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PubMed2003

The Perindopril Protection Against Recurrent Stroke Study (PROGRESS): clinical implications for older patients with cerebrovascular disease.

Blood pressure levels are strongly predictive of the risks of first-ever and recurrent stroke. The benefits of blood pressure-lowering therapy for the prevention of fatal and non-fatal stroke in middle-aged individuals are well established. However, until recently, there has been uncertainty about the consistency of such benefits across different patient groups and in particular, for older people and in those with a history of stroke. This paper discusses the evidence surrounding the effectiveness of blood pressure-lowering therapy, specifically in older patients with a history of stroke, with particular attention paid to the results from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). PROGRESS was a randomised, double-blind, placebo-controlled trial of 6105 individuals with a history of cerebrovascular disease recruited from 172 hospital outpatient clinics in ten countries. Participants (mean age 64 years; range 26-91 years) were randomly assigned to receive active treatment with an ACE inhibitor-based blood pressure-lowering regimen (perindopril) with or without addition of the diuretic indapamide, or matched placebo. At the end of follow up (mean of 4 years), active treatment reduced the incidence of total stroke by 28% (95% CI 17-38%) and the rate of major vascular events by 26% (95% CI 16-34%). Importantly, benefits of treatment were consistent across key patient subgroups, including those with and without hypertension, patients who were Asian and non-Asian, and for both ischaemic and haemorrhagic strokes subtypes. Current evidence is now strong for clinicians to consider blood pressure-lowering therapy as pivotal in the prevention of stroke, especially in patients with a known history of cerebrovascular disease (and vascular disease, in general), irrespective of blood pressure levels, as soon as patients are clinically stable after an acute stroke or other vascular event. Additional age-specific analyses of the PROGRESS data, together with those from other completed trials, will provide more reliable information about the size of the benefits of blood pressure-lowering therapy, specifically for different age groups, and particularly in the oldest old (those aged >80 years). In the meantime though, an ACE inhibitor plus diuretic treatment regimen that maximises the degree of blood pressure reduction has a good safety profile and is an effective treatment that should be considered in all patients with stroke, including the elderly.

Aged↗
PubMed1988

Effects of diuretic drugs on the lipid profile.

Thiazide-type diuretic drugs modify the lipoprotein profile when used in the short term treatment of hypertension. Total cholesterol increases by 6 to 7% on average because of raised concentrations of low density or very low density lipoprotein cholesterol or both. High density lipoprotein cholesterol does not change. Spironolactone has a lesser effect on lipids than do thiazides. In contrast, the methylindoline compound, indapamide, a diuretic with vasodilator activity, has produced no adverse effects on lipids or lipoproteins. Long term data on thiazide monotherapy are sparse but suggest a persistence of the lipid effect for as long as 6 years of treatment. The clinical impact of these lipid changes is unclear. Although clinical trials have proved the benefit of lowering cholesterol on the incidence of coronary heart disease, the clinical significance of these diuretic-induced increases is unknown. A clinical trial will be required to resolve the issue by comparing antihypertensive drugs with and without adverse effects on the lipid profile. Because coronary heart disease is the most common complication of mild hypertension, and as diuretic-based regimens have not succeeded in curbing it, resolution of this concern is important.

Benzothiadiazines↗
PubMedDate not supplied

Blood pressure lowering for the prevention of cognitive decline in patients with cerebrovascular disease. PROGRESS Management Committee. Perindopril Protection Against Recurrent Stroke Study.

Cerebrovascular disease and high blood pressure both appear to increase the risk of vascular dementia. PROGRESS aims to investigate whether blood pressure lowering with an angiotensin coverting enzyme inhibitor-based regimen will reduce the risk of cognitive impairment in patients with a history of stroke or transient ischaemic attack. A total of at least 6000 patients will be randomised to receive perindopril (+/- indapamide) or matching placebo(s), with treatment and follow-up scheduled to continue for at least 4 years. Substudies will investigate the effects of treatment on cognitive decline in subgroups defined by apo-E genotype and on white matter lesions assessed by magnetic resonance imaging. Final results from the study should be available in 2001.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Efficacy and safety of an oral fixed low-dose perindopril 2 MG/indapamide 0.625 MG combination: a randomized, double-blind, placebo-controlled study in elderly patients with mild to moderate hypertension.

