eprosartan and Hypertension

The benefits of reducing blood pressure (BP) have been well established, but uncertainty remains about the comparative effects of different BP-lowering regimens. We aimed to estimate the efficacy and the tolerability of eprosartan compared with other agents as monotherapy.. PubMed, EMBASE, and Cochrane Library were searched for relevant studies. A meta-analysis of randomized controlled trials (RCTs) meeting the criteria was performed using Review Manager and Stata/SE.. Twenty-two articles were ultimately included out of 78 studies, involving 6,460 patients. Eprosartan had a greater systolic blood pressure (SBP) reduction than placebo [weighted mean difference (WMD): 6.55, 95% confidence interval (CI) 4.86-8.25] and losartan (WMD: 2.24, 95% CI 0.08-4.40) and a greater diastolic blood pressure (DBP) reduction than placebo (WMD 3.95, 95% CI 2.77-5.13). Therapeutic response rate of BP favored eprosartan [risk ratio (RR) 1.13, 95% CI 1.03-1.24] compared with enalapril. There were no statistical differences in SBP or DBP reductions comparing eprosartan with enalapril or telmisartan. Original RCTs included comparing eprosartan with valsartan and nitrendipine reported no differences in BP-lowering efficacy.. Eprosartan monotherapy is equivalent to many first-line antihypertensive agents and is effective for the treatment of essential hypertension, especially for isolated systolic hypertension. The favorable efficacy and tolerability make eprosartan worthwhile to be taken into consideration by physicians.

Topics: Acrylates; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Randomized Controlled Trials as Topic; Thiophenes

Eprosartan is an angiotensin II receptor antagonist (angiotensin II receptor blocker [ARB]) used in the treatment of hypertension. In large, randomized trials, eprosartan (with or without hydrochlorothiazide [HCTZ]) demonstrated superior antihypertensive efficacy to that of placebo and, when administered at comparable dosage regimens, had similar blood pressure-lowering effects to enalapril. Eprosartan was generally well tolerated in clinical trials and had a lower incidence of persistent dry cough than enalapril. Eprosartan has a neutral effect on metabolic parameters, such as serum lipid levels and glucose homeostasis, and a low propensity for pharmacokinetic drug interactions. The use of eprosartan or other ARBs in combination with HCTZ tends to reverse the potassium loss associated with thiazide diuretics. Independent of its antihypertensive effects, eprosartan was associated with improved clinical outcomes (primary composite endpoint of all causes of mortality and all cardiovascular and cerebrovascular events, including all recurrent events) compared with nitrendipine in a randomized, secondary prevention trial in hypertensive patients with previous cerebrovascular events (MOSES trial). Eprosartan also reduced blood pressure and was associated with a modest improvement in cognitive function in a large observational study in patients > or =50 years of age with newly diagnosed hypertension (OSCAR study). In both of these trials, additional antihypertensive therapy, such as HCTZ, was permitted. Therefore, eprosartan is a useful treatment option in the management of a broad range of patients with hypertension, and its use with HCTZ provides a rational combination regimen.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Clinical Trials as Topic; Cough; Enalapril; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Incidence; Nitrendipine; Randomized Controlled Trials as Topic; Receptors, Angiotensin; Recurrence; Risk Factors; Sodium Chloride Symporter Inhibitors; Thiophenes; Treatment Outcome

Rationale. The goal of antihypertensive treatment is to reduce risk of cardiovascular morbidity and mortality. Apart from blood pressure lowering per se, also reducing the activities of the renin-angiotensin system and sympathetic nervous system appears to be important. Angiotensin II receptor blocker drugs (ARBs) have provided a useful class of anti-hypertensive drugs. Eprosartan is a relatively new ARB which is chemically distinct (non-biphenyl, non-tetrazole) from all other ARBs (biphenyl tetrazoles). An analysis has been made on available experimental and clinical data on eprosartan which not only is an effective and well tolerated antihypertensive agent, but also lowers the activities of the renin-angiotensin system and sympathetic nervous system. Experimental and pharmacokinetic studies on eprosartan have shown differences with the other ARBs. The distinct properties of this non-biphenyl, non-tetrazole ARB might be relevant in the effort to reduce cardiovascular risk, also beyond its blood pressure lowering capacity.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Humans; Hypertension; Imidazoles; Kidney Diseases; Renin-Angiotensin System; Sympathetic Nervous System; Thiophenes

