eprosartan and Stroke

Hypertension is a common condition associated with considerable morbidity and mortality. Antihypertensive drugs reduce the risk of cardiovascular and cerebrovascular events, and may also be associated with reductions in cognitive decline. Eprosartan is an angiotensin II type 1 receptor antagonist with a unique dual mechanism of action that is approved for the treatment of essential hypertension. In clinical trials, eprosartan has been shown to significantly reduce systolic blood pressure and to be associated with significant reductions in pulse pressure in elderly patients with isolated systolic hypertension. Data suggest that blood pressure reductions achieved with eprosartan in elderly hypertensive patients are also associated with improvements in cognitive function. Eprosartan compares favorably with other classes of antihypertensive agents in terms of reductions in mortality, cardiovascular and cerebrovascular events, and stroke recurrence. Evidence suggests that eprosartan may represent a useful addition to combination drug strategies for the management of hypertensive patients with elevated cardiovascular and cerebrovascular risk.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Blood Pressure; Blood Pressure Determination; Cardiovascular Diseases; Cognition Disorders; Female; Humans; Hypertension; Imidazoles; Male; Sensitivity and Specificity; Severity of Illness Index; Stroke; Survival Analysis; Systole; Thiophenes; Treatment Outcome

Given the ageing population, dementia is an ever-increasing health burden. A positive correlation between cognitive decline or dementia and blood pressure levels has been indicated. There is, however, conflicting evidence over the definitive link between the use of antihypertensives and the subsequent reduction of cognitive decline. The specific use of angiotensin II receptor blockers (ARBs) in preventing vascular dementia has been investigated with eprosartan treatment. In animal studies utilising stroke-prone rats, eprosartan has been shown to reduce end-organ damage of the heart and kidneys in a study assessing cardiomyopathy and renal failure. The Morbidity and mortality after Stroke, Eprosartan compared with nitrendipine for Secondary prevention (MOSES) study, assessing 1405 patients, has shown the cerebroprotective effects of eprosartan compared with the calcium channel blocker nitrendipine. In this study, however, no change in cognitive function, as assessed by the mini-mental status examination (MMSE) score, was seen between the treatment groups. The Observational Study on Cognitive function And systolic blood pressure Reduction (OSCAR) trial, including more than 60,000 hypertensive patients, also assessed the ability of eprosartan to alter the MMSE score. In contrast to the MOSES trial, preliminary data from 10,000 patients after 6 months of treatment identified a decrease in blood pressure alongside a significant increase in MMSE score. Specific subpopulations within this study, including the elderly, patients with higher initial systolic blood pressure and patients with a body mass index (BMI) of 25-30 kg/m2 showed the greatest change in MMSE score. These data indicate an association with blood pressure reduction and improvement of cognitive function with eprosartan treatment.

Topics: Acrylates; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Animals; Cognition Disorders; Dementia, Vascular; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Neuropsychological Tests; Rats; Stroke; Thiophenes

Angiotensin (AT) II and noradrenaline play major roles in hypertension, stroke and coronary heart disease, which are themselves interlinked. Harmful effects of AT II are not blocked solely by angiotensin-converting enzyme inhibitors, as it is now evident that AT II is generated by other enzymes such as chymase. Angiotensin II also stimulates noradrenaline release modulated by presynaptic receptors on sympathetic nerves. Numerous studies have defined the action of the AT II type 1 receptor blocker (ARB) eprosartan as controlling noradrenergic and adrenergic effects, resulting from actions on the renin-angiotensin-aldosterone system and the sympathetic nervous system. Clinical studies have been carried out to assess the effects of ARBs on morbidity and mortality. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial compared the effects of valsartan and the calcium channel blocker (CCB) amlodipine in over 15,000 patients at high risk of a cardiac event. Results showed that blood pressure was reduced by both treatments and cardiac mortality/morbidity was similar in both groups. By contrast, the Morbidity and mortality after Stroke, Eprosartan compared with nitrendipine for Secondary prevention (MOSES) study (n = 1405) generated results which differed from the VALUE study, in that blood pressure was reduced by both eprosartan and nitrendipine, but eprosartan reduced all cardiovascular and cerebrovascular events to a greater extent than nitrendipine. It is also possible that any delayed clinical benefit of eprosartan could be due to reverse cardiac remodelling. Eprosartan, by blocking AT II receptors, reducing noradrenaline release and blocking catecholamine actions, may, therefore, provide greater protection against vascular events than CCBs or other ARBs.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Catecholamines; Humans; Hypertension; Imidazoles; Norepinephrine; Stroke; Tetrazoles; Thiophenes; Valine; Valsartan