The efficacy and safety of 12 weeks treatment with an oral fixed low-dose perindopril 2 mg + indapamide 0.625 mg (Per/Ind) combination in elderly and very elderly patients (65-85 years) with mild to moderate systolic and diastolic hypertension (SDH) or isolated systolic hypertension (ISH) were investigated vs placebo. This trial was a multinational randomized double-blind study with doubling of active drug dosage in nonresponders. Intention to treat analysis was performed in 383 patients (age 72.4 years; ISH 32%). 58.5% remained on their initial dosage. Per/Ind decreased supine diastolic and systolic blood pressure (sDBP/sSBP) by 13.2+/-8.0 mm Hg and 22.5+/-13.9 mm Hg (P <.0001) versus placebo -7.3+/-9.0 mm Hg and -12.3+/-15.2 mm Hg, respectively. In ISH (n = 123), Per/Ind decreased sSBP by 23.0+/-11.8 mm Hg (P <.0001). Overall response and normotension rates was 81.3% with Per/Ind (P <.0001). Adverse event rates (including hypokalemia) were similarly low in both groups. Analysis in the over-75 year subgroup showed similar safety and efficacy results. Fixed low-dose Per/Ind is a safe and effective treatment of hypertension including isolated systolic hypertension in the elderly.

Administration, Oral↗
PubMed2001

Effects of combination of low doses of angiotensin-converting enzyme inhibitor and diuretics on renal function in spontaneously hypertensive rats: comparison between acute and chronic treatment.

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.

Animals↗
PubMed1999

PROGRESS - Perindopril Protection Against Recurrent Stroke Study: characteristics of the study population at baseline. Progress Management Committee.

OBJECTIVE: The primary aim of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) is to determine the effects of a long-term angiotensin converting enzyme (ACE)-inhibitor-based blood-pressure-lowering regimen on the risk of stroke among patients with a history of stroke or transient ischaemic attack (TIA). Secondary aims include investigation of the effects of treatment on total cardiovascular events, dementia and disability. DESIGN AND METHODS: PROGRESS is a double-blind, placebo-controlled randomized trial. Patients were randomly assigned to treatment with the ACE inhibitor perindopril (and the diuretic indapamide for those with no definite indication or contraindication to treatment with a diuretic) versus matching placebo(s). Both hypertensive and non-hypertensive patients were eligible for inclusion. Follow-up is scheduled for completion in 2001. The study is being conducted in 172 centres in 10 countries (Australia, Belgium, China, France, Italy, Ireland, Japan, New Zealand, Sweden and the United Kingdom). RESULTS: Recruitment was completed in November 1997, with 6105 patients randomized. Mean age of participants at study entry was 64 years, 30% of whom were female, 84% had an entry diagnosis of stroke, and the remainder had an entry diagnosis of TIA alone. Mean baseline blood pressure was 147/86 mm Hg, with about half the patients reporting current drug treatment for hypertension. At randomization, 58% of patients were assigned to combination treatment with both study drugs versus placebos, and 42% were assigned to perindopril alone versus placebo. CONCLUSIONS: The successful completion of recruitment, together with current indicators of statistical power, suggest that PROGRESS should achieve its primary aim on schedule.

Aged↗
PubMed2000

PROGRESS (Perindopril Protection Against Recurrent Stroke Study): regional characteristics of the study population at baseline. PROGRESS Management Committee.

OBJECTIVE: To determine the effects of an angiotensin-converting enzyme (ACE) inhibitor-based blood pressure lowering regimen on the risk of stroke among patients with a history of cerebrovascular disease. Secondary aims include investigation of the effects of treatment on other cardiovascular events, dementia, and disability. DESIGN AND METHODS: PROGRESS (Perindopril Protection Against Recurrent Stroke Study) is a double-blind, placebo-controlled, randomized trial being conducted in 172 centres in 10 countries (Australia, Belgium, China, France, Italy, Ireland, Japan, New Zealand, Sweden, and the United Kingdom). Patients were randomly assigned to treatment with the ACE inhibitor perindopril (and the diuretic indapamide for those with no definite indication for or contraindication to treatment with a diuretic) or matching placebo(s). Both hypertensive and normotensive patients were eligible for inclusion. Follow-up is scheduled for completion in 2001. RESULTS: Of 6105 patients randomly allocated to study groups on completion of recruitment in November 1997, 1110 were recruited from Australia and New Zealand, 1520 from China, 713 from France and Belgium, 557 from Italy, 815 from Japan, 675 from Sweden, and 715 from the UK and Ireland. Regional differences in the baseline characteristics included a greater rate of diabetes, lacunar infarction, and cerebral haemorrhage in patients from China and Japan, and a more frequent history of myocardial infarction in Australia and New Zealand. Previous treatment with calcium antagonists was very frequent in Japan and China, whereas diuretic treatment was most often documented in the UK and Ireland. CONCLUSIONS: Analysis of baseline characteristics of patients recruited from seven distinct geographic regions revealed some interesting differences, but more striking was the consistency of characteristics of patients recruited from many different countries across the world.

