Hg) aged 65 years or over (mean age, 73.7 +/- 6.3 years), devoid of symptoms of dementia and with documented vascular risk factors were recruited from January 1994 to August 1995, by 1,598 general practitioners in connection with 36 referral university neurology units throughout metropolitan France. Among these patients, 506 (5.7%) had at least one cerebrovascular event during the follow-up period: 309 (3.5%) experienced one or more isolated TIAs, and 197 (2.2%) had a stroke with or without a preceding TIA. A total of 510 TIAs were reported. The stroke subtypes were ischemia, hemorrhage, and unclassified in 70, 16, and 15% of the cases, respectively. The estimated annual stroke incidence was 7.42 per thousand. Of the 197 patients who developed strokes, 51 (26%) died. This case-fatality rate should be compared with the 4.5% mortality rate observed in the whole population during the study period. The 3 subgroups (with isolated TIAs, strokes, or no events during the study) were found to differ regarding age, sedentary lifestyle, past history of cardiovascular events, duration of hypertension, and evidence of complicated hypertension (univariate analysis). The factors identified as predictive of a stroke (multivariate analysis) were: the patient's age; sedentary lifestyle; pulse pressure (SBP-DBP); identification of TIA at baseline, and presence of arrhythmias.

Management of newly diagnosed non-insulin-dependent diabetes mellitus in the primary care setting: effects of 2 years of gliclazide treatment--the Diadem Study.

Five thousand five hundred seventy-two newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients (3,225 men and 2,347 women; mean age, 58.5 years) were recruited through the General Practitioners (GPs) network in France. All had persistent hyperglycemia after a preliminary 3-month period with dietary and life-style modification. Gliclazide (80 to 320 mg/d) was then prescribed as diabetic pharmacotherapy for 2 years. Additional therapy for hypertension and dyslipidemia was started if necessary. The aim of the study was mainly to determine the feasibility of a GP-directed protocol for the monitoring and treatment of newly diagnosed NIDDM patients, and to assess the effectiveness of diabetic therapy in this cohort. Diabetes was diagnosed in 78% of the cohort during routine screening. Among the women, 6.5% had a history of gestational diabetes. Eighteen percent of the patients had a parental history of diabetes, and the dominant maternal role in the genesis of NIDDM was confirmed. High blood pressure (Joint National Committee V criteria) was found at inclusion in 38.8% of the whole cohort. Hyperlipidemia was known in 44.6%. A history of stroke was present in 1.6% of the patients, and coronary heart disease (CHD) in 6.3%. These data support the relationship between the atherogenic state and development of NIDDM. Microalbuminuria defined as urinary albumin excretion (UAE) of at least 20 mg/L was found in 29.6% of the patients, and retinopathy in 9.8%. Among the included patients, 23% did not complete the study and were excluded from the efficacy analysis. Of these, 14% (808 patients) had only baseline evaluation data and 9% (499 patients) withdrew later. Comparison of mean baseline and final results in study completers uncovered a significant improvement in fasting blood glucose ([FBG] 182 +/- 48 v 137 +/- 40 mg/dL), post prandial blood glucose ([PPBG] 209 +/- 68 v 162 +/- 52 mg/dL), and hemoglobin A1c ([HbA1c] 8.7% +/- 2.5% v 7.3% +/- 2.0%). A slight improvement in total cholesterol (228 +/- 44 v 222 +/- 41 mg/dL), body mass index ([BMI] 28.5 +/- 4.7 v 27.9 +/- 4.5 kg/m2), and waist to hip ratio (0.99 +/- 0.1 v 0.98 +/- 0.1) was observed. There was a decrease in the percentage of patients with high blood pressure (38.5% v 30.7%). A mild increase in the prevalence of retinopathy (10.2% v 11.8%) was noted during the study, while the incidence of microalbuminuria remained unchanged (30.2% v 29.5%). In conclusion, the data indicate that the GPs involved in this study were able to successfully monitor and manage NIDDM patients in accordance with a standardized protocol. Gliclazide appeared to be an effective and well-tolerated treatment. The high prevalence of chronic diabetic complications at diagnosis emphasizes the delay encountered in reaching the diagnosis of NIDDM and the problems associated with this delay. In addition to the classic risk factors for NIDDM exhibited in this patient cohort, we have identified CHD and a maternal genetic component as further potential predicting factors.

Effects of a purified micronized flavonoid fraction on capillary filtration in diabetic patients.