Hypertension is the most important cardiovascular risk factor for stroke. Blood pressure reduction by antihypertensive treatment is clearly efficacious in the prevention of stroke (both primary and secondary), although no clear differences have yet been observed between antihypertensive drug classes. However, a recent study reported the clear superiority of the angiotensin-receptor blocker eprosartan over the calcium channel blocker nitrendipine in cardiovascular protection of hypertensive patients with a previous stroke. Comparative studies using angiotensin-receptor blockers have also suggested the superiority of this class of drugs on primary stroke prevention. This effect may be linked to their beneficial actions on left ventricular hypertrophy, atrial enlargement, and supraventricular arrhythmias, endothelial dysfunction, inflammation, and remodelling, as well as a direct neuroprotective effect mediated through the stimulation of the angiotensin II type-2 receptor. In addition, a sympathoinhibition observed with the renin-angiotensin system blockers and particularly demonstrated with eprosartan, may help to explain the better cardiovascular and cerebrovascular protection in comparison with the calcium antagonist nitrendipine.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Endothelium, Vascular; Humans; Hypertension; Imidazoles; Neuroprotective Agents; Nitrendipine; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Research Design; Risk Factors; Stroke; Thiophenes; Treatment Outcome

Given the ageing population, dementia is an ever-increasing health burden. A positive correlation between cognitive decline or dementia and blood pressure levels has been indicated. There is, however, conflicting evidence over the definitive link between the use of antihypertensives and the subsequent reduction of cognitive decline. The specific use of angiotensin II receptor blockers (ARBs) in preventing vascular dementia has been investigated with eprosartan treatment. In animal studies utilising stroke-prone rats, eprosartan has been shown to reduce end-organ damage of the heart and kidneys in a study assessing cardiomyopathy and renal failure. The Morbidity and mortality after Stroke, Eprosartan compared with nitrendipine for Secondary prevention (MOSES) study, assessing 1405 patients, has shown the cerebroprotective effects of eprosartan compared with the calcium channel blocker nitrendipine. In this study, however, no change in cognitive function, as assessed by the mini-mental status examination (MMSE) score, was seen between the treatment groups. The Observational Study on Cognitive function And systolic blood pressure Reduction (OSCAR) trial, including more than 60,000 hypertensive patients, also assessed the ability of eprosartan to alter the MMSE score. In contrast to the MOSES trial, preliminary data from 10,000 patients after 6 months of treatment identified a decrease in blood pressure alongside a significant increase in MMSE score. Specific subpopulations within this study, including the elderly, patients with higher initial systolic blood pressure and patients with a body mass index (BMI) of 25-30 kg/m2 showed the greatest change in MMSE score. These data indicate an association with blood pressure reduction and improvement of cognitive function with eprosartan treatment.

