indapamide--perindopril-drug-combination and Hypertension

Much of the chronic care of patients with type 2 diabetes mellitus and hypertension involves the prevention of diabetic complications. Renin-angiotensin system inhibitors are recommended as first-line therapies because of their nephroprotective properties. Their combination with metabolically neutral diuretics is recommended to reduce blood pressure, morbidity and mortality. Our objective was to review the mechanisms by which the combination of the angiotensin-converting enzyme inhibitor, perindopril, and metabolically neutral thiazide-like diuretic, indapamide, targets the pathways involved in microvascular and macrovascular diabetic complications.. For this narrative review, extensive literature searches were performed using PubMed/Medline. Articles published in English describing clinical trials and mechanism of action studies that were relevant to the treatment of patients with perindopril and/or indapamide were included.. Perindopril/indapamide treatment has been shown to reduce blood pressure and to have significant beneficial effects on arterial distensibility, kidney structure and function, and endothelial function. Recent data also suggests that perindopril may reduce the deleterious accumulation of advanced glycation end products in diabetic tissue. In the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation diabetes trial, perindopril/indapamide treatment significantly reduced the relative risk of microvascular and macrovascular events by 9%, cardiovascular mortality by 18%, and all-cause mortality by 14%. Interestingly, 6 years after the end of the double-blind period, follow-up data showed that the beneficial effects on mortality continued to be significant even though differences in blood pressure and glycated hemoglobin levels had not been significant for several years. Together this data suggests that treatment with perindopril/indapamide has microvascular and macrovascular effects that extend beyond blood pressure lowering and that this treatment might confer a long-lasting beneficial vascular legacy.. Moving forward, understanding the pathophysiological bases of the effects that extend beyond those of blood pressure control will help us differentiate between anti-hypertensive choices.

Topics: Antihypertensive Agents; Blood Circulation; Diabetes Mellitus, Type 2; Drug Combinations; Humans; Hypertension; Indapamide; Perindopril

More than 50 % of hypertensive patients have lipid disorders, and one-third of hypertensive patients have impaired glucose metabolism. Owing to the high prevalence of metabolic risk factors and/or comorbidities, antihypertensives with favorable or neutral metabolic effects are preferred. Based on the available evidence, diuretics and β-blockers are heterogeneous regarding their metabolic effects.. The aim of ACES (Antihypertensive Combinations' Long Term Efficacy Comparing Study) was to compare the efficacy and metabolic effects of a carvedilol/indapamide free combination, a fixed-dose combination of perindopril/amlodipine, and a fixed combination of perindopril/indapamide in everyday practice.. This study was a 6-month, multi-center, prospective, observational, non-interventional, open-label clinical study. The data of 9124 outpatients (4898 female, 4226 male; mean age 61.7 ± 11.7 years) with mild, moderate, or severe essential (primary) hypertension with one or more metabolic risk factors were subjected to statistical analysis. At visits one (day 1), three (month 3), and four (month 6), the following metabolic parameters were monitored: fasting blood glucose, glycosylated hemoglobin, estimated glomerular filtration rate, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, and serum potassium, sodium, creatinine, and uric acid levels. A total of 3888 patients took perindopril/amlodipine, while 2992 took perindopril/indapamide, and 2244 took a combination of carvedilol/indapamide. Statistical analysis was carried out using the one-paired t test and the Chi square test; the two-sided level of significance was set at 0.05.. The observed changes in the main metabolic parameters were favorable and similar in all therapeutic groups: fasting blood glucose decreased by 5.5-5.5-5.5 %, total cholesterol by 9.0-10.2-9.9 %, and triglycerides by 12.7-15.4-13.8 % (respectively in perindopril/amlodipine, perindopril/indapamide and carvedilol/indapamide groups).. Based on our findings, we conclude that the metabolic profile of indapamide is very similar to the metabolically neutral and well-documented metabolic profiles of the calcium-channel blocker amlodipine and the vasodilator β-blocker carvedilol and that all the combinations studied had similar beneficial effects on the main metabolic parameters. The favorable changes of metabolic parameters are because of the discontinuation of active substances (e.g., conventional thiazides, second-generation β-blockers) used in the previous therapy, which were associated with unfavorable metabolic effects, and to the increase in the ratio of administered lipid-lowering drugs and oral antidiabetic drugs.

Topics: Adult; Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Carbazoles; Carvedilol; Diuretics; Drug Combinations; Essential Hypertension; Female; Humans; Hypertension; Indapamide; Lipoproteins, LDL; Male; Middle Aged; Perindopril; Propanolamines; Prospective Studies; Risk Factors

Most recent meta-analyses of morbidity-mortality risk hazards brought about by the presence of diabetes as compared with non-diabetics underline the dominant risk of renal disease and cardiovascular outcomes and the relevance of blood glucose, blood pressure (BP) and cholesterol levels. The translation of this reality into therapeutic guidelines always requires interventional evidence. Evidence for combined approaches in controlling for BP and blood glucose was provided by Action in Diabetes and Vascular disease: PreterAx and DiamicroN-MR Controlled Evaluation (ADVANCE), conducted in over 11 000 subjects from 20 countries. Reduction in systolic BP by 7.1 mm Hg, in diastolic BP by 2.9 mm Hg and in glycated haemoglobin A1c by 0.61% points in the combined routine BP lowering and intensive blood glucose-control group after an average 4.3 years of follow-up resulted in a relative risk reduction of 28% in renal events, 24% in cardiovascular death and 18% in all-cause mortality. While other major intervention trials performed in similar populations with analogous goals did not achieve the same level of positive therapeutic evidence and even pointed to some risk of intensified treatment of type 2 diabetes, all three major studies [Action to Control Cardiovascular Risk in Diabetes (ACCORD), Veterans Affairs Diabetes Trial (VADT) and ADVANCE] showed significant reduction in renal events, the major risk in type 2 diabetes. The divergence for other outcomes underlines the importance of considering specific therapeutic approaches for glucose control and prudent targets for BP. The current target values for glycated haemoglobin of 6.5-7% and for BP of 130/80 mmHg appear safe and beneficial. The potential long-term benefit, particularly that of initial tight blood glucose control, suggested by recent post-trial evidence is currently being evaluated in the ADVANCE-ON study.

Topics: Antihypertensive Agents; Biomarkers; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Drug Combinations; Glycated Hemoglobin; Humans; Hypertension; Hypoglycemic Agents; Incidence; Indapamide; Kidney Failure, Chronic; Multicenter Studies as Topic; Perindopril; Randomized Controlled Trials as Topic; Risk Factors

Treatment of hypertension is fundamental for the prevention of cardiovascular events and mortality. This review focuses on the specific benefits of the ACE inhibitor perindopril.. A systematic literature search is undertaken for supporting the pharmacological proprieties and clinical efficacy of perindopril in the treatment of hypertension. Good tissue penetration, strong affinity for ACE and a long duration of action support the dose-dependent blood pressure lowering efficacy. Perindopril in combination with amlodipine significantly reduced total and cardiovascular mortality as compared to atenolol/diuretic in large-scale clinical trials of hypertensive patients. A greater reduction in blood pressure variability, central blood pressure and specific vascular protective proprieties of perindopril (improvement in arterial stiffness and endothelial function) might explain these results. Cardiovascular prevention with perindopril, in combination with indapamide, has been also shown in the elderly and patients with diabetes, cardio- and cerebrovascular diseases.. Perindopril is effective and safe for blood pressure control with a dose-dependent effect. Combination therapy with indapamide or amlodipine reduces cardiovascular events and mortality in hypertensive patients. Pharmacological proprieties and results of clinical trials support the choice of perindopril as an appropriate treatment for hypertensive patients.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Dose-Response Relationship, Drug; Drug Combinations; Humans; Hypertension; Indapamide; Perindopril