The renin-angiotensin-aldosterone-system (RAAS) is an important regulator of blood pressure and fluid-electrolyte homeostasis. RAAS has been implicated in pathogenesis of hypertension, congestive heart failure, and chronic renal failure. Aliskiren is the first non-peptide orally active renin inhibitor approved by FDA. Angiotensin Converting Enzyme (ACE) Inhibitors are associated with frequent side effects such as cough and angio-oedema. Recently, the role of ACE2 and neutral endopeptidase (NEP) in the formation of an important active metabolite/mediator of RAAS, ang 1-7, has initiated attempts towards development of ACE2 inhibitors and combined ACE/NEP inhibitors. Furukawa and colleagues developed a series of low molecular weight nonpeptide imidazole analogues that possess weak but selective, competitive AT1 receptor blocking property. Till date, many compounds have exhibited promising AT1 blocking activity which cause a more complete RAAS blockade than ACE inhibitors. Many have reached the market for alternative treatment of hypertension, heart failure and diabetic nephropathy in ACE inhibitor intolerant patients and still more are waiting in the queue. But, the hallmark of this area of drug research is marked by a progress in understanding molecular interaction of these blockers at the AT1 receptor and unraveling the enigmatic influence of AT2 receptors on growth/anti-growth, differentiation and the regeneration of neuronal tissue. Different modeling strategies are underway to develop tailor made molecules with the best of properties like Dual Action (Angiotensin And Endothelin) Receptor Antagonists (DARA), ACE/NEP inhibitors, triple inhibitors, AT2 agonists, AT1/TxA2 antagonists, balanced AT1/AT2 antagonists, and nonpeptide renin inhibitors. This abstract gives an overview of these various angiotensin receptor antagonists.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Animals; Endothelin Receptor Antagonists; Humans; Hypertension; Imidazoles; Losartan; Protease Inhibitors; Receptors, Thromboxane A2, Prostaglandin H2; Renin; Renin-Angiotensin System; Thiophenes

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

The angiotensin II receptor antagonist eprosartan is approved for the treatment of essential hypertension and may be administered using a convenient once-daily regimen. The drug is a well tolerated and effective antihypertensive agent with benefit in the secondary prevention of cerebrovascular events, independent of blood pressure (BP)-lowering effects. Eprosartan has a low potential for serious adverse events and has not been associated with clinically significant drug interactions, establishing it as a promising agent for combination antihypertensive strategies. Unlike ACE inhibitors such as enalapril, eprosartan does not have a tendency to cause persistent nonproductive cough. Accordingly, eprosartan represents a useful therapeutic option in the management of patients with hypertension, including those who have had a stroke and those with co-morbid type 2 diabetes mellitus.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Clinical Trials as Topic; Humans; Hypertension; Imidazoles; Thiophenes

Candesartan is a novel high-affinity type 1 AT(1)-receptor blocker characterized by prolonged binding to and slow dissociation from the receptor. Pharmacokinetic properties of candesartan explain its pronounced and lengthy (24-36 hours) antihypertensive action which does not depend on patients sex, age and body mass. Long term use of candesartan has been associated with regression of left ventricular hypertrophy, renoprotective effect and lowered risk of stroke. Candesartan is well tolerated. All these features make the drug suitable for wide application in the management of hypertension. Preliminary results suggest that candesartan can be useful in the treatment of diabetic nephropathy.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Diabetic Nephropathies; Humans; Hypertension; Imidazoles; Irbesartan; Losartan; Tetrazoles; Thiophenes; Valine; Valsartan

Topics: Acrylates; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Growth Hormone; Humans; Hypertension; Imidazoles; Irbesartan; Losartan; Models, Molecular; Receptor, Angiotensin, Type 1; Tetrazoles; Thiophenes; Thromboxane A2

