[Effect of a fixed-dose combination of perindopril arginine/amlodipine on the level and variability of blood pressure according to its office visit-to-visit measurements and self-measurements at home: A subanalysis of the PREVOSHODSTVO (SUPERIORITY) program]. / Vliianie fiksirovannoi kombinatsii perindoprila arginin/amlodipin na uroven' i variabel'nost' arterial'nogo davleniia po dannym izmereniia na prieme u vracha i samokontrolia: cubanaliz programmy PREVOSKhODSTVO.

AIM: To study the effect of a fixed-dose combination of perindopril arginine/amlodipine (prestans) on the goal levels and variability of blood pressure (BP) according to its office visit-to-visit measurements and self-measurement (OVVM and SM) in a subgroup of 483 people from the population of the Russian observational SUPERIORITY program, most cases of whom are given the combination replacing the previously ineffective mono- and combination antihypertensive therapy (AHT). SUBJECTS AND METHODS: The subanalysis included data on 483 patients (34% men) aged 57.9±10.8 years with uncontrolled hypertension, who were both untreated and treated with antihypertensive mono- or combination therapy using a free or fixed-dose combination of 2-3 antihypertensive drugs and in whom the physicians decided to use prestans to correct AHT. The follow-up period was 24 weeks. RESULTS: At the end of the investigation, the patients received prestans in the following doses: 5/5 mg (34% of the patients), 10/5 mg (39.5%), 5/10 mg (3.9%), and 10/10 mg (22%). In the analyzed patient group, the baseline BP was 160.8±8.8/92.6±7.4 mm Hg and dropped to 125.9±7.9/77.8±5.0 mm Hg at 24 weeks (p<0.001). According to SM, the morning BP significantly decreased from 147.0±13.3/85.6±7.2 to 127.5±8.3/78,9±5.6 mm Hg at 24 weeks (p<0.001). The evening BP readings showed the similar trends. Target BP was achieved in 93 and 78% of the patients, as shown by OVVM and SM, respectively. According to SCM, the day-to-day variability of BP significantly decreased from 5.1±3.2/3.4±2.3 Hg mm at Visit 2 to 2.7±2/0/2,3±1/5 mm Hg at Visit 5 (p<0.001). CONCLUSION: The use of the fixed-dose combination of perindopril arginine/amlodipine in hypertensive patients just at the beginning of treatment, by switching from insufficiently effective mono- or combination AHT to the fixed-dose combination of perindopril arginine/amlodipine, is an effective way to optimize AHT in clinical practice, which lowers the BP level and variability, as evidenced by both OVVM and SM.

Cardiovascular protective role of a low-dose antihypertensive combination in obese Zucker rats.

OBJECTIVE: Obesity, non-insulin-dependent diabetes mellitus (NIDDM) and hypertension are leading causes associated with increased cardiovascular morbidity and mortality. In modern times, the combined first line antihypertensive therapy with at least two drugs with a different mechanism of action to achieve a better blood pressure control, is increasing in acceptance worldwide. The aim of the present study was to determine possible beneficial effects of the low-dose combination (LDC) of an angiotensin-converting enzyme (ACE) inhibitor, perindopril (PER), and the diuretic indapamide (IND), regarding myocardial and vessels protection in an animal model of hypertension, obesity and NIDDM, such as the obese Zucker rat (OZR), and control lean Zucker rats (LZR). DESIGN: Ten-week-old male OZR (fa/fa) and LZR (Fa/fa) were used in this study. OZR group (G1, n=8), OZR with LDC group (G2, n=8); LZR group (G3, n=8) and LZR with LDC group (G4, n=8). During 6 months, G2 and G4 received a daily dose of 1 mg/kg combination of 0.76 mg/kg PER + 0.24 mg/kg IND, (ratio of doses 0.32), by gavage, and G1 and G3 received an equal volume of vehicle throughout the experiment. In order to evaluate cardiac dimensions and left ventricular mass (LVM) transthoracic echocardiograms were performed, at baseline and at the end of the experiment. Urine and blood samples for biochemical determination were obtained. After 6 months of treatment all rats were sacrificed, hearts were harvested for light microscopy (LM), high-resolution light microscopy (HRLM), immunohistochemistry including monoclonal antibodies against transforming growth factor beta (TGFbeta1) and anti-collagen type I (COL I) and type III (COL III) and electron microscopy (EM) studies. RESULTS: At the end of the study OZR treated with LDC presented: (1) lower blood pressure (128.9 +/- 4 versus 150.3 +/- 3.6 mmHg, P< 0.05); (2) smaller cardiac dimensions (P< 0.01); (3) lower LVM/100 g body weight (0.17 +/- 0.02 versus 0.30 +/- 0.05, P< 0.01); (4) higher fractional shortening (34.5 +/- 3.2 versus 23.3 +/- 5.9%, P< 0.01) than OZR untreated. Moreover, OZR that received LDC showed higher: (1) myocyte density (48 +/- 1.5 versus 20 +/- 2.5 myocytes/area, P< 0.01); (2) capillary density (30.5 +/- 3.1 versus 9.5 +/- 1.6 capillaries/area, P<0.01); (3) myofilament thickness (12.05 +/- 0.27 versus 9.83 +/- 0.39 nm, P<0.01); and lower amounts of: (1) TGFbeta1 in myocytes (P< 0.01), interstitium (P< 0.01) and vessel wall (P< 0.05); (2) COL I and COL III (P< 0.01), and COL I /COL III ratio (P< 0.01), compared with untreated OZR. Finally, OZR-treated with LDC showed not only unsubstantial modification in carbohydrate and lipid metabolism when compared with untreated OZR, but also an improvement in insulin/glucose ratio (P< 0.05). CONCLUSION: These results suggest that LDC of PER + IND can control cardiovascular damage in OZR providing an additional help in the metabolic scenario likewise.