Despite the widespread notion that controlling hypertension is essential to improve cardiovascular outcome, uncontrolled hypertension rates remain high. Fixed-dose combinations are used routinely to reduce the impact of hypertension. Treatment with fixed-combination perindopril/indapamide, for example, at the currently approved doses (perindopril 2 mg/indapamide 0.625 mg [Per2/Ind0.625] and perindopril 4 mg/indapamide 1.25 mg [Per4/Ind1.25]), reduces blood pressure, end-organ damage, and cardiovascular morbidity and mortality in a wide range of hypertensive patients.. This article reviews three published randomised trials that evaluated the efficacy and safety of the highest dose of perindopril/indapamide (perindopril 8 mg/indapamide 2.5 mg [Per8/Ind2.5]) in blood pressure lowering and end-organ protection studies.. In the first (dose-finding) study, incremental reductions in SBP/DBP were observed with each dose doubling. After 8 weeks of treatment, decreases in supine SBP/DBP were statistically significant compared to placebo for all three doses, with incremental and progressive reductions with each dose doubling: ranging from SBP/DBP respectively -14/-9 mmHg for Per2/Ind0.625 to -23/-15 mmHg for Per8/Ind2.5 compared to -5/-5 mmHg for placebo. In the PICXEL and PREMIER trials, SBP/DBP decreases of 16.3/8.1 mmHg (p < 0.0001) and 2.5/2.6 mmHg, respectively, were noted when Per4/Ind1.25 was doubled to Per8/Ind2.5 (decreases from 167.7/101.7 to 151.4/93.6 in PICXEL and from 154.9/92.1 to 152.4/89.5 in PREMIER, respectively). As a consequence more patients had normalised blood pressure (22% and 17%), more patients responded to treatment (68% and 45%), and 29% and 10% of non-responders became responders, in PICXEL and PREMIER, respectively. Additional end-organ benefits were also noted with Per8/Ind2.5. In PICXEL, significant decreases from baseline in left ventricular mass were noted with all three doses, with a 17.5 g/m(2) decrease from baseline in patients whose maximum dose was Per8/Ind2.5 (from 148.5 g/m(2) +/- 39.5 (mean +/- SD) to 131 g/m(2); p < 0.0001). In PREMIER, changes in albumin excretion rate were also noted with all three doses, with a 45% reduction from baseline in patients whose maximum dose was Per8/Ind2.5 (p < 0.0001). When safety data, including potassium levels, were analysed, the increase in dose to Per8/Ind2.5 did not have a notable impact on the safety profile of perindopril/indapamide.. Based on data available from an evaluation of three randomised clinical trials, fixed-combination Per8/Ind2.5 provided a significant, incremental reduction in blood pressure as well as cardiac and renal end-organ protection while remaining safe and well-tolerated.

Topics: Antihypertensive Agents; Blood Pressure; Cytoprotection; Dose-Response Relationship, Drug; Drug Combinations; Humans; Hypertension; Indapamide; Kidney; Kidney Diseases; Perindopril; Randomized Controlled Trials as Topic; Titrimetry; Treatment Outcome

Brachial pulse pressure (PP) is now a well-established cardiovascular risk factor. Central rather than peripheral PP should be measured to determine the 'true' haemodynamic effects of antihypertensive agents on target organs. Peripheral PP, measured at the brachial artery, does not reflect central PP (either carotid or ascending aorta), because their determinants are different and pathophysiological conditions and drugs may change central PP without changing peripheral PP. Central PP (i.e. carotid artery or ascending aorta) has shown an independent predictive value for all-cause mortality in patients with end-stage renal disease and in the hypertensive patients of the CAFE study. Antihypertensive treatment has repeatedly demonstrated its ability to prevent cardiovascular events. Whether the effect on cardiovascular events in clinical trials comparing two pharmacological classes or two therapeutic strategies is, at least partly, the result of differential effects on PP remains to be demonstrated. It is therefore of major importance to determine which therapeutic strategies may differentially lower central PP, and in turn reduce cardiovascular events. In clinical practice, lowering PP is often a difficult task, particularly in diabetic hypertensive individuals. In the PARADIS study, we aimed to determine, in a population of hypertensive patients with both type 2 diabetes and PP greater than 60 mmHg, which clinical characteristics predict the fall in PP on treatment and a reduction in cardiovascular events. The reinforcement of therapeutic measures, including a fixed low-dose perindopril/indapamide combination, made possible the effective lowering of PP and cardiovascular events in type 2 diabetic hypertensive patients, under conditions of usual care by general practitioners and specialists.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Clinical Trials as Topic; Diuretics; Drug Combinations; Humans; Hypertension; Indapamide; Perindopril

Type 2 diabetes mellitus (T2DM) is often accompanied by high blood pressure (BP) and the clustering of several cardiovascular risk factors, and is the most frequent cause of end-stage renal disease. The stages of development of overt nephropathy in T2DM patients range from an initial alteration in renal function with an increased GFR, followed by the development of microalbuminuria and macroalbuminuria or proteinuria, featuring an established diabetic nephropathy, which eventually progresses to end-stage renal disease. Early intervention is needed to prevent the development of diabetic nephropathy and requires effective control of the different risk factors, and in particular high BP. In the initial stages of the disease, strict BP control is crucial to prevent the development of initial renal and vascular damage. Adequate BP control is particularly difficult in T2DM patients and in most cases requires the use of combination therapy. Preterax, a fixed-dose combination of perindopril 2 mg and indapamide 0.625 mg, allows BP to be significantly reduced compared with conventional strategies; this combination can be uptitrated to BiPreterax when further BP control is needed. In the PREMIER study performed in T2DM over 12 months, the perindopril/indapamide combination brought about, in addition to excellent BP control, a significant reduction in urinary albumin excretion, compared with monotherapy with enalapril. In more advanced degrees of renal damage, higher doses of the fixed combination have to be considered. The pharmacological basis of the renoprotective effect of perindopril/indapamide is the demonstration that this combination prevented nephropathy as well as proteinuria in obese Zucker rats, independently of BP control. Strict BP control from the initial stages of nephropathy together with inhibition of the renin-angiotensin system is mandatory to prevent albuminuria. The fixed combination of perindopril/indapamide can greatly help clinicians in achieving the above goals, using Preterax in the early and BiPreterax in the late stages of nephropathy.

Topics: Albuminuria; Antihypertensive Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Combinations; Humans; Hypertension; Indapamide; Perindopril

Pharmacological treatment of hypertension represents a cost-effective way of preventing cardiovascular and renal complications. To benefit maximally from antihypertensive treatment, blood pressure should be brought to below 140/90 mmHg in every hypertensive patient, and even lower (< 130/80 mmHg) if diabetes or renal disease co-exists. Such targets cannot usually be reached using monotherapies. This is especially true in patients who present with a high cardiovascular risk. The co-administration of two agents acting by different mechanisms considerably increases the blood pressure control rate. Such combinations are not only efficacious, but are also well tolerated, and some fixed low-dose combinations even have a placebo-like tolerability. This is the case for the preparation containing the angiotensin-converting enzyme inhibitor perindopril (2 mg) and the diuretic indapamide (0.625 mg), a fixed low-dose combination that has been shown in controlled trials to be more effective than monotherapies in reducing albuminuria, regressing cardiac hypertrophy and improving the stiffness of large arteries. Using this combination to initiate antihypertensive therapy has been shown in a double-blind trial (Strategies of Treatment in Hypertension: Evaluation; STRATHE) to normalize blood pressure (< 140/90 mmHg) in significantly more patients (62%) than a sequential monotherapy approach based on atenolol, losartan and amlodipine (49%) and a stepped-care strategy based on valsartan and hydrochlorothiazide (47%), with no difference between the three arm groups in terms of tolerability. An ongoing randomized trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; ADVANCE) is a study with a 2 x 2 factorial design assessing the effects of the fixed-dose perindopril-indapamide combination and of the intensive gliclazide modified release-based glucose control regimen in type 2 diabetic patients, with or without hypertension. A total of 11 140 patients were randomly selected. Within the first 6 weeks of treatment (run-in phase), the perindopril-indapamide combination lowered blood pressure from 145/81 +/- 22/11 mmHg (mean +/- SD) to 137/78 +/- 20/10 mmHg. Fixed-dose combinations are becoming more and more popular for the management of hypertension, and are even proposed by hypertension guidelines as a first-line option to treat hypertensive patients.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Diuretics; Drug Combinations; Humans; Hypertension; Indapamide; Perindopril; Vascular Diseases