Aged↗
PubMed2001

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.

Antihypertensive Agents↗
PubMed2002

Effects of antihypertensive therapy on hemorheological profiles in female hypertensive patients with initially low or high whole blood viscosity.

This study was designed to examine changes of hemorheological parameters in essential arterial hypertension subjects following antihypertensive drug therapy. Eighty two female subjects were enrolled, and sub-divided into two groups based upon their high shear whole blood viscosity being lower (L) or higher (H) than normal controls. Equal numbers of L and H subjects were then treated for four weeks with one of four agents: angiotensin-converting enzyme inhibitor (ACE-inhibitor, Spirapril - 6 mg/day); calcium antagonist (Isradipin - 5 mg/day); beta-1-blocker (Talinolol - 100 mg/day); diuretic (Indapamide - 1.5 mg/day). Both prior to and following drug treatment for six weeks, hemorheological measurements included plasma viscosity; high and low shear whole blood viscosity, hematocrit, fibrinogen and RBC aggregation. Treatment with each of the four drugs significantly (p<0.05) reduced blood pressure in both the L and H groups. However, the hemorheological effects of antihypertensive drug therapy differed markedly between groups: plasma and whole blood viscosity were significantly elevated in the L groups whereas these parameters were significantly decreased in the H groups. Fibrinogen levels and RBC aggregation decreased in both groups, whereas hematocrit was unaffected. These results thus suggest that the rheologic effects of antihypertensive drug therapy depend strongly on the initial, pre-treatment status of the subject, and that for some subjects, such therapy can result in adverse hemorheological alterations.

Antihypertensive Agents↗
PubMed2002

[The challenge to treat hypertensive patients with type 2 diabetes].

A MAJOR PROBLEM: High blood pressure and type 2 diabetes is a increasingly frequent condition. Microalbuminuria is an independent risk factor of cardiovascular complications. THERAPEUTIC STRATEGY: Because of the risk of cardiovascular disease, a treatment designed to lower the blood pressure should also reduce the microalbuminuria. Indapamid SR is an excellent choice.

Adult↗
PubMed2002

Effects of four antihypertensive monotherapies on cardiac mass and function in hypertensive patients with left ventricular hypertrophy: randomized prospective study.

AIM: To compare the effects of four antihypertensive drugs, which have reportedly different effectiveness in reducing myocardial mass. METHODS: A randomized, double-blind, prospective study included 80 hypertensive patients with left ventricular (LV) hypertrophy confirmed both electrocardiographically and echocardiographically. We investigated the effects of indapamide, nicardipine, propranolol, and chlorthalidone on arterial blood pressure and LV mass and function. RESULTS: Sixty-four patients (34 men and 30 women) completed the 6-month study. No significant differences in antihypertensive effects of the four medications were found. The average decrease in systolic and diastolic blood pressure was 12.8% and 10.4%, respectively. All four antihypertensive medications caused pronounced reduction in LV mass, between 7.9% in the propranolol group and 10.1% in the nicardipine group, with no significant difference between the groups. In patients receiving diuretics, predominant decrease was observed in LV mass and LV mass index. In patients treated with propranolol, the thickness of both the LV wall and interventricular septum was reduced, whereas the reduction in LV mass, LV wall and interventricular septum thickness was found in patients treated with nicardipine. There was no significant correlation between the changes in LV mass and other variables (blood pressure, and systolic and diastolic function). Systolic function did not improve with the reversion of LV hypertrophy in any group of patients, but improvement was observed in some indices of diastolic function. The early and late LV filling velocity and their ratio did not improve significantly, either. Clinically relevant side effects were not observed. CONCLUSION: All four antihypertensive monotherapies achieved a comparable control of hypertension and reduction in LV hypertrophy.

Adult↗
PubMed2003

[Structural and functional changes of the microcirculation in hypertension: influence of pharmacological therapy].