The ideal antihypertensive drug should be effective in reducing blood pressure, but have a low incidence of adverse effects. Angiotensin II receptor blockers, such as eprosartan, are as effective as ACE inhibitors in reducing blood pressure, but lack the main adverse effect of ACE inhibitors, namely cough. Eprosartan has been shown to be well tolerated with a placebo-like adverse-effect profile. When given as monotherapy it is effective in reducing blood pressure; however, some patients require additional blood pressure control, which may be provided by combination therapy. Indeed, the combination of eprosartan and the thiazide diuretic hydrochlorothiazide has been shown to be effective in further reducing blood pressure in patients not optimally responding to eprosartan monotherapy. This article reviews the safety and tolerability of eprosartan in combination with hydrochlorothiazide from 17 studies of 1899 patients with hypertension and normotensive volunteers. Of these studies, four were controlled with patients receiving a fixed-dose combination, six were long-term, open-label, and another four were controlled studies with hydrochlorothiazide being given to eprosartan non-responders. The other three studies included healthy subjects receiving the combination of eprosartan and hydrochlorothiazide. There was a high completion rate in all studies evaluated. Most of the patients receiving eprosartan 600mg in combination with hydrochlorothiazide 12.5mg daily completed the studies, which supports acceptance of this combination therapy by patients. The most frequently reported adverse events in these combination studies were headache, dizziness, myalgia, and upper respiratory tract infection in patients with hypertension. The majority of adverse events were mild to moderate in intensity, and were not considered to be related to study treatment. The adverse event that was more common in patients receiving combination therapy compared with those receiving monotherapy was dizziness. This adverse event may be due to hydrochlorothiazide as it has previously been observed in patients taking thiazide diuretics. In healthy volunteers, the most frequently reported adverse events were headache, dizziness, and upper respiratory tract infection. However, none of these adverse events were considered related to study medication. In summary, the combination of eprosartan/hydrochlorothiazide is well tolerated, both as short- and long-term therapy, with most adverse events o

Topics: Acrylates; Age Factors; Antihypertensive Agents; Drug Combinations; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Thiophenes

Angiotensin II receptor antagonists block angiotensin II type 1 (AT1) receptors and reduce the pressor effects of angiotensin in the vasculature. By this mechanism, they induce similar pharmacological effects to angiotensin-converting enzyme (ACE) inhibitors, resulting in a lowering of blood pressure (BP). However, AT1 antagonists differ from ACE inhibitors with respect to side effects, and induce less cough, which is related to bradykinin activation. Within the class of angiotensin II antagonists, eprosartan differs from other currently clinically available agents in terms of its chemical structure and its dual pharmacological mode of action. Eprosartan acts not only at vascular AT1 receptors but also at presynaptic AT1 receptors, causing inhibition of sympathetically stimulated noradrenaline release. Eprosartan is not metabolized by cytochrome P450 enzymes and therefore has a low potential for metabolic drug interactions, which may be of importance when treating the elderly and patients on multiple drugs. In clinical trials eprosartan has proven to be at least as effective as the ACE inhibitor enalapril in reducing BP, but with a significantly lower incidence of side effects. Eprosartan is safe, effective and well tolerated in long-term treatment, either as monotherapy or in combination with other antihypertensive drugs such as hydrochlorothiazide.

Topics: Acrylates; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Drug Interactions; Drug Therapy, Combination; Humans; Hypertension; Imidazoles; Receptor, Angiotensin, Type 1; Thiophenes

Topics: Acrylates; Adrenergic alpha-Antagonists; Age Factors; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzothiadiazines; Calcium Channel Blockers; Clinical Trials as Topic; Diuretics; Doxazosin; Female; Humans; Hypertension; Imidazoles; Losartan; Male; Perindopril; Risk Factors; Sex Factors; Sodium Chloride Symporter Inhibitors; Thiophenes

Angiotensin II type 1 receptor blockers (AT1RBs) share the effect of attenuating angiotensin II actions with angiotensin-converting enzyme inhibitors (ACEIs) but differ in other respects. Notably, the impact of unopposed angiotensin type 2 receptor stimulation and the absence of augmentation of bradykinin through inhibition of the kininase pathway may lead to differences between the effects of AT1RBs and ACEIs. ACEIs have been shown to improve endothelial dysfunction in many clinical settings.. To review current evidence regarding the effects of AT1RBs on endothelial dysfunction in patients.. MEDLINE and Current Contents searches, augmented by careful analyses of the bibliographies in the identified papers, were used to identify studies assessing the effects of chronic, oral use of AT1RBs on endothelial function and related inflammatory markers in patients. Animal studies and human studies using single doses or intravenous infusions were excluded.. Clinical studies are available pertaining to the elderly and patients with coronary artery disease, hypertension and diabetes. The effect on endothelial dysfunction induced by postprandial lipemia has also been assessed. In general, AT1RBs improve vasomotor endothelial dysfunction and some inflammatory markers, but a few studies comparing ACEIs directly with AT1RBs suggest that AT1RBs may be inferior. AT1RB activity on endothelial dysfunction in patients with type I diabetes has not been shown.. AT1RBs are an important addition to the therapy of endothelial dysfunction and vascular inflammation in patients. Further research is necessary to determine which AT1RBs and which dosing regimens are optimal.

