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PubMed2004

Twenty-four-hour ambulatory blood pressure monitoring efficacy of perindopril/indapamide first-line combination in hypertensive patients: the REASON study.

BACKGROUND: Circadian blood pressure (BP) measurements provide more information on hypertensive complications than office BP measurements. The purpose of this study was to analyze the efficacy of the first-line combination of perindopril 2 mg plus indapamide 0.625 mg versus atenolol 50 mg on BP parameters and variability over 24 h in patients with hypertension. METHODS: A double-blind, randomized, controlled, 12-month study comparing perindopril/indapamide and atenolol was performed in 201 patients (age 55.0 years) with uncomplicated sustained essential hypertension. Ambulatory BP measurements (ABPM) were done every 15 min over 24 h. RESULTS: After 1 year of treatment, the decrease in systolic BP was significantly greater for perindopril/indapamide than for atenolol during the entire 24-h period (-13.8 v -9.2 mm Hg), the daytime and the nighttime periods (P <.01). Diastolic blood pressure (DBP) variations were comparable for the two groups (-7.2 v -8.3 mm Hg, NS). Pulse pressure (PP) reduction was also significantly greater for perindopril/indapamide than for atenolol (for the whole 24 h, -6.6 v -0.9 mm Hg, P <.001). The through to peak (T/P) BP ratio and the smoothness index were comparable in the two groups for DBP. For systolic blood pressure (SBP), higher values of the T/P ratio (0.80 v 0.59) and the smoothness index (1.45 v 0.98; P <.02) were achieved for the perindopril/indapamide combination than for atenolol. CONCLUSIONS: The perindopril/indapamide first-line combination decreased SBP and PP more effectively than atenolol. Moreover, the BP control effect was smooth and consistent throughout the 24-h dosing interval and BP reduction variability was lower than the one induced by atenolol.

Adrenergic beta-Antagonists↗
PubMed2004

Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol.

OBJECTIVES: The goal of this study was to determine if a low-dose combination of the angiotensin-converting enzyme inhibitor perindopril (Per) and the diuretic indapamide (Ind) reduces central (thoracic aorta, carotid artery) as well as brachial systolic blood pressure (SBP) more than the beta-blocker atenolol and to determine the hemodynamic factors influencing independently brachial and central SBP: pulse wave velocity (PWV) and pattern of wave reflections. BACKGROUND: In high cardiovascular risk populations, angiotensin blockade improves survival without affecting brachial SBP and diastolic blood pressure (DBP). Whether central SBP, which is physiologically lower than brachial SBP, is significantly reduced has never been investigated. METHODS: This study was a double-blind randomized trial for one year in patients with essential hypertension. RESULTS: For a similar DBP reduction, Per/Ind decreased SBP significantly more than atenolol, with a more pronounced reduction for central than for brachial SBP. After one year, the difference between brachial and central SBP was maintained by Per/Ind (8.28 +/- 1.53 mm Hg) and significantly attenuated by atenolol (0.29 +/- 1.61 mm Hg). Under atenolol, the principal factor modulating SBP reduction was mean blood pressure. Under Per/Ind, this parameter played a minor role, and the central SBP reduction implied a major role for disturbed PWV and wave reflections. CONCLUSIONS: Under Per/Ind, but not atenolol, normalization of brachial SBP is achieved with a significantly greater reduction of central SBP. This hemodynamic profile reflects changes of wave reflections issued from distal arterial and arteriolar territory, where Per/Ind, but not atenolol, is known to improve vessel wall structure.

Antihypertensive Agents↗
PubMed2003

Effect of the location of hydrogen abstraction on the fragmentation of diuretics in negative electrospray ionization mass spectrometry.

The diuretic agents bumetanide, xipamide, indapamide, and related compounds were investigated in order to determine the effect of different ionization sites on their collisionally activated dissociation and the corresponding fragmentation pathways. Therefore, analytes were selectively alkylated, and structural analogues as well as deuterium labeled compounds synthesized, which contain a reduced number of ionizable hydrogen atoms. Thus, specific hydrogen abstractions and their correlated dissociation routes of the negatively charged molecules were eliminated, providing evidence for the influence of the location of ionization on product ion spectra. Fragment ions such as m/z 78 indicate ionization at the commonly present sulfamoyl residue of diuretics but does not exclude additional ionization sites. Product ion spectra of the investigated diuretic agents proved to be composed by fragmentations initiated from different hydrogen abstractions. Moreover, the generation of radical anions by collision-activated dissociation of even-electron precursor ions was observed, the generation of which is discussed by proposed fragmentation pathways.