The increased peripheral resistance in hypertension results from arteriolar vasoconstriction, increased media-to-lumen (M/L) ratio of small resistance arteries, and rarefaction (reduction in density) of microvessels. Numerous neurohumoral and hormonal factors are involved in causing structural and functional changes in the microcirculation in hypertension, including the renin-angiotensin-aldosterone system, remodelling of the extracellular matrix, increased growth of the smooth muscle cells of the media, and elevated collagen and fibronectin deposition. Although a wide variety of pharmacological agents can decrease blood pressure (BP) in hypertension, they vary in their ability to reverse structural and functional changes in the microcirculation. ACE inhibitors have consistently been shown to regress microvascular changes but findings with calcium antagonists have been variable and beta-adrenoceptor blockers appear to have no effect. In studies with ACE inhibitors, improvements in the M/L ratio and endothelial function of small resistance arteries have been recorded in both animal models of hypertension and human subcutaneous arteries obtained by biopsy of gluteal tissue from patients with essential hypertension. Recent studies with the very low-dose combination of perindopril and indapamide have indicated that these agents act synergistically to restore normal microvascularisation and reverse capillary rarefaction in the coronary circulation of hypertensive rats, and normalise coronary blood flow reserve in humans with hypertension. The additional benefit accruing from regression of structural and functional abnormalities in critical vascular beds such as coronary or renal circulations of patients with chronic hypertension may well become an important factor in selection of antihypertensive therapy, as complications such as ischaemic episodes and other target organ damage may be prevented and the BP-lowering effect of treatment may be extended such that it continues even after withdrawal. However, whether improvements in microcirculatory structure and function will be associated with improved morbidity and mortality outcomes in patients with chronic hypertension has yet to be firmly established.

Adrenergic beta-Antagonists↗
PubMed2003

Making PROGRESS in stable patients post stroke or transient ischaemic attack: implications for general practice.

Stroke is a major cause of morbidity and mortality. Those who survive have a one in six chance of a further stroke in the ensuing five years. The perindopril protection against recurrent stroke study (PROGRESS) is the first specific trial to address whether blood pressure lowering in hypertensive or non-hypertensive patients with a history of stroke or transient ischaemic attack (TIA) would reduce subsequent cerebrovascular and cardiovascular events. Results show that treatment based on perindopril significantly reduces stroke (28%), cardiovascular events (26%) and heart failure (26%). Stable patients post stroke should be considered for perindopril, and indapamide if possible, along with other evidence based risk reduction treatments (e.g. aspirin, statins). Therapy can be initiated and monitored either from hospital outpatients or general practice or both in co-operation.

Aged↗
PubMed2003

[Effect of combined antihypertensive and lipid lowering therapy on the level of coronary risk and tissue insulin resistance in patients with metabolic syndrome].

AIM: To assess effect of combined antihypertensive and lipid lowering therapy on main characteristics of metabolic syndrome and total coronary risk. MATERIAL: Seventy five patients with metabolic syndrome aged 40-59 years were included into an open study with parallel groups in which the following combinations of lipid lowering and antihypertensive drugs were used for sweeksinch: atorvastatin + perindopril (n=17, group 1); simvastatin + atenolol (n=17, group 2); fenofibrate + atenolol (n=21, group 3), and simvastatin + indapamide (n=20, group 4). Systolic and diastolic blood pressures (BP), blood serum concentrations of total cholesterol (CH), low density lipoprotein (LDL) and high density lipoprotein (HDL) CH, glucose and immunoreactive insulin were measured before and after treatment. Total coronary risk was calculated according to the PROCAM model. RESULTS: Treatment was associated with decreases of systolic and diastolic BP (from 11% in group 1 to 18,4% in group 2), lowering of total CH (by one third in groups 1 and 2, by 20% in groups 3 and 4), and triglycerides (by 2 times in group 3 and by 7-21% in other groups). Increases of HDL CH were observed in groups 2-4. There were no significant changes of markers of insulin resistance. Baseline total coronary risk was high (37%). Treatment was accompanied with lowering of total risk by 57.4-70%. CONCLUSION: Combined antihypertensive and lipid lowering therapy leads to pronounced lowering of high coronary risk in metabolic syndrome.

Adult↗
PubMed2003

[Relationship between changes of endothelial vasodilator function, vascular and cardiac structure and derangements of blood pressure 24-hour profile].