Topics: Acrylates; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Animals; Cognition Disorders; Dementia, Vascular; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Neuropsychological Tests; Rats; Stroke; Thiophenes

Topics: Acrylates; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Data Interpretation, Statistical; Diuretics; Humans; Imidazoles; Internal Medicine; Ischemic Attack, Transient; Morbidity; Neurology; Nitrendipine; Prospective Studies; Stroke; Thiophenes

Topics: Acrylates; Amlodipine; Antihypertensive Agents; Calcium Channel Blockers; Data Interpretation, Statistical; Humans; Imidazoles; Ischemic Attack, Transient; Nitrendipine; Research Design; Risk Factors; Stroke; Thiophenes

In hypertensive stroke patients, for the same level of blood pressure control, eprosartan will be more effective than nitrendipine in reducing cerebrovascular and cardiovascular morbidity and mortality.. A total of 1405 well-defined, high-risk hypertensives with cerebral event during the last 24 months (proven by cerebral computed tomography scan or nuclear magnetic resonance) were randomized to eprosartan or nitrendipine (mean follow-up 2.5 years). Primary end point was the composite of total mortality and all cardiovascular and cerebrovascular events, including all recurrent events.. Randomization was successful without significant differences in the baseline characteristics. Blood pressure was reduced to a comparable extent without any significant differences between the 2 groups during the whole study period (150.7/84 mm Hg and 152.0/87.2 mm Hg with eprosartan and nitrendipine therapy to 137.5/80.8 mm Hg and 136.0/80.2 mm Hg, respectively, confirmed by ambulatory blood pressure monitoring). Moreover, already after 3 months, normotensive mean values were achieved, and 75.5% reached values <140/90 mm Hg with the eprosartan regimen and 77.7% with the nitrendipine regimen. During follow-up, in total, 461 primary events occurred: 206 eprosartan and 255 nitrendipine (incidence density ratio [IDR], 0.79; 95% CI, 0.66 to 0.96; P=0.014). Cardiovascular events were: 77 eprosartan and 101 nitrendipine (IDR, 0.75; 95% CI, 0.55 to 1.02; P=0.06); cerebrovascular events: 102 eprosartan and134 nitrendipine (IDR, 0.75; 95% CI, 0.58 to 0.97; P=0.03).. The Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention (MOSES) study was the first to compare an angiotensin II type 1 receptor antagonist with a calcium antagonist in secondary stroke prevention. In these high-risk hypertensive stroke patients, an early normotensive and comparable blood pressure was achieved. The combined primary end point was significantly lower in the eprosartan group.

Topics: Acrylates; Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Body Mass Index; Calcium; Cardiovascular Diseases; Female; Humans; Hypertension; Imidazoles; Magnetic Resonance Spectroscopy; Male; Middle Aged; Nitrendipine; Prospective Studies; Recurrence; Risk Factors; Single-Blind Method; Sodium Chloride Symporter Inhibitors; Stroke; Thiophenes; Time Factors; Treatment Outcome

Twenty patients with stroke of hemisphere localization developed as a result of arterial hypertension were treated with eprosartan mesilat. An estimation of the drug efficacy was conducted in comparison with other hypotensive medicines (control group). Eprosartan was used in dosage 600 mg daily. The study was carried out during 12 months, along with a monitoring of the most relevant hemodynamic indices, evaluation of somatic and neurological state of the patients as well as of some neuropsychological functions and quality of life, statistical significance of the results being determined. Pronounced hypotensive effect of the drug was found both in acute and late periods of stroke. Eprosartan mesilat monotherapy was effective in 75% of the patients. The most important feature proved to be a decrease of arterial pressure variability from the first days of the treatment, less frequency of secondary strokes being detected as well.

Topics: Acrylates; Acute Disease; Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Chi-Square Distribution; Data Interpretation, Statistical; Diastole; Female; Hemodynamics; Humans; Hypertension; Imidazoles; Male; Middle Aged; Quality of Life; Recurrence; Stroke; Systole; Thiophenes; Time Factors