Bumetanide↗
PubMed1998

PROGRESS: Perindopril pROtection aGainst REcurrent Stroke Study: status in March 1997. PROGRESS Management Committee.

MAIN OBJECTIVE: The study has been designed to assess the efficacy of blood pressure (BP) reduction in the prevention of stroke in patients with a history of ischaemic stroke, haemorrhagic stroke, or transient ischaemic attack. STUDY DESIGN: A randomised, double-blind, placebo-controlled, international, multicentre trial of the angiotensin-converting enzyme (ACE) inhibitor perindopril, alone or in combination with the diuretic indapamide, in the secondary prevention of stroke and other major cardiovascular events. METHODOLOGY: A total of 6000 normotensive or hypertensive patients with a history of stroke or transient cerebral ischaemia within the previous 5 years will be included in the study. The study is being conducted in over 160 centres located in seven regions: Australia and New Zealand; The People's Republic of China; France and Belgium; Italy; Japan; Sweden; and the United Kingdom. The primary study outcome is the total number of strokes defined by WHO criteria. Secondary outcomes include fatal and disabling strokes, total number of cardiovascular events and deaths, cognitive function, disability, and dependency. A minimum of 4 years' follow-up is planned. RESULTS: By 27 March 1997, 173 local clinical centres had been registered in seven regions. A total of 5268 patients (64% with a history of hypertension or baseline BPs above 95 mm Hg [diastolic] or 160 mm Hg [systolic]) had been randomly assigned to active treatment or placebo. After 6 months' follow-up the difference in BP between treatment and control groups was 10.2/4.5 mm Hg (systolic/diastolic). Sixty-three strokes (two fatal) and 20 myocardial infarctions (four fatal) had been recorded. CONCLUSIONS: The viability of the study is now assured, with almost 90% of 6000 patients recruited. ACE therapy with perindopril is well tolerated in the studied population. The BP differences between control and treatment groups and the event rates recorded to date suggest that the study will achieve its primary objectives.

Aged↗
PubMed1999

Effectiveness and metabolic effects of perindopril and diuretics combination in primary hypertension.

The effectiveness as well as the metabolic effects of the combination of diuretics [hydrochlorothiazide (HCT) vs indapamide (IND)] and perindopril (P) in 14 patients (7 male, 7 female) aged 37-62 years with mild idiopathic hypertension were studied. Following a 4-week wash-out period and a 4-week period of monotherapy with P (4 mg/daily), IND (2.5 mg/daily) or HCT (25 mg/daily) was added for 4 weeks. Selection of the diuretic agent was random. Following a 4-week wash-out period from the diuretic, in which only P was given, the alternative diuretic was administered for another period of 4 weeks. P decreased blood pressure levels significantly. However, the drug was more efficacious in patients with higher plasma renin activity (PRA). Combination treatment induced an additional decrease in the blood pressure levels, mainly in patients with lower PRA. The combination of P + HCT was more effective than the combination P + IND. The addition of either HCT or IND evoked a small but statistically significant increase in serum glucose levels while fasting as well as during the 75 g oral glucose challenge. However, insulin levels did not change significantly during the study. Small but not statistically significant changes in serum electrolytes and lipid parameters were observed during the various phases of the study, while a statistically significant increase in the serum uric acid was noticed when the combination P + HCT was given. We conclude: (1) P in small doses is an effective and safe antihypertensive agent, (2) PRA has a predictive value in determining the effectiveness of P treatment, (3) the combination of P with small doses of HCT or IND is more efficacious than P alone, (4) the combination treatment has adverse effects in the carbohydrate tolerance, while there are not significant changes in serum electrolyte and lipid parameters.

Adult↗
PubMed1994

[Severe pancytopenia in old age after 12-month ACE inhibitor therapy].