AIM: To assess relationship between 24-hour blood pressure (BP) rhythm and structural and functional state of the heart and blood vessels. MATERIAL AND METHODS: Echocardiography, sonography of carotid artery intima-media, and assessment of endothelium dependent (flow mediated) and endothelium independent (nitroglycerine) brachial artery vasodilatation were used in the study of 83 patients with stage I-II essential hypertension (mean age 49.2+/-6.2 years). Seventy four patients received indapamide and enalapril for 24 weeks. RESULTS: According to results of 24-hour BP monitoring the patients were divided into 2 groups with normal (dippers) and abnormal (non-dippers) BP rhythm. Non-dippers compared with dippers had more pronounced lowering of endothelium-dependent autoregulation of arterial tone, bigger left ventricular mass thicker carotid artery wall. Linear correlation was found between changes of 24-hour BP rhythm and structural and functional parameters of the heart and vessels. More pronounced regression of their derangements occurred during antihypertensive therapy in those patients in whom normalization of 24-hour rhythm was achieved.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

[Evaluation of the antihypertensive efficacy and tolerability of fixed very low-dose perindopril/indapamid combination in patients with mild to moderate hypertension. Results of a Czech and Slovak multicentric study].

AIM OF THE STUDY: To evaluate the efficacy and tolerability of fixed, low-dose perindopril (2 mg) and indapamide (0.625 mg) combination in patients with mild to moderate hypertension. Secondary aim of the study was to assess the influence of this combination on basic echocardiographic parameters. GROUP OF PATIENTS AND METHODS: 112 patients (57% men, 43 women, mean age 52 +/- 13 years) with newly diagnosed mild to moderate hypertension, without left ventricular dysfunction. 55% of patients had at least one risk factor for coronary artery disease. The following parameters were studied: BMI, sitting and upright casual blood pressure, heart rate, main echocardiographic parameters and basal laboratory tests. RESULTS: Perindopril/indapamide treatment led already after 4 weeks to a significant blood (BP) reduction with most prominent BP differences at the end of the study (sitting BP 130 +/- 10/84 +/- 6 mm Hg vs. 153 +/- 10/97 +/- 5 mm Hg before the treatment). Normalisation of the BP was achieved in 76% of the hypertensives. Good response to treatment (decrease in systolic BP > or = 20 mm Hg and/or decrease in diastolic BP > or = 10 mm Hg) was reported in another 13% patients. Perindopril/indapamid treatment led to a significant decrease in interventricular thickness (10.7 vs. 10.2, P < 0.01) and to the improvement in the left ventricle diastolic function (E/A 1.06 vs. 1,14, P < 0.04). No significant changes in basal laboratory tests were reported during the study. Mild side effects were observed in a few patients. CONCLUSION: Fixed, low-dose perindopril/indapamide combination is a new and potent antihypertensive compound with very good tolerability without a negative influence on metabolic parameters. Perindopril/indapamide treatment resulted in the improvement of diastolic function and in the regression of the left ventricle mass.

Antihypertensive Agents↗
PubMed2004

[The drug of the month: a new antihypertensive association: Preterax, low doses of ACE inhibitor and thiazide in the same pill].

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.

Drug Combinations↗
PubMed2005

[Comparison of noliprel and caposide efficacy in patients with arterial hypertension of high risk].

AIM: To compare clinical efficacy and tolerance of fixed combinations of perindopril and indapamide (noliprel), capoten+hydrochlorotiaside (caposide) in arterial hypertension stage I-II of high and very high risk which failed prior monotherapy. MATERIAL AND METHODS: A blind randomized trial in parallel groups recruited 40 patients (20 patients each). The patients received 1 tablet a day noliprel (2 mg/0.625 mg) or caposide (50 mg/25 mg) for 6 months. Target pressure patients were counted. Speed of the pulse wave, blood lipids and electrolytes, left ventricular myocardium posterior wall thickness were estimated. RESULTS: By antihypertensive efficacy and ability to reduce left ventricular hypertrophy and to improve arterial elasticity, low-dose fixed combination (noliprel) was not inferior to caposide (high-dose fixed combination) while by T/P noliprel was more effective than caposide, it lowered cholesterol more but potassium level--less. CONCLUSION: Noliprel has the the same with caposide antihypertensive efficacy and ability to diminish LVH. It has benefits by action on lipid and electrolyte indices.

Antihypertensive Agents↗