ACE inhibitors in heart failure--switching from enalapril to perindopril.

Although ACE inhibitors have demonstrated their beneficial effects in heart failure, whether different agents may induce different benefits remains unclear. We designed an open, sequential, prospective study switching heart failure patients receiving enalapril to perindopril which has been reported to be longer acting and better tolerated. The objective of the study was to find out if clinical and functional status could be further improved by changing from enalapril 30 mg daily to a perindopril 4 mg daily. Assessments of clinical status, echocardiography and nuclear ventriculography were performed at baseline under enalapril (30 mg mean dose (b.i.d.)), then 6 and 12 months after the switch to perindopril (4 mg/day mean dose). Thirty-one patients were included (90% men, aged 56.5 +/- 11.8 years, mean radionuclide left ventricular (LV) ejection fraction 22.4 +/- 8.5 %). After 6 months of treatment, NYHA functional class was significantly improved; the percentage of patients in class I increased to 57% after perindopril versus 20% at baseline (p < 0.001), and 50% of the total study population gained at least one NYHA class. After 12 months of treatment, 80% of the patients were in NYHA class I. Blood pressure decreased significantly with a good tolerance at 6 months and then remained stable. After 12 months of treatment, significant reductions of LV end-diastolic diameter (61.4 +/- 5.3 vs. 64.5 +/- 6.5 mm; p = 0.001) and LV mass index (143.3 +/- 21.5 vs. 164.2 +/- 40.2 g/m2; p < 0.001) were observed, reflecting a positive effect on the LV remodelling process. Despite some limitations, because it is of an open-label design with a small number of patients, our study found significant differences in clinical and objective parameters in heart failure patients switched from enalapril to perindopril. The prognostic significance of these findings remains to be investigated.

[Early prevention of experimental left ventricular hypertrophy in experimental hypertension and angiotensin II levels]. / Prevención precoz de hipertrofia ventricular izquierda en la hipertensión experimental y concentraciones de angiotensina II.

INTRODUCTION: Angiotensin II levels can be partially inhibited during chronic administration of angiotensin converting enzyme (ACE) inhibitors, limiting from a clinical point of view its efficacy in the treatment of hypertension. There are few studies relating ACE activity directly with early prevention of left ventricular hypertrophy (LVH) in systemic hypertension during the administration of an ACE inhibitor (ACEI). AIM: To evaluate the effects of early ACE inhibition with perindopril on the development of hypertension, LVH and levels of angiotensin II (Ang II) in plasma as well as in LV in the rat Goldblatt model (Gb; 2 kidneys-1 clip), 2 weeks after surgery. RESULTS: Systolic blood pressure and relative LV mass increased by 42% and 20% respectively, in the Gb group (p < 0.001). Plasma and LV ACE activities were significantly higher in the Gb rats compared with the control rats. Plasma and LV Ang II levels also increased by 129% and 800%, respectively. Perindorpil prevented hypertension and LVH development by inhibiting plasma ACE (and also LV ACE), and also circulation Ang II in plasma and in the LV. CONCLUSIONS: In this experimental model of hypertensive LVH, there is an early activation of plasma and cardiac ACE. Early administration of an ACE inhibitor prevents the development of hypertension and LVH by inhibiting the increases of plasma and LV Ang II.