Topics: Acrylates; Aged; Antihypertensive Agents; Benzimidazoles; Biomarkers; Biphenyl Compounds; Coronary Artery Disease; Data Interpretation, Statistical; Diabetes Mellitus; E-Selectin; Endothelium, Vascular; Humans; Hypertension; Imidazoles; Irbesartan; Losartan; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Tetrazoles; Thiophenes; Vasculitis

Hypertension means a basic public health problem in many countries in the world. The therapeutic attempts of the last years did not fulfill the hopes pinned on them, and most of the patients live with blood pressure above the goal value. This is why there is a need for new, more efficient antihypertensive drugs. On the 1st of July, 2001 irbesartan (Aprovel) was introduced in practice in Hungary. The drug belongs to the family of the angiotensin II receptor inhibitors. Several clinical studies were made with irbesartan in order to evaluate its efficiency, tolerability and safety. In other studies it was compared with other antihypertensive treatments and it was found that irbesartan decreases the systolic and diastolic blood pressure as effectively as other first line medicaments. The author summarizes the most important characteristics of irbesartan as well as the results of those clinical studies which show evidence that irbesartan deserves a special place among antihypertensive drugs.

Topics: Acrylates; Angiotensin Receptor Antagonists; Antihypertensive Agents; Atenolol; Benzimidazoles; Benzoates; Biological Availability; Biphenyl Compounds; Controlled Clinical Trials as Topic; Drug Administration Schedule; Enalapril; Half-Life; Humans; Hypertension; Imidazoles; Irbesartan; Losartan; Telmisartan; Tetrazoles; Thiophenes; Valine; Valsartan

Angiotensin receptor antagonists (ARB) are equally effective but better tolerated than all the other blood pressure lowering agents. The reason, why they are not subscribed as first line drugs for uncomplicated hypertension, is the higher price for these products. What the real difference in costs is, remains unclear because calculations are missing to what extent lesser controls of therapy would shift the balance in favour of the ARBs. For other indications than hypertension, but often associated with that condition, be it per se or as a consequence of it, the effects of the ARBs are studied in large trials these days. For some of them the benefit, which has been proven for ACE inhibitors, is not yet established for the ARBs, but evidence emerges that they are also useful in the treatment of cardiac failure, left ventricular hypertrophy and diabetic and other kinds of nephropathy. A large percentage of hypertensive patients can be treated effectively with ARBs without considerable side effects, thus increasing adherence and minimizing the necessity of safety controls.

Topics: Acrylates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Austria; Benzimidazoles; Benzoates; Biphenyl Compounds; Humans; Hypertension; Imidazoles; Losartan; Prodrugs; Telmisartan; Tetrazoles; Therapeutic Equivalency; Thiophenes; Valine; Valsartan

Improvements in the death rate from coronary heart disease and in the control of hypertension have leveled off in recent years, reversing a trend toward steady improvement that began in 1972. Of the roughly 20% of Americans who suffer from hypertension, only 29% achieve adequate control (<140/90 mm Hg) with treatment and nearly half receive no treatment at all. Poor adherence to therapy doubtless plays a key role in this failure. As a major cause of poor adherence, tolerability becomes an extremely important element in any discussion of effective antihypertensive treatment. Despite their efficacy in treating hypertension, diuretics, beta-blockers, and calcium channel blockers have all been associated with numerous side effects, including increased serum lipid levels, insulin resistance, and edema. With the introduction of the angiotensin converting enzyme (ACE) inhibitors, patients were able to achieve blood pressure goals with fewer side effects. These agents, however, cause an irritating cough in up to 19% of patients. A newer class of drugs, the angiotensin receptor blockers (ARB), have similar effects to the ACE inhibitors, but their highly selective nature produces even fewer side effects. Eprosartan is a structurally unique ARB. Like the other ARB, this promising new agent has a side effect profile similar to placebo, and its response rate rivals or exceeds that of enalapril. Although it remains to be seen whether the ARB can significantly reduce morbidity and mortality from cardiovascular disease, preliminary data from the Evaluation of Losartan in the Elderly (ELITE) trial appear to be promising.