The objective of the present study was to investigate the effects of a purified micronized flavonoid fraction (Daflon 500 mg) on the increased capillary filtration of albumin (CFA) which is an early change in the microcirculation of patients with diabetes. A placebo controlled trial lasting 30 to 42 days including two equal groups of 20 patients, following a 15-day initial placebo run-in phase. The CFA test employed consisted of injecting albumin labelled with technetium (99mTc) intravenously, applying a venous tourniquet to one arm, and counting the radioactivity on the ipselateral forearm using an external gamma camera. The disappearance of radioactivity was analysed by means of two parameters after the tourniquet had been released, i.e. albumin retention (AR) and the LF/HF index which indicates lymphatic function in interstitial protein clearance. All patients included exhibited an increase in these two indices before the initial placebo run-in phase and at the end of the run-in period. At the end of the treatment phase, AR had significantly decreased in the group treated by the flavonoid fraction (FF) by comparison with the placebo group, and had normalized in 65% of patients in the FF group, compared with 25% of patients in the placebo group (p = 0.010). The LF/HF index normalized in 55% of cases in the FF group, compared with no patients on placebo (p = 0.00001). This study suggests that the flavonoid fraction tested here can improve and even normalize capillary filtration of albumin in diabetic patients.

Capillary filtration and lymphatic resorption in diabetes. Application to the pharmacodynamic activity of Daflon 500 mg.

Microcirculatory disorders are often a complication of diabetes. They are associated with an increased capillary permeability which can be assessed by the Landis test using 99mTc-labelled albumin. Labelled albumin retention is measured by external detection (residual radioactivity after removal of venous tourniquet). The Fast Fourier Transform of the radioactivity disappearance graph reflects the lymphatic albumin resorption. Thirteen out-patients with diabetes from 1 to 19 years suffering from evident microcirculatory disorders were treated with a micronized flavonoid fraction: Daflon 500 mg (2 tablets per day) during a month. Antihypertensive and/or antidiabetic treatment were continued during the study if they were given before starting. A test was performed before, and at the end of the treatment. In 10 of the 13 patients, the test was carried out a third time 5.5 +/- 1.0 months later, after treatment withdrawal. Results were as follows: 1) labelled albumin retention was abnormal (greater than or equal to 8%) at the start and became normal in the patients and improved in 1 patient. After treatment withdrawal, the results of the third test were again abnormal, in the patients who had been normalized beforehand; 2) the initially abnormal lymphatic resorption became normal in six of the 13 patients at the end of the treatment and became abnormal again in all patients after treatment withdrawal. In a parallel group of 15 patients with abnormal test lymphatic fluctuations and not being treated with a vasculo-protector agent, the initially abnormal test remained abnormal 5 to 48 months later in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

A long term treatment with a venotropic drug. Results on efficacy and safety of Daflon 500 mg in chronic venous insufficiency.

UNLABELLED: Drugs for long term administration have to prove their efficacy and safety. Previously published double blind controlled studies (from single dose to two months treatment) have already demonstrated the phlebotropic activity of Daflon 500 mg in chronic venous insufficiency (CVI). The aim of the study was to investigate the safety of this agent during one year of continuous administration. Two-hundred and fifteen out-patients suffering from CVI received Daflon 500 mg, 2 tablets per day. Therapeutic activity was evaluated every 2 months on: 1) venous symptoms (functional discomfort, cramps, evening oedema) assessed by a 0 to 4 scale; 2) supramalleolar and calf circumferences; 3) overall assessment of efficacy (excellent, useful, nil). Acceptability was assessed by recording the side effects and measuring laboratory parameters. RESULTS: 170 patients completed the study. Functional symptoms were statistically significantly improved as shown by the following: functional discomfort: 0.55 +/- 0.06 vs 2.63 +/- 0.06, supra-malleolar circumference in cm: 22.5 +/- 0.2 vs 23.1 +/- 0.2, and calf circumference in cm: 34.7 +/- 0.3 vs 35.2 +/- 0.3. This improvement in the symptoms quickly appeared from the first control (M2) and reached about 50% of the total decrease. Overall assessment of efficacy was evaluated as follows: excellent = 58%, useful = 33%, nil = 9% of the cases. Laboratory parameters remained constant during the 12 months. Side effects were essentially gastralgia (n = 7). According to these results, it appears the efficacy and safety of Daflon 500 mg are corroborated even after a one year administration.