Weight loss is strongly recommended for overweight and obese adults with type 2 diabetes. Unintentional weight loss is associated with increased risk of all-cause mortality, but few studies have examined its association with cardiovascular outcomes in patients with diabetes.. To evaluate 2-year weight change and subsequent risk of cardiovascular events and mortality in established type 2 diabetes.. The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation was an international, multisite 2×2 factorial trial of intensive glucose control and blood pressure control. We examined 5 categories of 2-year weight change: >10% loss, 4% to 10% loss, stable (±<4%), 4% to 10% gain, and >10% gain. We used Cox regression with follow-up time starting at 2 years, adjusting for intervention arm, demographics, cardiovascular risk factors, and diabetes medication use from the 2-year visit.. Among 10 081 participants with valid weight measurements, average age was 66 years. By the 2-year examination, 4.3% had >10% weight loss, 18.4% had 4% to 10% weight loss, and 5.3% had >10% weight gain. Over the following 3 years of the trial, >10% weight loss was strongly associated with major macrovascular events (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.26-2.44), cardiovascular mortality (HR, 2.76; 95% CI, 1.87-4.09), all-cause mortality (HR, 2.79; 95% CI, 2.10-3.71), but not major microvascular events (HR, 0.91; 95% CI, 0.61-1.36), compared with stable weight. There was no evidence of effect modification by baseline body mass index, age, or type of diabetes medication.. In the absence of substantial lifestyle changes, weight loss may be a warning sign of poor health meriting further workup in patients with type 2 diabetes.

Topics: Adult; Aged; Body-Weight Trajectory; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Combinations; Female; Follow-Up Studies; Gliclazide; Humans; Hypertension; Indapamide; Life Style; Male; Middle Aged; Obesity; Overweight; Perindopril; Risk Factors; Weight Gain; Weight Loss

The relationship between blood pressure (BP) and cerebral blood flow (CBF) is not fully understood. This study evaluated the impact of a perindopril arginine/indapamide (Pa/I) single-pill combination (SPC) on CBF in middle-aged patients.. A total of 22 treatment-naïve patients with essential hypertension and at least one hypertension-mediated organ damage and 41 healthy controls were enrolled. At baseline, all participants underwent brain magnetic resonance imaging (MRI); patients with hypertension underwent an additional MRI at end of follow-up. Arterial spin labeling (ASL) was used to calculate CBF in the frontal lobe cortical plate. Patients with hypertension received once-daily Pa/I 5 mg/1.25 mg SPC, which could be increased to Pa/I 10 mg/2.5 mg at 2 weeks if necessary. Patients with hypertension underwent 24-h ambulatory BP monitoring (ABPM) at baseline and end of follow-up.. Mean baseline BP values were 146.2/93.1 and 119.1/76.1 mmHg in the hypertension and control groups, respectively. Patients with hypertension had significantly (p < 0.001) lower CBF in the cortical plate of both left (36.2 ± 8.3 vs. 45.3 ± 3.5 ml/100 g/min) and right (37.9 ± 7.9 vs. 45.8 ± 3.2 ml/100 g/min) frontal lobes compared to normotensive controls. At the end of follow-up, there was a statistically significant (p < 0.001) increase in CBF in the cortical plate of both left (from 36.2 ± 8.3 to 47.5 ± 9.8 ml/100 g/min) and right frontal lobes (from 37.9 ± 7.9 to 47.4 ± 10.1 ml/100 g/min) compared to baseline. No significant difference was found between end of follow-up CBF levels in frontal lobes of patients with hypertension and those of healthy controls at baseline. Office BP decreased by 24.2/15.5 mmHg and 24-h ABPM from 145.5/95.3 to 120.8/79.3 mmHg.. In middle-aged, treatment-naïve patients with hypertension, Pa/I SPC was associated with increased CBF in the cortical plate of the frontal lobes, which achieved levels of normotensive controls. The increase in CBF had no clear association with observed BP changes.. ISRCTN67799751.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cerebrovascular Circulation; Drug Combinations; Essential Hypertension; Female; Humans; Hypertension; Indapamide; Magnetic Resonance Imaging; Male; Middle Aged; Perindopril

Most antihypertensive drugs used in monotherapy or in combination therapy reduce the left ventricular mass index (LVMI). However, little is known about the effects on LVMI of a triple fixed-dose combination (TFC) therapy, containing in a single pill an angiotensin-converting enzyme inhibitor (ACEI), a diuretic and a calcium channel blocker (CCB).. In this prospective open-label study, 92 patients with essential hypertension were randomized to treatment with a TFC of perindopril/indapamide/amlodipine at different doses or a triple free combination therapy (FCT) including ACEI/diuretic/CCB. Office blood pressure (BP) measurement, 24 h-ambulatory BP monitoring and echocardiography were performed at baseline and during a 14-month follow-up. The BP variability (BPV) over 24 h was calculated as ± standard deviation of the daytime systolic BP. Differences between office and monitored BP and LVMI were evaluated by ANOVA for repeated measures.. A significant BP-lowering effect was observed for both treatments. At follow-up, BPV was reduced in both the treatment groups vs. the baseline (14.0±1.5 vs. 17.0±1.8 and 16.2±2.1 vs. 17.6±2.3, respectively), but it was lower in the TFC vs. the FCT group (14.0±1.5 vs. 16.1±2.2, P < 0.05). LVMI was lower in both the treatment groups, but the change was greater for TFC vs. FCT (-8.3±4.9% vs. -2.0 ±2.1%, P < 0.0001). Left ventricular hypertrophy (LVH) regression was greater in the TFC vs. the FCT group (43.5% vs. 30.4%, P < 0.05).. Independently of BP values achieved, the antihypertensive TFC therapy was more effective than FCT in LVMI reduction and LVH regression, possibly related to drugs' intrinsic properties and to BPV modulation.

Topics: Amlodipine; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Combinations; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Indapamide; Male; Middle Aged; Outpatients; Perindopril; Systole; Time Factors

Poor blood pressure (BP) control contributes to complications in sub-Saharan African (SSA) type 2 diabetic individuals. Experts have advocated the use of combination therapies for effective BP control in these patients. The suggested combinations should include a RAAS antagonist and either a CCB or a thiazide diuretic; however, their efficacy is yet to be established in SSA. We investigated the short-term effects of two combination therapies on BP control in SSA type 2 diabetic individuals. This was a double-blinded randomized controlled trial conducted at the Yaoundé Central Hospital (Cameroon) from October 2016 to May 2017. We included type 2 diabetic patients, newly diagnosed for hypertension. After baseline assessment and 24-hour ABPM, participants were allocated to receive either a fixed combination of perindopril + amlodipine or perindopril + indapamide for 42 days. Data analyses followed the intention-to-treat principle. We included fifteen participants (8 being females) in each group. Both combinations provided good circadian BP control after 6 weeks with similar efficacy. Twenty-four-hour SBP dropped from 144 to 145 mm Hg vs 128 to 126 mm Hg with perindopril-amlodipine and perindopril-indapamide, respectively (P = 0.003 for both groups). Twenty-four-hour DBP dropped from 85 to 78 mm Hg (P = 0.013) vs 89 to 79 mm Hg (P = 0.006) in the same respective groups. No significant adverse effect was reported. A fixed initial combination of perindopril-amlodipine or perindopril-indapamide achieved similar effective BP control after 6 weeks in SSA type 2 diabetic individuals with newly diagnosed hypertension. Therefore, these combinations can be used interchangeably in this indication.