Topics: Acrylates; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Drug Interactions; Humans; Hypertension; Imidazoles; Middle Aged; Patient Compliance; Receptors, Angiotensin; Thiophenes; United States

The treatment of hypertension has become increasingly refined during the past decade. Although a variety of antihypertensive medication classes exist, drugs that interrupt the renin-angiotensin axis have gained a favored position in the treatment of hypertension and its attendant end-organ complications. In this regard, two drug classes, angiotensin converting enzyme inhibitors and angiotensin receptor blockers, are most commonly used. Angiotensin receptor blockers have proven highly effective in the management of hypertension. This class is fairly heterogeneous with individual class members having somewhat distinctive pharmacologic properties. Eprosartan is a recent entry into this class. This compound compares favorably to others in this class relative to blood pressure reduction. In addition, preliminary studies indicate that this compound may uniquely interrupt the sympathetic nervous system and thereby preferentially reduce systolic blood pressure.

Topics: Acrylates; Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Humans; Hypertension; Imidazoles; Renin-Angiotensin System; Sympathetic Nervous System; Thiophenes; Treatment Outcome

When angiotensin-converting enzyme (ACE) inhibition first became available to block the renin system, few could have predicted the evolution that would occur in this field. The advent of angiotensin II receptor 1 (AT(1)) blockers has created new opportunities. These agents, including eprosartan, are extraordinarily well tolerated, not only when compared with antihypertensive agents but also in comparison with the ACE inhibitors, which are rather well tolerated. The AT(1) blocker class is growing rapidly, at least in part because many believe that these drugs will share with the ACE inhibitors the special ability to reduce morbidity and mortality. Does eprosartan have a special role within this class? Eprosartan differs structurally from the other AT(1) blockers in that it is not a biphenyl tetrazole. It differs functionally in vitro in being a pure competitive antagonist, as opposed to the nonequilibrium, insurmountable characteristics of the other blockers. This feature may prove to be useful for titration in the fragile patient. The reduction in catecholamine release induced by eprosartan that has been observed in animal models may account for some special examples of increased efficacy. One such example pertains to the difference in the dose-response relationship for the action of eprosartan on the renal blood supply in comparison with other AT(1) blockers. Eprosartan doses well below those required for control of blood pressure have a pronounced effect on the kidney. If research already under way supports these early suggestions, then eprosartan will be an important addition to our therapeutic armamentarium.

Topics: Acrylates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Heart Failure; Humans; Hypertension; Imidazoles; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin-Angiotensin System; Sympathetic Nervous System; Thiophenes; Treatment Outcome

Control of systolic blood pressure should be the primary goal of treatment as it is increasingly recognized as a major determinant of cardiovascular risk. Better control offers enormous potential benefits. Effective treatment is desirable but difficult to achieve. All antagonists, particularly eprosartan, are likely to have an increasingly important role in management strategies.

Topics: Acrylates; Angiotensin II; Antihypertensive Agents; Blood Pressure; Delivery of Health Care; Humans; Hypertension; Imidazoles; Renin-Angiotensin System; Systole; Thiophenes

Topics: Acrylates; Aldosterone; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Biphenyl Compounds; Drug Therapy, Combination; Heart; Humans; Hypertension; Imidazoles; Irbesartan; Kidney; Losartan; Renin-Angiotensin System; Telmisartan; Tetrazoles; Thiophenes

Eprosartan is a potent and selective angiotensin II subtype 1 receptor antagonist. Results of large (n > 100) randomised double-blind studies in patients with mild, moderate or severe hypertension demonstrated that the antihypertensive efficacy of eprosartan (usually 400 to 800 mg/day as a single daily dose or in 2 divided doses) is significantly greater than that of placebo and at least as good as that of enalapril. In placebo-controlled trials, eprosartan achieved mean reductions from baseline in trough sitting systolic blood pressure of 6.3 to 15 mm Hg and in diastolic blood pressure of 4.1 to 9.7 mm Hg. Response rates associated with once daily administration of eprosartan 400 to 800 mg were approximately double those with placebo. Overall, eprosartan was well tolerated with a similar tolerability profile to that of placebo. In comparative trials, in which the incidence of persistent dry cough was evaluated as the primary end-point, enalapril was several-fold more likely to induce this adverse event than eprosartan (the difference being statistically significant regardless of study population and definition of cough). In conclusion, the angiotensin II receptor antagonist eprosartan is a well tolerated and effective antihypertensive agent that is administered once or twice daily without regard to meals. Eprosartan has a low potential for serious adverse events, and the drug has not been associated with clinically significant drug interactions. Unlike ACE inhibitors such as enalapril, eprosartan does not have a high propensity to cause persistent nonproductive cough. Thus, eprosartan represents a useful therapeutic option in the management of patients with hypertension.