A sprightly 79-year-old woman was treated for high blood pressure with indapamide (2.5 mg/day) and the angiotensin converting enzyme (ACE) inhibitor lisinopril (5 mg/day). About 12 months after starting treatment a blood count carried out because of a syncopal attack revealed pancytopenia (haemoglobin 3.3 g/dl, erythrocytes 1.0 x 10(6)/microliters, leucocytes 1100/microliters, platelets 8000/microliters). Until then the blood count had been unremarkable. The bone marrow showed severe hypoplasia of all three cell lines with reactive plasmocytosis. Malignant cells were not present. The patient received a total of nine units of erythrocytes and seven units of platelets. Her care included reverse barrier nursing and antibiotic treatment. She was also given high dose steroid therapy (methylprednisone up to 150 mg/day) and granulocyte colony stimulating factor (filgrastim 300 micrograms/day subcutaneously for 25 days), and after a latent period of several weeks juvenile myeloid precursors reappeared in the blood. Before discharge from hospital the results rose to subnormal levels without further transfusions (haemoglobin 8.5/dl, erythrocytes 3.1 x 10(6)/microliters, leucocytes 3900/microliters, platelets 21.000/microliters). In the bone marrow, all three cell lines were beginning to recover. The final diagnosis was incompletely reversible pancytopenia resulting from secondary aplastic anaemia during ACE inhibitor therapy.

Aged↗
PubMed2004

Reductions in the risks of recurrent stroke in patients with and without diabetes: the PROGRESS Trial.

BACKGROUND: Analyses of the risks of stroke were conducted for subjects with and without diabetes, participating in a randomized, double-blind, placebo-controlled trial of a perindopril-based blood pressure lowering regimen in 6105 people with prior stroke or transient ischaemic attack (TIA), followed for a median of 3.9 years. FINDINGS: Seven hundred and sixty-one patients had diabetes at baseline. Diabetes increased the risk of recurrent stroke by 35% (95% CI 10-65%) principally through an effect on ischaemic stroke (1.53, 95% CI 1.23-1.90). Active treatment reduced blood pressure by 9.5/4.6 mmHg in patients with diabetes and by 8.9/3.9 mmHg in patients without diabetes. The proportional risk reductions achieved for stroke in patients with diabetes, 38% (95% CI 8-58%), and patients without diabetes, 28% (95% CI 16-39%), were not significantly different (p homogeneity = 0.5). The absolute reduction in the risk of recurrent stroke in the patients with diabetes was equivalent to one stroke avoided among every 16 (95% CI 9-111) patients treated for 5 years. CONCLUSIONS: Diabetes is an important risk factor for stroke in patients with established cerebrovascular disease. Treatment with the ACE inhibitor perindopril with discretionary use of the diuretic indapamide produced reductions in the risk of recurrent stroke in patients with diabetes that were at least as great as those achieved in patients without diabetes.

Aged↗
PubMed1998

Acute hyponatremic encephalopathy after a cerebrovascular accident.

A 66-year-old hypertensive male with acute intracerebral hemorrhage developed acute hyponatremic coma 3 days after the addition of enalapril and a combination of amiloride and a thiazide diuretic to his hypotensive regimen. The patient recovered consciousness and serum sodium normalized 2 days after fluid restriction and withdrawal of both medications. Three weeks later, upon inadvertent reinstitution of enalapril and indapamide, severe hyponatremic encephalopathy promptly recurred; recovery was again rapid following fluid restriction and withdrawal of both medications. This temporal relationship establishes the thiazide diuretic or the angiotensin converting enzyme inhibitor or both as the cause of the profound symptomatic hyponatremia in this patient. Results of simultaneous serum and urine osmolality assays on several occasions were consistent with a decrease in free water clearance, a result of either increased antidiuretic hormone (ADH) secretion or potentiation of its peripheral action, and thiazide-induced natriuresis. The use of a thiazide diuretic in the presence of either of these aberrations of ADH homeostasis most likely explains the profound and rapid development of hyponatremia. Drug-induced disturbances in serum osmolality are a potentially reversible cause of deterioration of the mental state in a patient with an acute cerebrovascular accident.

Aged↗
PubMed1996

Chinese contribution to trials on antihypertensive therapy.

LACK OF TRIAL DATA ON NEW ANTIHYPERTENSIVE AGENTS: The present debate concerning the use of new classes of antihypertensive agents in general and calcium antagonists in particular, is due to the fact that for most of the agents, there is a lack of data from major clinical trials with cardiovascular outcomes. CONTRIBUTION OF CHINESE CLINICAL TRIAL DATA: The present review summarizes and qualifies the prospective clinical trial data obtained in China which were performed with calcium antagonists and indapamide. These results need to be reviewed critically for their weaknesses as well as strengths, so that the data can be used to improve present knowledge of antihypertensive therapy.

Antihypertensive Agents↗
PubMed2000

Long-term efficacy of a new, fixed, very-low-dose angiotensin-converting enzyme-inhibitor/diuretic combination as first-line therapy in elderly hypertensive patients.