Topics: Africa South of the Sahara; Amlodipine; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Comorbidity; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Combinations; Drug Monitoring; Female; Humans; Hypertension; Indapamide; Male; Middle Aged; Perindopril; Treatment Outcome

Hypertension has a major associated risk for organ damage and mortality, which is further heightened in patients with prior cardiovascular events, comorbid diabetes mellitus, microalbuminuria and renal impairment. Convers Plus tablet including perindopril erbumine (PE), which is an angiotensin converting enzyme (ACE) inhibitor, and indapamide, which is diuretic, was designed as a combined tablet to succes in the treatment of hypertension. Physico-pharmaceutical properties and characterization studies were evaluated in vitro conditions. Later on in vivo study was planned as a cross-designed, randomized, open-labeled, single-dose, single-center study via peroral route in 24 healthy male subjects. In this study, bioequivalence with primary pharmacokinetical target parameters reference (Bipreterax 4/1.25 mg Tablet-S.A.Servier Benelux N.V.) and test (Convers Plus 4/1.25 mg Tablet-ARGESAN Pharmaceutical Company) tablets have been found bioequivalent. The results of pharmacokinetic parameters for perindopril, perindoprilat and indapamide were found as Cmax = 23.179 µg/mL, tmax = 0.729 h, t1/2 = 1.429 h; AUC0-t = 26.998 µgs/mL, AUC0-inf = 27.117 µgs/mL; Cmax = 1.834 µg/mL, tmax = 8.792 h, t1/2 = 40.699 h; AUC0-t = 54.828 µgs/mL, AUC0-inf = 77.113 µgs/mL; Cmax = 18.994 µg/mL, tmax = 3.417 h, t1/2 = 16.626 h and AUC0-t = 385.829 µgs/mL, AUC0-inf = 410.728 µgs/mL respectively. In conclusion, physico-pharmaceutical properties and results of clinical trials show that Convers Plus tablets have been found as bioequivalent for perindopril, perindoprilat and indapamide in terms of AUC and Cmax, in 90% confidence limits.

Topics: Administration, Oral; Adult; Angiotensin-Converting Enzyme Inhibitors; Area Under Curve; Chemistry, Pharmaceutical; Cross-Over Studies; Drug Combinations; Humans; Hypertension; Indapamide; Male; Middle Aged; Perindopril; Tablets; Therapeutic Equivalency; Young Adult

The objective of the present analysis was to determine the effects of a fixed combination of perindopril and indapamide in combination with calcium channel blockers (CCBs) in patients with type 2 diabetes mellitus. The Action in Diabetes and Vascular Disease: Preterax and Diamicron Controlled Evaluation (ADVANCE) trial was a factorial randomized controlled trial. A total of 11 140 patients with type 2 diabetes mellitus were randomly assigned to fixed combination of perindopril-indapamide (4/1.25 mg) or placebo. Effects of randomized treatment on mortality and major cardiovascular outcomes were examined in subgroups defined by baseline use of CCBs. Patients on CCB at baseline (n=3427) constituted a higher risk group compared with those not on CCB (n=7713), with more extensive use of antihypertensive and other protective therapies. Active treatment reduced the relative risk of death by 28% (95% confidence interval, 10%-43%) among patients with CCB at baseline compared with 5% (-12% to 20%) among those without CCB (P homogeneity=0.02) and 14% (2%-25%) for the whole population. Similarly, the relative risk reduction for major cardiovascular events was 12% (-8% to 28%) versus 6% (-10% to 19%) for those with and without CCB at baseline although the difference was not statistically significant (P homogeneity=0.38). There was no detectable increase in adverse effects in those receiving CCB. The combination of perindopril and indapamide with CCBs seems to provide further protection against mortality in patients with type 2 diabetes mellitus.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Dihydropyridines; Drug Combinations; Drug Therapy, Combination; Female; Gliclazide; Humans; Hypertension; Hypoglycemic Agents; Indapamide; Male; Middle Aged; Perindopril; Proportional Hazards Models

Moderate alcohol consumption has been associated with a reduced risk of mortality and coronary artery disease. The relationship between cardiovascular health and alcohol use in type 2 diabetes is less clear. The current study assesses the effects of alcohol use among participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial.. The effects of alcohol use were explored using Cox regression models, adjusted for potential confounders. The study end points were cardiovascular events (cardiovascular death, myocardial infarction, and stroke), microvascular complications (new or worsening nephropathy or retinopathy), and all-cause mortality.. During a median of 5 years of follow-up, 1,031 (9%) patients died, 1,147 (10%) experienced a cardiovascular event, and 1,136 (10%) experienced a microvascular complication. Compared with patients who reported no alcohol consumption, those who reported moderate consumption had fewer cardiovascular events (adjusted hazard ratio [aHR] 0.83; 95% CI 0.72-0.95; P = 0.008), less microvascular complications (aHR 0.85; 95% CI 0.73-0.99; P = 0.03), and lower all-cause mortality (aHR 0.87; 96% CI 0.75-1.00; P = 0.05). The benefits were particularly evident in participants who drank predominantly wine (cardiovascular events aHR 0.78, 95% CI 0.63-0.95, P = 0.01; all-cause mortality aHR 0.77, 95% CI 0.62-0.95, P = 0.02). Compared with patients who reported no alcohol consumption, those who reported heavy consumption had dose-dependent higher risks of cardiovascular events and all-cause mortality.. In patients with type 2 diabetes, moderate alcohol use, particularly wine consumption, is associated with reduced risks of cardiovascular events and all-cause mortality.

Topics: Aged; Alcohol Drinking; Antihypertensive Agents; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Drug Combinations; Female; Gliclazide; Humans; Hypertension; Hypoglycemic Agents; Indapamide; Male; Myocardial Infarction; Perindopril; Retrospective Studies; Risk Reduction Behavior; Stroke

The results of the Hypertension in the Very Elderly Trial showed positive benefits from blood pressure-lowering treatment in those aged 80 and over.. An analysis by the pre-specified subgroups [age, sex, history of cardiovascular disease (CVD) and initial SBP] was performed. The Hypertension in the Very Elderly Trial was a randomized, double-blind, placebo-controlled trial of 3845 participants aged 80 and over with SBPs of 160-199 mmHg and diastolic pressures below 110 mmHg recruited from Europe, China, Australasia and Tunisia. Active treatment was indapamide sustained-release 1.5 mg with the addition of perindopril 2-4 mg as required to reach a target blood pressure of less than 150/80 mmHg.. For total mortality, benefits were consistent: men [hazard ratio 0.82, 95% confidence interval (CI) 0.62-1.11], women (hazard ratio 0.77, 95% CI 0.66-0.99), those aged 80-84.9 (hazard ratio 0.76, 95% CI 0.60-0.96), those aged 85 and over (hazard ratio 0.87, 95% CI 0.64-1.20), those with a history of CVD (hazard ratio 0.76, 95% CI 0.48-1.20) and those without (hazard ratio 0.81, 95% CI 0.65-0.99), and similarly across a range of baseline SBPs. The point estimates for cardiovascular mortality, strokes, heart failure and cardiovascular events were all in favour of benefit. In the per-protocol analysis, strokes were reduced by 34% (P = 0.026), total mortality by 28% (P = 0.001), cardiovascular event by 37% (P < 0.001) and heart failure by 72% (P < 0.001).. In hypertensive patients aged 80 or more, treatment based on indapamide (sustained-release) 1.5 mg showed consistent benefits across pre-specified subgroups including those without established CVD (the majority), supporting the need for treatment even at this advanced age. There were too few aged 90 or over to determine benefit from treatment at extreme age.

Topics: Age Factors; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Delayed-Action Preparations; Double-Blind Method; Drug Combinations; Female; Humans; Hypertension; Indapamide; Male; Perindopril; Risk Assessment; Stroke

In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) factorial trial, the combination of perindopril and indapamide reduced mortality among patients with type 2 diabetes, but intensive glucose control, targeting a glycated hemoglobin level of less than 6.5%, did not. We now report results of the 6-year post-trial follow-up.. We invited surviving participants, who had previously been assigned to perindopril-indapamide or placebo and to intensive or standard glucose control (with the glucose-control comparison extending for an additional 6 months), to participate in a post-trial follow-up evaluation. The primary end points were death from any cause and major macrovascular events.. The baseline characteristics were similar among the 11,140 patients who originally underwent randomization and the 8494 patients who participated in the post-trial follow-up for a median of 5.9 years (blood-pressure-lowering comparison) or 5.4 years (glucose-control comparison). Between-group differences in blood pressure and glycated hemoglobin levels during the trial were no longer evident by the first post-trial visit. The reductions in the risk of death from any cause and of death from cardiovascular causes that had been observed in the group receiving active blood-pressure-lowering treatment during the trial were attenuated but significant at the end of the post-trial follow-up; the hazard ratios were 0.91 (95% confidence interval [CI], 0.84 to 0.99; P=0.03) and 0.88 (95% CI, 0.77 to 0.99; P=0.04), respectively. No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control group and the standard-glucose-control group; the hazard ratios were 1.00 (95% CI, 0.92 to 1.08) and 1.00 (95% CI, 0.92 to 1.08), respectively.. The benefits with respect to mortality that had been observed among patients originally assigned to blood-pressure-lowering therapy were attenuated but still evident at the end of follow-up. There was no evidence that intensive glucose control during the trial led to long-term benefits with respect to mortality or macrovascular events. (Funded by the National Health and Medical Research Council of Australia and others; ADVANCE-ON ClinicalTrials.gov number, NCT00949286.).