The renin-angiotensin and sympathetic nervous systems play critical interlinked roles in the development of left ventricular hypertrophy, fibrosis, and dysfunction. These studies investigated the hemodynamic and cardiac effects of monoblockade and coblockade of renin-angiotensin and sympathetic nervous systems. Stroke-prone spontaneously hypertensive rats (16 weeks old; male; n=12 per group) received the sympatholytic imidazoline compound, moxonidine (2.4 mg/kg per day); the angiotensin-receptor blocker eprosartan (30 mg/kg per day), separately or in combination; or saline vehicle for 8 weeks, SC, via osmotic minipumps. Blood pressure and heart rate were continuously measured by radiotelemetry. After 8 weeks, in vivo cardiac function and structure were measured by transthoracic echocardiography and a Millar conductance catheter, and the rats were then euthanized and blood and heart ventricles collected for various determinations. Compared with vehicle, the subhypotensive dose of moxonidine resulted in lower (P<0.01) heart rate, left ventricular hypertrophy, cardiomyocyte cross-sectional area, interleukin 1 beta, tumor necrosis factor-alpha, and mRNA for natriuretic peptides. Eprosartan reduced pressure (P<0.01), as well as extracellular signal-regulated kinase (ERK) 44 phosphorylation, Bax/Bcl-2, and collagen I/III, and improved left ventricular diastolic function (P<0.03). Combined treatment resulted in greater reductions in blood pressure, heart rate, left ventricular hypertrophy, collagen I/III, and inhibited inducible NO synthase and increased endothelial NO synthase phosphorylation, as well as reduced left ventricular anterior wall thickness, without altering the other parameters. Thus, in advanced hypertension complicated with cardiac fibrosis, sympathetic inhibition and angiotensin II blockade resulted in greater reduction in blood pressure and heart rate, inhibition of inflammation, and improved left ventricular pathology but did not add to the benefits of angiotensin II blockade on cardiac function.

Topics: Acrylates; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Heart Rate; Hypertension; Imidazoles; Male; Nitric Oxide Synthase Type III; Phosphorylation; Rats; Rats, Inbred SHR; Stroke; Thiophenes; Ventricular Function, Left

Hypertension control is critical to prevent stroke. With several clinical trials conducted over the last decade, it seems that the use of an angiotensin-modulating antihypertensive agent conveys benefits beyond blood pressure reduction. Currently, there is evidence supporting the use of either an angiotensin receptor blocker or an angiotensin-converting enzyme inhibitor in the primary-prevention context. However, in the secondary prevention of stroke, the choice of agent is less clear. There is evidence that intensive blood pressure reduction with a combination of an angiotensin-converting enzyme inhibitor and a diuretic can reduce stroke recurrence, but do angiotensin receptor blockers have the same ability? The Morbidity and Mortality after Stroke, Eprosartan Compared with Nitrendipine for Secondary Prevention (MOSES) trial endeavors to answer this question and strives to demonstrate the benefit of angiotensin receptor blockers in the secondary prevention of stroke.

Topics: Acrylates; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Female; Humans; Hypertension; Imidazoles; Ischemic Attack, Transient; Male; Nitrendipine; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Thiophenes

To investigate the cost-utility of eprosartan versus enalapril (primary prevention) and versus nitrendipine (secondary prevention) on the basis of head-to-head evidence from randomized controlled trials.. The HEALTH model (Health Economic Assessment of Life with Teveten for Hypertension) is an object-oriented probabilistic Monte Carlo simulation model. It combines a Framingham-based risk calculation with a systolic blood pressure approach to estimate the relative risk reduction of cardiovascular and cerebrovascular events based on recent meta-analyses. In secondary prevention, an additional risk reduction is modeled for eprosartan according to the results of the MOSES study ("Morbidity and Mortality after Stroke--Eprosartan Compared to Nitrendipine for Secondary Prevention"). Costs and utilities were derived from published estimates considering European country-specific health-care payer perspectives.. Comparing eprosartan to enalapril in a primary prevention setting the mean costs per quality adjusted life year (QALY) gained were highest in Germany (Euro 24,036) followed by Belgium (Euro 17,863), the UK (Euro 16,364), Norway (Euro 13,834), Sweden (Euro 11,691) and Spain (Euro 7918). In a secondary prevention setting (eprosartan vs. nitrendipine) the highest costs per QALY gained have been observed in Germany (Euro 9136) followed by the UK (Euro 6008), Norway (Euro 1695), Sweden (Euro 907), Spain (Euro -2054) and Belgium (Euro -5767).. Considering a Euro 30,000 willingness-to-pay threshold per QALY gained, eprosartan is cost-effective as compared to enalapril in primary prevention (patients >or=50 years old and a systolic blood pressure >or=160 mm Hg) and cost-effective as compared to nitrendipine in secondary prevention (all investigated patients).