OBJECTIVE: To determine the long-term efficacy and safety of a fixed, very-low-dose tablet combining one-half the standard dose of perindopril with one-quarter the standard dose of indapamide as first-line treatment in elderly patients. DESIGN: Double-blind, randomized, placebo-controlled study in an outpatient setting. PATIENTS AND INTERVENTIONS: Following a single-blind, placebo run-in period of 4 weeks, patients [65-85 years, with mild-to-moderate essential hypertension or isolated systolic hypertension (ISH)] were randomized to receive one tablet of perindopril 2 mg/indapamide 0.625 mg (Per/ Ind) (n=193) or placebo (n=190), daily for 12 weeks. After this first 12-week period, all patients on Per/Ind (n=138) and patients responding to placebo (n=61) were maintained on their previous regimen for a further 48 weeks. Patients in the placebo group whose blood pressure was not normalized, were switched to Per/Ind (n=60). MAIN OUTCOME MEASURE: The primary endpoint was the proportion of patients with blood pressure that normalized between weeks 0 and 60. RESULTS: After 1 year of treatment (intention-to-treat) supine systolic and diastolic blood pressure decreased by 23.0 +/- 15.3 mmHg and 13.3 +/- 94 mmHg with Per/Ind (n=253: 193 from randomized Per/Ind group and 60 from the placebo group switched at week 12). The mean decreases in systolic blood pressure were similar in essential hypertension and ISH (systolic blood pressure 23.2 versus 22.7 mmHg, respectively). Per/Ind treatment (n=253) achieved an initial normalization of blood pressure in 96.2% [95% confidence interval (CI) 93.6-98.9%; Kaplan-Meier estimate] of Per/Ind-treated patients; 79.8% (95% CI 74.1-85.5%) of these maintained a normalized blood pressure throughout the 1 -year follow-up. The incidence of adverse events was similarly low in the placebo and active therapy groups. Efficacy and safety results for the over 75 years subgroup were similar to those for the younger elderly subjects CONCLUSIONS: The fixed, very low-dose combination of perindopril 2 mg/indapamide 0.625 mg results in sustained blood pressure control when used as first line treatment of elderly hypertensive patients over 1-year, and is well-tolerated.

Aged↗
PubMed2001

Pulse wave velocity as endpoint in large-scale intervention trial. The Complior study. Scientific, Quality Control, Coordination and Investigation Committees of the Complior Study.

OBJECTIVE: To evaluate the ability of an antihypertensive therapy to improve arterial stiffness as assessed by aortic pulse wave velocity (PWV) in a large population of hypertensive patients. SETTING: Sixty-nine healthcare centres, private and institutional (19 countries). PATIENTS: Subjects aged 18-79 years, with essential hypertension. A total of 2,187 patients were enrolled; 1,703 (52% male) completed the study: mean age = 50 +/- 12 years; mean baseline systolic/diastolic blood pressure (S/D BP) = 158 +/- 15/98 +/- 7 mmHg; mean baseline carotid-femoral PWV = 11.6 +/- 2.4 m/s. INTERVENTIONS: Patients were treated for 6 months, starting with perindopril (angiotensin converting enzyme (ACE) inhibitor) 4 mg once daily (OD), increased to 8 mg OD, and combined to diuretic (indapamide 2.5 mg OD) if BP was uncontrolled (> 140/90 mmHg). RESULTS: It was feasible to measure carotid-femoral PWV using the automatic device Complior at inclusion, 2 and 6 months, along with conventional BP assessments in a population of 1,703 patients. Significant decreases (P < 0.001) in BP (systolic: -23.7 +/- 16.8, diastolic: -14.6 +/- 10 mmHg), and carotid-femoral PWV (-1.1 +/- 1.4 m/s) were obtained at 2 and 6 months. CONCLUSIONS: The Complior Study is the first study to show the feasibility of a large-scale intervention trial using PWV as the endpoint in hypertensive patients. Adequate results may be obtained using an automatic device and rigorous criteria for assessment. A long-term controlled intervention study is needed to confirm the results of the present uncontrolled trial.

Adult↗
PubMed2003

Regression of left ventricular hypertrophy with echocardiography: some lessons from the LIVE study.

