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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 chi2test. 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.

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.

Objective: To compare the efficacy and tolerability of the very-low-dose perindopril 2 mg/indapamide 0.625 mg (P/I) combination with the angiotensin II antagonist losartan 50 mg (L50) in the treatment of essential hypertension. Design and methods: This was a randomized, double-blind, parallel-group study. After a 2-week placebo period, all patients included were randomized to receive either P/I or L50 for a period of 12 weeks. Patients were 18 years of age or older and required a causal measurement of supine systolic blood pressure (sSBP) between 160 and 209 mm Hg and/or supine diastolic blood pressure (sDBP) between 95 and 114 mm Hg to be enrolled in the study. A 24-h ABPM (4 measurements per hour) was performed at week 0 and week 12. Statistical analyses: To demonstrate the non inferiority of the P/I combination on causal BP measurement (sSBP and/or sDBP), minimal equivalence was tested using a one-sided test procedure with a value of P < 0.025 (per-protocol analysis). Responder and normalization rates in the two groups were compared by a chi2 test and ABPM data by a Student t test. Safety data were analyzed on all randomized patients. A value of P < 0.05 was considered significant. Results: Among the 277 patients randomized, 232 took part in per-protocol analysis (122 P/I; 110 L50). Demographic, clinical, and laboratory characteristics were comparable between the two groups at inclusion. Blood-pressure-lowering effects (casual measurement) were equivalent in the two treatment groups. The average decreases in sSBP were 21.9 ± 13.3 mm Hg for P/I and 19.8 ± 16.1 mm Hg for L50 (CI: -5.95, +8) (non inferiority P = 0.0001), and in sDBP were 14.8 ± 8.5 mm Hg for P/I and 12.9 ± 8.6 mm Hg for L50 (CI: -4.07; +8) (non inferiority P = 0.029). Responder rate (BP < 140/90 mm Hg and/or a decrease in sDBP =10 mm Hg and/or a decrease in sSBP =20 mm Hg) was significantly higher in the P/I group (91.0%) than in the L50 group (81.8%), with P = 0.04. Normalization rate (sDBP < 90 mm Hg) was also significantly in favor of the P/I group (75.4% [P/I] versus 60.0% [L50], P = 0.012). The average nighttime SBP decrease (ABPM) analyzed in 137 patients (74 P/I and 63 L50) was significantly greater in the P/I group (-10.8 ± 10.8 mm Hg [P/I] versus -7.5 ± 11.7 mm Hg [L50], P = 0.045). The rate of patients with at least one emergent adverse event was similar in the two groups. Emergent adverse events related to treatment (with a frequency >0.7%) corresponding to one patient per group only included cough (4.1% in P/I), dizziness/giddiness (1.5% in L50), and asthenia (1.4% in P/I and 1.5% in L50). Conclusion: The very-low-dose perindopril 2 mg/indapamide 0.625 mg combination gives higher response and normalization rates than losartan 50 mg. This very-low-dose combination also provides a higher nocturnal decline in SBP (ABPM), which is a major significant predictor of cardiovascular complications. Both treatments were confirmed to have good and comparable tolerability.