Topics: Acrylates; Antihypertensive Agents; Cardiovascular Diseases; Cost-Benefit Analysis; Enalapril; Europe; Geography; Humans; Hypertension; Imidazoles; Male; Meta-Analysis as Topic; Middle Aged; Monte Carlo Method; Nitrendipine; Primary Prevention; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Stroke; Thiophenes

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Calcium Channel Blockers; Humans; Imidazoles; Nitrendipine; Randomized Controlled Trials as Topic; Stroke; Thiophenes

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Diseases; Follow-Up Studies; Humans; Imidazoles; Multicenter Studies as Topic; Nitrendipine; Prospective Studies; Randomized Controlled Trials as Topic; Stroke; Thiophenes; Treatment Outcome

Topics: Acrylates; Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Clinical Trials as Topic; Diuretics; Follow-Up Studies; Humans; Hypertension; Imidazoles; Meta-Analysis as Topic; Nitrendipine; Primary Prevention; Risk Factors; Stroke; Thiophenes; Time Factors

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Calcium Channel Blockers; Humans; Hypertension; Imidazoles; Nitrendipine; Randomized Controlled Trials as Topic; Stroke; Survival Rate; Thiophenes

Topics: Acrylates; Antihypertensive Agents; Coronary Disease; Enalapril; Humans; Hypertension; Imidazoles; Risk Factors; Stroke; Systole; Thiophenes; Treatment Outcome

The effects of the angiotensin type 1 (AT(1)) receptor antagonist, eprosartan, were studied in a model of severe, chronic hypertension. Treatment of male spontaneously hypertensive stroke prone rats (SHR-SP) fed a high-fat, high-salt diet with eprosartan (60 mg/kg/day i.p.) for 12 weeks resulted in a lowering of blood pressure (250 +/- 9 versus 284 +/- 8 mm Hg), renal expression of transforming growth factor-beta mRNA (1.5 +/- 0.2 versus 5.4 +/- 1.4) and the matrix components: plasminogen activator inhibitor-1 (5.2 +/- 1.4 versus 31.4 +/- 10.7), fibronectin (2.2 +/- 0.6 versus 8.2 +/- 2.2), collagen I-alpha 1 (5.6 +/- 2.0 versus 23.8 +/- 7.3), and collagen III (2.7 +/- 0.9 versus 7.6 +/- 2.1). Data were corrected for rpL32 mRNA expression and expressed relative to Wistar Kyoto (WKY) rats [=1.0]. Expression of fibronectin protein was also lowered by eprosartan (0.8 +/- 0.1 versus 1.9 +/- 0.5), relative to WKY rats. Eprosartan provided significant renoprotection to SHR-SP rats as measured by decreased proteinuria (22 +/- 2 versus 127 +/- 13 mg/day) and histological evidence of active renal damage (5 +/- 2 versus 195 +/- 6) and renal fibrosis (5.9 +/- 0.7 versus 16.4 +/- 1.9) in vehicle- versus eprosartan-treated rats, respectively. Our results demonstrated that AT(1) receptor blockade with eprosartan can reduce blood pressure and preserve renal structure and function in this model of severe, chronic hypertension. These effects were accompanied by a decreased renal expression of transforming growth factor-beta1, plasminogen activator inhibitor-1, and several other extracellular matrix proteins compared with vehicle-treated SHR-SP.