OBJECTIVE: Large trials on left ventricular hypertrophy (LVH) regression are indispensable to allow accurate evaluation of the different classes of treatments. Such a trial, the LIVE study, gave us the opportunity to examine the influence of the mode of reading of the echo tracings on results and to underline the value of two initial recordings performed at entry. METHODS: The LIVE study was designed to compare 1.5 mg indapamide SR with 20 mg enalapril on the regression of LVH evaluated echocardiographically. M-mode tracings of the left ventricle were performed at selection and after a 2 week placebo run-in. Recordings were read by investigators and by three experts all through the study, and finally read again by the three experts blind to treatment and sequence. RESULTS: The two initial examinations produced an estimate of the reproducibility of the measurement of the left ventricular mass (LVM) that can be proposed as an indicator of overall quality provided no patients are excluded. The standard deviation of the differences between these two estimates of LVM was 52 g. These two examinations may also help quantify regression to the mean, which was not significant for the whole group. Knowledge of the sequence of examinations overestimates the change in LVM with treatment, as shown by comparison of measurements carried out during quality control with the measurements made blind (-19 +/- 52 versus -6 +/- 53 g, P <0.01). CONCLUSIONS: The comparison of two initial echoes at entry allow one to define a quality criteria for such trials and to quantify a possible regression to the mean. The reading of recordings with knowledge of sequence significantly overestimates LVM variations on treatment.

Antihypertensive Agents↗
PubMed2003

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

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

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Very-low-dose combination: a first-line choice for the treatment of hypertension?

Essential hypertension is a very heterogeneous disease and different pressor mechanisms might interact to increase blood pressure. It is therefore not surprising that antihypertensive drugs given as monotherapies normalize blood pressure in only a proportion of hypertensive patients. This is, for instance, the case for diuretics, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1) receptor antagonists administered as single agents. The rationale for combining antihypertensive agents relates in part to the concept that the blood pressure-decreasing effect may be enhanced when two classes are coadministered. Also, combination treatment serves to counteract the counter-regulatory mechanisms that are triggered whenever pharmacologic intervention is initiated and act to limit the efficacy of the antihypertensive medication. For example, the compensatory increase in renin secretion induced by sodium depletion may become the predominant factor sustaining high blood pressure. Simultaneous blockade of the renin-angiotensin system, with either an ACE inhibitor or an AT1 receptor blocker, makes this compensatory hyper-reninaemia ineffective and allows maximum benefit from sodium depletion. The increased effectiveness obtained by combining a blocker of the renin-angiotensin system with a low dose of a diuretic is not obtained at the expense of reduced tolerability compared with the individual components administered alone. Fixed very-low-dose combinations containing an ACE inhibitor or an AT1 receptor blocker and a diuretic are therefore likely to become increasingly used, not only as second-line therapy, but also as first-line treatment. This is the case, for instance, for the fixed very-low-dose combination of the ACE inhibitor perindopril (2 mg) and the diuretic indapamide (0.625 mg), as this preparation is very effective in decreasing blood pressure while maintaining a tolerability that is similar to that of placebo.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Comparison of the effect of diuretics on carotid blood flow in stroke patients.

OBJECTIVES: Indapamide (IND) and bendroflumethiazide (BDZ) are both widely used in the management of blood pressure after stroke. There are theoretical reasons why these agents may differ with regard to their cardiovascular effects. We compared the effect of these agents on blood pressure and cerebral blood flow in a group of stroke patients. METHODS: In a prospective, randomized, double-blinded study we investigated the effect of 28 days' treatment with BDZ 2.5 mg od or IND 2.5 mg od on blood pressure and cerebral blood flow in a group patients with recent first-ever ischemic stroke. Using extracranial carotid and transcranial ultrasound we assessed carotid blood flow and intracranial hemodynamics. RESULTS: All data are expressed as mean (SD). Twenty-five patients completed the protocol (age 68.8 +/- 10.6 y). Groups I (IND) and B (BDZ) comprised 13 and 12 patients, respectively. Groups were well matched for demography and baseline characteristics. Percent change in mean arterial pressure reduction from baseline was (I = -14.7 +/- 12.5, P < 0.001 vs. B = -7.7 +/- 9.16 mm Hg, P = 0.02). There was a trend toward increased carotid blood flow in both groups (I = +10% +/- 47, P = 0.4 vs. B = +33% +/- 47, P = 0.12). No significant change in middle cerebral artery mean flow velocity or pulsatility index was observed. There was no significant difference between the 2 drugs with regard to change in blood pressure (95% confidence interval for difference -2.5 to 16.3 mm Hg, P = 0.14) or carotid blood flow (95% confidence interval for difference -58 to 27 mL/s, P = 0.45). CONCLUSIONS: Both diuretics reduced blood pressure to a similar and significant degree. There was no evidence of an adverse effect on cerebral blood flow or intracranial hemodynamics induced by either agent. No significant difference between the effect of IND and BDZ was observed.