Topics: Antihypertensive Agents; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Follow-Up Studies; Gliclazide; Glycated Hemoglobin; Humans; Hypertension; Hypoglycemic Agents; Indapamide; Male; Middle Aged; Perindopril; Risk Factors

To asses differences in treatment effects of a fixed combination of perindopril-indapamide on major clinical outcomes in patients with type 2 diabetes across subgroups of cardiovascular risk.. 11,140 participants with type 2 diabetes, from the ADVANCE trial, were randomized to perindopril-indapamide or matching placebo. The Framingham equation was used to calculate 5-year CVD risk and to divide participants into two risk groups, moderate-high risk (<25% and no history of macrovascular disease), very high risk (>25% and/or history of macrovascular disease). Endpoints were macrovascular and microvascular events.. The mean age of participants was 66 years (42.5% female). 1000 macrovascular and 916 microvascular events were recorded over follow-up of 4.3 years. Relative treatment effects were similar across risk groups, (all P-values for heterogeneity ≥0.38). Hazard ratios for combined macro- and microvascular events were 0.89 (0.77-1.03) for the moderate-high risk and 0.92 (0.81-1.03) for the very high risk. Absolute treatment effects tended to be greater in the high risk groups although differences were not statistically significant (P>0.05).. Relative effects of blood pressure lowering with perindopril-indapamide on cardiovascular outcomes were similar across risk groups whilst absolute effects trended to be greater in the high risk group.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Combinations; Female; Humans; Hypertension; Indapamide; Male; Odds Ratio; Perindopril; Risk Factors; Treatment Outcome

fractures may have serious implications in an elderly individual, and fracture prevention may include a careful choice of medications.. the Hypertension in the Very Elderly Trial (HYVET) was a double-blind placebo-controlled trial of a thiazide-like diuretic (indapamide 1.5 mg SR) with the optional addition of the angiotensin-converting enzyme (ACE) inhibitor (perindopril 2-4 mg). Fracture was a secondary end point of the trial.. HYVET recruited participants from Eastern and Western Europe, China, Australasia, and Tunisia.. all participants were > or =80 years of age and hypertensive.. participants were randomised to receive a thiazide-like diuretic (indapamide 1.5 mg SR) +/- ACE inhibitor (perindopril 2-4 mg) or matching placebos. Incident fractures were validated and analysed based on time to first fracture.. there were 3,845 participants in HYVET and a total 102 reported fractures (42 in the active and 60 in the placebo group). When taking only validated first fractures, 90 were included in the analyses (38 in the active and 52 in the placebo group). Cox proportional hazard regression, adjusted for key baseline risk factors, resulted in a point estimate of 0.58 (95% CI 0.33-1.00, P = 0.0498).. despite the lowering of blood pressure, treatment with a thiazide-like diuretic and an ACE inhibitor does not increase and may decrease fracture rate.

Topics: Aged, 80 and over; Aging; Antihypertensive Agents; Blood Pressure; Drug Combinations; Female; Fractures, Bone; Humans; Hypertension; Incidence; Indapamide; Male; Perindopril; Placebos; Risk Factors

To assess the magnitude and independence of the effects of routine blood pressure lowering and intensive glucose control on clinical outcomes in patients with long-standing type 2 diabetes.. This was a multicenter, factorial randomized trial of perindopril-indapamide versus placebo (double-blind comparison) and intensive glucose control with a gliclazide MR-based regimen (target A1C 0.1): the separate effects of the two interventions for the renal outcomes and death appeared to be additive on the log scale. Compared with neither intervention, combination treatment reduced the risk of new or worsening nephropathy by 33% (95% CI 12-50%, P = 0.005), new onset of macroalbuminuria by 54% (35-68%, P < 0.0001), and new onset of microalbuminuria by 26% (17-34%). Combination treatment was associated with an 18% reduction in the risk of all-cause death (1-32%, P = 0.04).. The effects of routine blood pressure lowering and intensive glucose control were independent of one another. When combined, they produced additional reductions in clinically relevant outcomes.

Topics: Aged; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Combinations; Drug Therapy, Combination; Female; Gliclazide; Humans; Hypertension; Hypoglycemic Agents; Indapamide; Male; Microcirculation; Middle Aged; Perindopril; Placebos

Antihypertensive agents differentially influence the plasma adiponectin concentration and the effects of fixed-dose combination regimens remain unclear. The influence of a combination of an angiotensin-converting enzyme inhibitor (ACEI) and a thiazide-type diuretic or an ACEI alone on plasma adiponectin concentrations in patients with essential hypertension was evaluated in the present study.. After a 2-week placebo run-in phase, 30 patients with essential hypertension were randomized to receive preterax (2 mg perindopril/0.625 mg indapamide) or cilazapril (2.5 mg) once daily for 12 weeks. Plasma adiponectin and insulin concentrations were measured before and after treatment. Insulin resistance was measured by homeostasis assessment index (HOMA-IR). Treatment with preterax (P=0.003) and cilazapril (P=0.031) significantly reduced systolic blood pressure (BP), but only preterax reduced diastolic BP (P=0.024). Cilazapril treatment significantly increased the plasma adiponectin concentration (P=0.025) and reduced plasma triglycerides (P=0.041), whereas preterax treatment increased the plasma insulin concentration (P=0.041) and tended to increase HOMA-IR.. The combination of an ACEI and indapamide improved BP control, but attenuated the beneficial effects of ACE inhibition on plasma adiponectin in patients with essential hypertension. Such a combination may be best reserved for improved BP control rather than for metabolic protection in clinical hypertension.

Topics: Adiponectin; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biomarkers; Blood Glucose; Blood Pressure; Cilazapril; Diuretics; Double-Blind Method; Drug Combinations; Female; Humans; Hypertension; Indapamide; Insulin; Lipids; Male; Middle Aged; Perindopril; Pilot Projects; Time Factors; Treatment Outcome

Brachial blood pressure (BP) is a predictor of cardiovascular events. Evidence suggests that central BP (CBP) provides additional information for cardiovascular risk assessment. Methods to assess 24-h CBP are now available. Our objective was to assess the feasibility of 24-h CBP monitoring in clinical trials and its ability for drug evaluation.. Data are issued from an international phase 3 randomized clinical trial comparing the efficacy of perindopril/indapamide/amlodipine vs. perindopril/indapamide (Per/Ind), in uncontrolled hypertensive patients treated with Per/Ind. 24-h ambulatory BP monitoring (ABPM) was performed at baseline and after 1-month treatment using the Mobil-O-Graph device which provide brachial BP and CBP and arterial parameters.. From the 345 patients included in the ABPM substudy, 276 had two valid ABPM (M0 and M1) for brachial BP assessment (80%). After applying device/software built-in and expert quality control criteria on these recordings, 210 (76%) had valid data at M0 and M1 for the assessment of CBP. After 1 month, superior ambulatory central SBP reductions were observed in the perindopril/indapamide/amlodipine (n = 101) vs. Per/Ind group (n = 109) for 24-h/daytime/night-time periods (-4.5 mmHg, P = 0.002/-5.0, P < 0001/-4.1 mmHg, P = 0.016, respectively). Similar trends were observed for pulse wave velocity and other central parameters.. Recording 24-h central ABPM and its derived arterial parameters needs a strict expert quality control and must consider a loss of up to 39% of the population included in the ABPM substudy. This method can be used to assess drug effect.

Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Combinations; Feasibility Studies; Humans; Hypertension; Indapamide; Perindopril; Randomized Controlled Trials as Topic

In everyday medical practice, physicians often need to manage patients whose blood pressure is not well controlled. Those with a history of cerebrovascular disease are a high-risk group in need of rapid blood pressure control.. The PICASSO study was a real-life, observational trial involving 9257 inadequately treated hypertensive patients who were switched from previous therapy to the fixed-dose combination of perindopril 10 mg/indapamide 2.5 mg (PI) for 3 months. A subanalysis of data of 1117 hypertensive patients who met the clinical criteria of previous stroke or transient ischemic attack was performed. Twenty-four hour ambulatory blood pressure measurements (ABPMs) were also done in a small group of patients (n:38).. At baseline, mean systolic/diastolic blood pressure (SBP/DBP) was 161.5 ± 15.2/93.1 ± 9.9 mmHg. After 1 month with the fixed dose of PI, average office SBP/DBP decreased to 140.0 ± 11.9/83.5 ± 7.7 mmHg. After 3 months, SBP/DBP had dropped to 132.9 ± 9.8/80.0 ± 6.2 mmHg, by 28.6 ± 15.5/13.1 ± 10.0 mmHg (p < 0.001). Blood pressure control rate (< 140/90 mmHg) was 67.3% after 3 months. When data were stratified by baseline blood pressure, decreases in SBP/DBP were statistically significant in patients with all grades (1-3) of hypertension. In patients previously treated with an angiotensin-converting enzyme inhibitor ± hydrochlorothiazide (n = 677), blood pressure decreased by 29.8 ± 15.5/13.3 ± 10.2 mmHg (p < 0.001). Decreases in 24-h ABPM values were also significant (n = 38). Treatment was well tolerated; only a few adverse events were recorded.. This study suggests that fixed combination perindopril 10 mg/indapamide 2.5 mg is an effective and well-tolerated treatment for patients with a history of stroke or transient ischemic attack.. EGIS Pharmaceuticals Plc.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Combinations; Female; Humans; Hungary; Hypertension; Indapamide; Ischemic Attack, Transient; Male; Middle Aged; Perindopril; Stroke; Treatment Outcome

to assess antihypertensive efficacy of the fixed-dose amlodipine/indapamide/perindopril arginine combination in hypertensive patients in real clinical setting.. We included in the 3‑month clinical program 1 599 patients with arterial hypertension (AH) (38.8 % men, mean age 61.6±10 years). Primary outcomes were change of office and ambulatory (home blood pressure monitoring) systolic and diastolic blood pressure (SBP and DBP) from baseline to 3 months and rate of achievement of target BP.

Topics: Academic Medical Centers; Aged; Amlodipine; Antihypertensive Agents; Arginine; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Combinations; Female; Humans; Hypertension; Indapamide; Male; Middle Aged; Patient Compliance; Perindopril; Russia

to assess adherence of patients to antihypertensive therapy with fixed perindopril and indapamide combination (FPIC) as well as to elucidate causes of changes of therapy after 6 months.. In 6 months after termination of the FORSAGE observational program we interviewed over telephone 148 of 1299 patients who achieved target blood pressure (BP) values.. Adherence to treatment was high - 67.5% of patients continued to take the drug. In 87.9% of patients BP was kept on target level (<140 and 90 mm Hg), in 12.1% BP was above this level. Most patients were satisfied by results of treatment. Infrequent hypertensive crises persisted in 6.1% of patients; 3% of patients sought emergency service. Among 48 patients who stopped taking FPIC 22 (45.8%) made this decision themselves, 11 - on physicians advice. Main causes of cancellation of treatment were high cost of the drug, its absence in the list of concessional mediciations, physicians statement "course treatment completed, condition improved". Among those who stopped treatment 10 patients could not report values of their BP; in 28 (58.3%) BP was at and in 10 (20.8%) above target level; crises were registered in 8.3% of patients, 4.2% of patients called ambulances, 1 patient suffered stroke. Of 48 patients who stopped treatment with FLIC 19 consented to self report assessment health status; 84% of reported scores were above 5, but no score was equal to 9 or 10.

Topics: Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Combinations; Drug Therapy, Combination; Humans; Hypertension; Indapamide; Medication Adherence; Perindopril; Stroke

Blood pressure (BP) control in hypertensive patients remains poor worldwide, particularly in high-risk patients with hypertension and diabetes. Guidelines recommend that such patients receive prompt pharmacological therapy at maximal doses to rapidly control BP. We aimed to evaluate efficacy and safety of single-pill combination (SPC) perindopril/indapamide (PER/IND) at full dose (10/2.5 mg) in hypertensive patients, including diabetics, with BP uncontrolled by previous medication.. Twelve-week prospective, observational study in patients with uncontrolled hypertension (≥160-200 mmHg systolic BP [SBP] and <110 mmHg diastolic BP [DBP]) on a previous SPC or free-dose combination of renin-angiotensin system blocker plus thiazide diuretic, substituted with PER/IND 10/2.5 mg. Office BP, quality of life, and blood parameters were evaluated in the whole cohort and patients with type 2 diabetes mellitus.. 2120 ambulatory hypertensive patients were enrolled, including 307 with type 2 diabetes. Two weeks after substitution, SBP significantly decreased from 171.0 ± 13.3 to 148.6 ± 13.4 mmHg, and DBP from 98.6 ± 8.3 to 88.8 ± 7.9 mmHg (both p < 0.00001). A similar rapid decrease was noted in the diabetes subgroup. After 12 weeks, BP had reduced by 42/19 mmHg in the whole cohort (diabetes subgroup: 41/18 mmHg). Most (84%; diabetes subgroup: 77%) patients reached BP target (<140/90 mmHg). Laboratory tests and quality of life improved in the whole cohort and the diabetic subgroup.. Switching to PER/IND at full dose (10/2.5 mg) was well tolerated, leading to fast BP reduction and control in the majority of patients with uncontrolled hypertension, including difficult-to-treat patients with diabetes.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Diabetes Mellitus, Type 2; Diuretics; Drug Combinations; Drug Resistance; Female; Humans; Hypertension; Indapamide; Male; Middle Aged; Perindopril; Prospective Studies; Treatment Outcome

To measure the placebo-controlled effects of combination therapy on hypotension, treatment discontinuation, and major renal outcomes, according to baseline blood pressure.. We conducted an analysis of the action in diabetes and vascular disease: preterax and diamicron-MR controlled evaluation ADVANCE and perindopril protection against recurrent stroke study PROGRESS trials, including 14 684 participants allocated combination therapy or placebo. The mean age was 65 years, 61% were men, and 64% were receiving background blood pressure lowering (BPL) therapy. Participants were stratified into five subgroups by baseline SBP less than 120, 120-129, 130-139, 140-159, and at least 160 mmHg. Discontinuation of study treatment during the active run-in phase and postrandomization follow-up was assessed for hypotension/dizziness and other causes. Major renal outcomes (sustained doubling in creatinine or renal death) were also assessed.. Discontinuation during the 4-6-week active run-in phase due to hypotension/dizziness ranged from 3.6% in those with SBP less than 120 mmHg to 1.3% in those with SBP at least 160 mmHg. Median follow-up in the randomized phase was 5.6 years, and discontinuation for hypotension was higher with combination therapy compared with placebo in the less than 120 mmHg group (4.7 vs. 1.2%). However, for each subgroup with baseline SBP 120-129, 130-139, and 140-159 mmHg, the absolute excess of discontinuation due to hypotension with combination therapy was 0.7%. Total discontinuations were only increased in the less than 120 mmHg group (18.4 vs. 12.5%) and the 120-129-mmHg subgroup (17.6 vs. 14.2%). There were no clear differences across the SBP subgroups for the combined renal outcome (overall, 0.8 vs. 0.6%).. Compared with those with baseline SBP 140-159 mmHg, side effects of dual combination BPL are essentially the same for people with SBP 130-139 mmHg and only modestly increased among patients with SBP 120-129 mmHg. During long-term therapy, side effects sufficient to stop treatment that are treatment related (i.e. occur in excess of rates seen with placebo) occur at less than 0.5%/year in patients with baseline SBP 120-139 mmHg. These results have important implications in assessing the likely balance of benefits and side effects of BPL with combination therapy among those with SBP 120-139 mmHg.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Diabetes Mellitus, Type 2; Drug Combinations; Female; Humans; Hypertension; Hypotension; Indapamide; Male; Medication Adherence; Middle Aged; Multicenter Studies as Topic; Perindopril; Placebos; Proportional Hazards Models; Randomized Controlled Trials as Topic; Stroke