Topics: Acrylates; Angiotensin Receptor Antagonists; Animals; Blood Pressure; Blotting, Western; Body Weight; Dietary Fats; Disease Progression; Extracellular Matrix; Fibrinolysin; Gene Expression Regulation; Heart Rate; Hypertension; Imidazoles; Kidney Diseases; Male; Organ Size; Plasminogen Activator Inhibitor 1; Rats; Rats, Inbred SHR; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Serine Proteinase Inhibitors; Sodium Chloride, Dietary; Stroke; Thiophenes; Thrombosis

Eprosartan is a selective angiotensin II type I receptor antagonist approved for the treatment of hypertension. In the present studies, eprosartan's ability to provide end-organ protection was evaluated in a model of cardiomyopathy and renal failure in stroke-prone rats (SP).. SP were fed a high fat (24.5% in food) and high salt (1% in water) diet (SFD). Eprosartan (60 mg/kg/day) or vehicle (saline control) (n = 25/group) was administered by intraperitoneally-implanted minipumps to these SP on the SFD for 12 weeks. Normal diet fed SP and WKY rats (n = 25/group) were also included for comparison (i.e. served as normal controls). Mortality, hemodynamics, and both renal and cardiac function and histopathology were monitored in all treatment groups.. Eprosartan decreased the severely elevated arterial pressure (-12%; P < 0.05) produced by SFD but did not affect heart rate. Vehicle-treated SP-SFD control rats exhibited significant weight loss (-13%; P < 0.05) and marked mortality (50% by week 6 and 95% by week 9; P < 0.01). Eprosartan-treated SP-SFD rats maintained normal weight, and exhibited zero mortality at week 12 and beyond. Eprosartan prevented the increased urinary protein excretion (P < 0.05) that was observed in vehicle-treated SP-SFD rats. Echocardiographic (i.e. 2-D guided M-mode) evaluation indicated that SP-SFD vehicle control rats exhibited increased septal (+22.2%) and posterior left ventricular wall (+30.0%) thickness, and decreased left ventricular chamber diameter (-15.9%), chamber volume (-32.7%), stroke volume (-48.7%) and ejection fraction (-22.3%), and a remarkable decrease in cardiac output (-59.3%) compared to controls (all P < 0.05). These same parameters in eprosartan-treated SP-SFD rats were normal and differed markedly and consistently from vehicle-treated SP-SFD rats (i.e. treatment prevented pathology; all P < 0.05). Cardiac-gated MRI data confirmed the ability of eprosartan to prevent cardiac pathology/remodeling (P < 0.05). Histopathological analysis of hearts and kidneys indicated that eprosartan treatment significantly reduced end-organ damage (P < 0.01) and provided corroborative evidence that eprosartan reduced remodeling of these organs. Vehicle-treated SP-SFD rats exhibited a 40% increase in the plasma level of pro-atrial natiuretic factor that was reduced to normal by eprosartan (P < 0.05).. These data demonstrate that eprosartan, at a clinically relevant dose, provides significant end-organ protection in the severely hypertensive stroke-prone rat. It preserves cardiac and renal structural integrity, reduces cardiac hypertrophy and indices of heart failure, maintains normal function of the heart and kidneys, and eliminates premature mortality due to hypertension-induced end-organ failure.

Topics: Acrylates; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Cardiomegaly; Heart Rate; Hypertension; Imidazoles; Kidney; Magnetic Resonance Imaging; Male; Myocardium; Natriuresis; Organ Size; Peptide Fragments; Protein Precursors; Proteinuria; Rats; Rats, Inbred SHR; Stroke; Survival Rate; Thiophenes; Ventricular Remodeling

Topics: Acrylates; Animals; Antihypertensive Agents; Humans; Hypertension; Imidazoles; Randomized Controlled Trials as Topic; Rats; Stroke; Thiophenes