Adult↗
PubMed2004

Selective reduction of cardiac mass and central blood pressure on low-dose combination perindopril/indapamide in hypertensive subjects.

OBJECTIVE: In hypertension, blockade of the renin-angiotensin system reduces left ventricular mass (LVM) independently of brachial systolic (S), diastolic (D), and mean (M) blood pressure (BP). From central to peripheral arteries, MBP and DBP are practically unchanged, whereas SBP and pulse pressure (PP) increase significantly. The objective was to determine whether changes in LVM under drug treatment was preferentially associated with changes in central or brachial SBP and PP. DESIGN: A substudy of 146 subjects was selected from 469 hypertensive patients submitted to a double-blind randomized trial comparing the combination of perindopril (2 mg; Per) and indapamide (0.625 mg; Ind) with atenolol (50 mg, one tablet per day). MAIN OUTCOME MEASURES: Before and after 1 year of treatment: LVM (echocardiography) in 146 subjects and, in 52 of them, central (carotid) BP and timing of wave reflections (tonometry). RESULTS: LVM changes were significantly associated with antihypertensive treatment, with lower LVM with Per/Ind than with atenolol. Changes in SBP and PP, but not in MBP and DBP, were more significantly associated with Per/Ind than with atenolol, with more pronounced effects using central than brachial measurements, and a longer delay in central return of wave reflections under Per/Ind. In the sampling of 52 patients with tonometry, the change in LVM between the two drug regimens was significantly linked to central, but not brachial, PP change. CONCLUSIONS: This observational study shows a lower LVM under Per/Ind than under atenolol. The greater change in LVM on Per/Ind was linked to central and not brachial blood pressure.

Adult↗
PubMed2006

Hypertension: which aspects of hypertension should we impact on and how?

Cardiovascular complications may, to a large extent, be prevented by lowering blood pressure in hypertensive patients. International recommendations currently stress the importance of reaching values of below 140/90 mmHg in each patient or even lower in the case of concomitant diabetes or renal impairment. It is currently considered crucial to control the systolic pressure as well as the diastolic pressure, in particular because the relationship between cardiovascular risk and blood pressure is closer for the systolic than the diastolic value. An increase in systolic pressure is in itself a sign of the stiffening of the arterial tree. In most patients, the target pressure may only be reached by combining several different antihypertensive agents. In the STRATHE Study, a greater antihypertensive efficacy, in particular on systolic pressure, was obtained by instituting treatment with a fixed low-dose combination of an angiotensin-converting enzyme inhibitor (perindopril) and a diuretic (indapamide), in comparison with other therapeutic strategies based on single-agent therapy. Fixed-dose antihypertensive combinations have now become a validated option for initiating antihypertensive treatment.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

Rationale and methodology of monitoring ambulatory blood pressure and arterial compliance in the Hypertension in the Very Elderly Trial.

OBJECTIVE: This article describes the rationale and methodology for the monitoring of ambulatory blood pressure and arterial compliance in hypertensive patients aged 80 years and above. This is a side project of the Hypertension in the Very Elderly Trial. METHODS: The hypertension in the Very Elderly Trial is a multicentre, double-blind, randomized, placebo-controlled trial aiming to investigate the effect of active treatment on cardiovascular and other outcomes in hypertensive patients aged 80 years or more. Patients are randomized to placebo or active treatment starting with the diuretic indapamide and adding the angiotensin-converting enzyme inhibitor perindopril if required. This study has completed a pilot trial and the main trial is now underway. Six hundred patients will have two ABPM recordings, the first at baseline and the second a year after randomization. Arterial compliance is measured using the Q wave (electrocardiogram) to Korotkoff diastole sound interval. RESULTS: Baseline characteristics for the first 50 patients recruited are presented. CONCLUSION: This side project will allow the investigation of 24-h ambulatory measures of blood pressure and arterial compliance as predictors of cerebrovascular and cardiovascular events in the very elderly. The project will also allow the investigation of the blood pressure and vascular compliance profiles in the very elderly and their changes with posture. The association between these measurements and mortality and morbidity in this age group will be addressed.

Aged, 80 and over↗