to assess the potential of fixed perindopril/indapamide combination (FPIC) to improve angioprotection in patients with arterial hypertension (AP) with various efficacy of preceding therapy with combination of losartan and hydrochlorothiazide (HCTZ).. We included in this open study 50 patients with AP divided into two equal-sized groups in dependence on the achievement of target blood pressure (BP) less than 140/90 mm Hg on preceding therapy with losartan (100 mg) and HCTZ (12.5 mg). All patients underwent ambulatory BP monitoring (ABPM), applanation tonometry (assessment of augmentation index and central blood pressure), measurement of pulse wave velocity (PWV), laboratory tests (lipid profile, fasting glucose, HOMA index, homocysteine, leptin, adiponectin, high sensitivity C reactive protein [hsCRP]). Study duration was 12 weeks.. Treatment with FPIC in patients not at target BP provided 14.5 and 6.6% reduction of systolic and diastolic BP (SBP and DBP), respectively (p<0.01), while in patients with target BP it was associated with additional reductions of SBP and DBP by 3.9 and 5.4%, respectively (p<0.01). According to ABPM data average day- and nighttime SBP decreased by 16.9 and 15.0%, average day- and nighttime DBP - by 10.6 and 13.6% (p<0.01) in the group of patients not at target BP. Reductions of PWV (by 15.2 and 2.2%), augmentation index (by 10.7 and 9.4%), central SBP (by 10.9 and 2.1%), central pulse BP vascular age (by 8.7 and 6.0%) were observed in groups of patients without and with target BP on preceding therapy, respectively (p<0.01). Leptin level decreased by 10.0 and 14.4%, hsCRP - by 17.7 and 11.0%; while level of adiponectin increased by 6.7 and 9.9% (p<0.01).. Our results demonstrated advantages of FPIC over losartan+HCTZ combination relative to BP control, improvement of arterial elasticity, alleviation of insulin resistance and inflammation.

Topics: Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Combinations; Humans; Hypertension; Indapamide; Metabolic Diseases; Perindopril; Pulse Wave Analysis

im of the study - to evaluate the possibility of increasing the effectiveness of antihypertensive therapy by simplifying regimens, improving knowledge and practical skills of the doctors on the use of modern tactical approaches to treatment as well as patients education methods of measuring blood pressure (BP), the principles of a healthy lifestyle and explain the need to follow the prescribing physician.. Post-marketing observational discovery program FORSAZH held in 29 cities of the Russian Federation. Participation in the program received 442 physician (internists and general practitioners), which included 1969 patients with prior failure of combination antihypertensive therapy. Patients in 86% of cases took the free combination, 14% - fixed combinations of drugs. The change of the treatment on reception of a preparation containing a fixed combination of perindopril/indapamide (10 mg/2.5 mg) after 3 months led to decrease in systolic blood pressure by an average of 39.5 mm Hg, diastolic - 18.7 per mm Hg. The frequency of achieving the target BP <140 mm Hg and 90 it was 76%. Marked reduction in BP and frequency to achieve the target BP is not dependent on additional training of physicians and patients, the use of prior therapy in free or fixed combination, but depended on the initial degree of increase in BP and duration of therapy. Predictors of failure to achieve target BP were age, male gender, low initial adherence, good health, a higher baseline BP, elevated cholesterol levels, body weight, heart rate and decreased glomerular filtration rate. Adherence to therapy patients (on a scale of Morisky-Green) and health assessment on a visual analog scale significantly increased. This tactic has been a change of therapy is not only effective but also safe. Adverse events were reported in 28 patients (1.4% of the total number of observed cases) and only 1 case required dose reduction due to development of clinically manifested hypotension.. In enhancing the effectiveness of the treatment of patients with hypertension was decisive simplification of drug therapy through the use of a fixed combination of perindopril A/indapamide.

Topics: Antihypertensive Agents; Blood Pressure; Drug Combinations; Drug Therapy, Combination; Female; Heart Rate; Humans; Hypertension; Indapamide; Male; Middle Aged; Perindopril; Russia

Topics: Calcium Channel Blockers; Diabetes Mellitus, Type 2; Dihydropyridines; Drug Combinations; Female; Gliclazide; Humans; Hypertension; Indapamide; Male; Perindopril

Hypertension and type 2 diabetes mellitus (T2DM) synergistically deteriorate the vascular environment, making blood pressure reduction challenging, and substantially increasing cardiovascular risk.. In the real-life, open-label, observational, PICASSO study, 9,257 hypertensive patients unsuccessfully treated with antihypertensives were switched to fixed-dose combination of perindopril 10 mg/indapamide 2.5 mg. In this subgroup analysis, we analyzed changes in blood pressure and laboratory parameters of 2,762 hypertensive patients with T2DM or pre-diabetes.. After 3 months of treatment, significant decreases in office blood pressure were noted in the whole cohort (-27.0±14.8/-12.7±9.8 mmHg; p<0.001). Significant decreases were also recorded in patients with grade 1 hypertension (19.2±10.0/-9.4±7.9 mmHg), grade 2 (29.2±10.9/-13.3±8.7 mmHg) and grade 3 (-45.1±15.4/-21.5±11.2 mmHg). Significant decreases in ambulatory blood pressure were also noted (n=93). In patients previously treated with angiotensin-converting enzyme inhibitor±hydrochlorothiazide or angiotensin receptor blocker±hydrochlorothiazide, mean 24-h blood pressure decreased by 23.4±13.9/11.5±9.7 and 22.3±8.7/10.4±13.2 mmHg, respectively (p<0.001). Treatment was well tolerated and the switch to treatment with perindopril/indapamide was associated with improvements in laboratory parameters.. Data from this diabetes subgroup analysis suggest that fixed combination of perindopril 10 mg/indapamide 2.5 mg should be routinely considered for the treatment of hypertension in diabetic patients who are unsuccessfully managed with other antihypertensive medications.

Topics: Aged; Antihypertensive Agents; Blood Pressure Monitoring, Ambulatory; Diabetes Mellitus, Type 2; Drug Combinations; Female; Humans; Hypertension; Indapamide; Male; Middle Aged; Perindopril; Prediabetic State; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Our objective was to evaluate a triple-drug antihypertensive strategy for blood pressure control in patients with difficult-to-treat hypertension.. The Perindopril-Indapamide plus AmlodipiNe in high rISk hyperTensive patients (PIANIST) trial was an observational, 4-month, open-label study.. A total of 4,731 patients at high or very high cardiovascular risk with hypertension that was not properly controlled [ , and for [corrected] whom study treatment (fixed-dose perindopril 10 mg/indapamide 2.5 mg + amlodipine 5 or 10 mg) was consistent with their existing therapeutic plan, were included.. One-sample t tests and Chi-squared tests were performed to evaluate changes in blood pressure.. Mean baseline office blood pressure (OBP) was 160.5 ± 13.3/93.8 ± 8.7 mmHg. After 4 months of therapy, OBP decreased by 28.3 ± 13.5/13.8 ± 9.4 to 132.2 ± 8.6/80.0 ± 6.6 mmHg (p < 0.0001). Blood pressure targets were reached by 72.0% of patients and by 81 and 91% of patients previously treated with an angiotensin-converting enzyme inhibitor/hydrochlorothiazide or an angiotensin receptor blocker/hydrochlorothiazide, respectively. Changes in OBP were 18.7 ± 8.3/9.7 ± 7.2 mmHg for grade 1 (n = 1,679), 30.4 ± 10.1/14.7 ± 8.6 mmHg for grade 2 (n = 2,397), and 45.4 ± 15.1/20.7 ± 12.1 mmHg for grade 3 patients (n = 655; all p < 0.0001). In patients who underwent ambulatory blood pressure monitoring (n = 104), 24-h mean blood pressure decreased from 147.4 ± 13.8/82.1 ± 11.9 to 122.6 ± 9.1/72.8 ± 7.4 mmHg (p < 0.0001). Ankle edema was infrequent (0.2% of patients).. Triple combination perindopril/indapamide/amlodipine was effectively and safely administered to a large population of high- and very high-risk hypertensive patients who had not reached target OBP values with previous treatment.

Topics: Adult; Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Combinations; Drug Therapy, Combination; Female; Heart Rate; Humans; Hypertension; Indapamide; Male; Middle Aged; Perindopril; Prospective Studies; Risk Factors

In the Russian program FORTISSIMO administration of fixed combination of perindopril arginine/indapamide (10 mg/2.5 mg) in 2120 patients with poorly controlled arterial hypertension instead of angiotensin converting enzyme inhibitors (ACEI) or -receptor antagonists (ARB) with hydrochlorothiazide given separately or in fixed combinations resulted in significant lowering of arterial pressure (AP) and achievement of its target level in 84% of patients. Mean AP was lowered from 177/99 to 130/80 mm Hg in 3 months while substantial reduction down to 149/89 mm Hg occurred just after 2 weeks of treatment. Improvement of compliance to therapy was also noted. Fixed perindopril/indapamide combination was well tolerated and turned out to be effective for AP control irrespective of previously conducted therapy (ACEI or ARB with diuretic).

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Disease Management; Dose-Response Relationship, Drug; Drug Combinations; Drug Monitoring; Drug Resistance; Female; Humans; Hypertension; Indapamide; Male; Medication Adherence; Middle Aged; Perindopril; Program Development; Prospective Studies; Risk Factors; Russia; Treatment Outcome

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Drug Combinations; Drug Monitoring; Drug Resistance; Female; Humans; Hypertension; Indapamide; Male; Medication Adherence; Middle Aged; Perindopril; Program Development; Prospective Studies; Risk Factors; Russia; Treatment Outcome

The aim of the study was to investigate the dynamics of arterial stiffness and endothelial function parameters under the influence of perindopril arginine and indapamide fixed combination in arterial hypertension (AH) patients. 30 persons with 1-3 degree AH were included into the study. The treatment duration was 24 weeks. Central aortic blood pressure (BP), augmentation pressure and index (AIx), carotid-femoral and carotid-radial pulse wave velocity (PWV), brachial artery endothelium-dependent vasodilatation (EDVD), office and ambulatory BP as well as orthostatic BP falls were evaluated under the influence of selected therapy. 27 patients completed the study protocol. Results showed that aortic systolic BP was significantly reduced by 10.7 mmHg, augmentation pressure - by 3.6 mmHg and AIx - by 6.5%. Carotid-radial PWV decreased by 0.8 m/s. Carotid-femoral PWV did not change. We also revealed the EDVD increase by week 12. The EDVD growth was correlated with degree of aortic systolic BP reduction (r=-0.48, p=0.02). Office and ambulatory BP declined by 15.8/10.0 and 10.0/7.5 mmHg respectively. The target BP <140/90 mmHg was achieved in 20 (74.1%) persons. At the same time the orthostatic hypotension did not rise. Conclusion. We concluded that perindopril arginine/indapamide fixed combination improved vascular function in hypertensive patients by wave reflection reduction, peripheral arterial stiffness lowering and endothelial function improvement.

Topics: Administration, Oral; Antihypertensive Agents; Arteries; Biological Availability; Blood Pressure; Drug Combinations; Drug Synergism; Endothelium, Vascular; Female; Humans; Hypertension; Indapamide; Male; Middle Aged; Perindopril; Pulse Wave Analysis; Treatment Outcome; Vascular Resistance; Vasodilation

Topics: Antihypertensive Agents; Clinical Trials as Topic; Drug Combinations; Humans; Hypertension; Indapamide; Perindopril

The objective of the FALCO FORTE programme was to demonstrate the efficacy and safety of 3 months of therapy with the fixed combination perindopril/indapamide in hypertensive patients in everyday medical practice.. Patients with blood pressure >140/90 mmHg or with blood pressure >130/85 mmHg and three or more risk factors were prescribed perindopril/indapamide 2.5/0.625 mg or 5/1.25 mg. Dosage could be increased to 10/2.5 mg at any time during the study.. Of the 2327 patients included, 69% of patients had been unsuccessfully treated with other antihypertensives, 4.6% had not tolerated previous antihypertensive treatments, and 26.8% were newly diagnosed hypertensive patients. Roughly half the cohort was at high or very high cardiovascular risk. After 3 months of therapy, systolic blood pressure decreased from 156.9 ± 13.7 to 132.3 ± 10.6 mmHg (p < 0.0001) and diastolic blood pressure from 94.9 ± 8.2 to 81.3 ± 6.3 mmHg (p < 0.0001). Target blood pressure was reached by 87.1% of patients. Similar changes from baseline were observed in patients with diabetes mellitus, metabolic syndrome or left ventricular hypertrophy (p < 0.0001). When blood pressure decreases were analysed by dose, changes from baseline increased with increasing doses. Perindopril/indapamide was well tolerated with no significant changes in laboratory parameters being observed. Quality of life improved significantly.. Therapy with fixed combination perindopril/indapamide was effective and well tolerated in a wide range of patients.

Topics: Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Chi-Square Distribution; Diuretics; Drug Combinations; Female; Humans; Hypertension; Indapamide; Male; Middle Aged; Perindopril; Prospective Studies; Quality of Life; Risk Assessment; Risk Factors; Slovakia; Time Factors; Treatment Outcome

Topics: Adiponectin; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biomarkers; Blood Glucose; Blood Pressure; Cilazapril; Diuretics; Drug Combinations; Humans; Hypertension; Indapamide; Insulin; Lipids; Perindopril; Time Factors; Treatment Outcome

Preterax is the first fixed very- low - dose combination of an angiotensin--converting enzyme inhibitor and a diuretic for first line treatment of hypertension. Its antihypertensive efficacy is remarkable due to the presence of 2 drugs with additional effects. The tolerance is also excellent, with adverse effects similar to placebo. The 24 h blood pressure control is maintained. If necessary, the dose can be doubled (BiPreterax). The medical practitioner must keep in mind that it is an association of perindopril 2 mg and indapamide 0.625 mg with their own contra-indications. These low dose associations are now recommended as one of the 2 options to initiate an antihypertensive drug treatment, with the hope of an improvement in the percentage of well controlled blood pressure in the hypertensive population. Let us remember that the blood pressure target to be reached is at least < 140/90 mmHg. Up till now, no antihypertensive class has demonstrated a superiority over the others. Only the blood pressure fall magnitude is important to prevent cardiovascular complications.

Topics: Drug Combinations; Humans; Hypertension; Indapamide; Perindopril; Remission Induction; Time Factors

The goal of this study was to assess the effect of acute or chronic treatment with S5590, a combination of the angiotensin-converting enzyme inhibitor perindopril (0.76 mg/kg/day) and the diuretic indapamide (0.24 mg/kg/day) on renal function in spontaneously hypertensive rats with moderate renal injury. Renal function was evaluated in conscious rats by clearance methods using labelled inulin and PAH, after catheterisation of the carotid artery, jugular vein and bladder. Both acute and chronic treatment normalised renal vascular resistance, although the effect on blood pressure was more marked after chronic than after acute treatment. Although acute treatment with S5590 increased glomerular filtration rate and renal blood flow, chronic treatment did not affect these parameters. Diuresis and natriuresis were only slightly modified and the results suggest a marked renal vasodilatation. In conclusion, the maintenance of renal function after chronic treatment, in a setting of normalisation of arterial pressure, suggest that such a combined treatment may exert marked renal functional protective effects in hypertension.

Topics: Animals; Antihypertensive Agents; Diuresis; Diuretics; Dose-Response Relationship, Drug; Drug Combinations; Hypertension; Indapamide; Kidney; Natriuresis; Perindopril; Rats; Rats, Inbred SHR; Rats, Inbred WKY