Topics: Acrylates; Antihypertensive Agents; Humans; Hypertension; Imidazoles; Thiophenes

Pressure overload of the heart is associated with a perturbed gene expression of the cardiomyocyte leading to an impaired pump function. The ensuing neuro-endocrine activation results in disordered influences of angiotensin II and catecholamines on gene expression. To assess whether angiotensin II type 1 receptor inhibition can also counteract a raised sympathetic nervous system activity, spontaneously hypertensive rats fed a hypercaloric diet were treated with eprosartan (daily 90 mg/kg body wt) and cardiovascular parameters were monitored with implanted radiotelemetry pressure transducers. Both, blood pressure and heart rate were increased (p < 0.05) by the hypercaloric diet. Although eprosartan reduced (p < 0.05) the raised systolic and diastolic blood pressure, the diet-induced rise in heart rate was blunted only partially. In addition to drugs interfering with the enhanced catecholamine influence, compounds should be considered that selectively affect cardiomyocyte gene expression via 'metabolic' signals.

Topics: Acrylates; Amino Acid Sequence; Animals; Antihypertensive Agents; Calcium-Transporting ATPases; Catecholamines; Gene Expression Regulation; Heart Failure; Humans; Hypertension; Imidazoles; Molecular Sequence Data; Myocardium; Myosin Heavy Chains; Rats; Rats, Inbred SHR; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Sequence Alignment; Sequence Homology, Amino Acid; Thiophenes

Topics: Acrylates; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Humans; Hypertension; Imidazoles; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin-Angiotensin System; Sympathetic Nervous System; Thiophenes

Angiotensin II (Ang II) has diverse physiological actions leading, for example, to increases in extracellular volume, peripheral vascular resistance and blood pressure, and has also been implicated in the regulation of cell growth and differentiation. Molecular cloning and pharmacological studies have defined two major classes of Ang II receptors, designated as AT1 and AT2. Most effects of Ang II are mediated by AT1 receptors. Much less is known about the physiological role of AT2 receptors. Recent evidence suggests involvement of AT2 receptors in development, cell differentiation, apoptosis and regeneration in various tissues. AT1 and AT2 receptors have been shown to exert counteracting effects on cellular growth and differentiation, vascular tone and the release of arginine vasopressin (AVP). In each condition the AT2 receptor appears to down-modulate actions mediated by the AT1 receptor, resulting in decreased cellular proliferation, decreased levels of serum AVP levels or decreased vasoconstrictor responses. In addition, in neuronal cell lines, the AT2 receptor reportedly exerts antiproliferative effects and promotes neurite outgrowth, an effect accompanied by significant changes in the gene expression pattern of growth- and differentiation-related genes.

Topics: Acrylates; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Humans; Hypertension; Imidazoles; Irbesartan; Losartan; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin; Tetrazoles; Thiophenes

After oral administration of eprosartan to healthy volunteers, bioavailability is approximately 13%, with peak plasma concentrations occurring 1-2 hours after an oral dose in the fasted state. Food slows the rate of absorption and changes the overall extent by less than 25%, which is unlikely to be of clinical consequence. Plasma concentrations increase in a slightly less than dose-proportional manner from 100-800 mg. There is no evidence of significant accumulation of eprosartan with long-term therapy. The drug's terminal elimination half-life is typically 5-9 hours after oral administration. The agent is highly protein bound (approximately 98%), with low plasma clearance (approximately 130 ml/minute) and small volume of distribution (approximately 13 L). It is primarily unmetabolized by the liver, with less than 2% of an oral dose recovered in the urine as a glucuronide. Biliary (primary) and renal excretion contribute to its elimination. No dosage adjustment is required in patients with mild to moderate renal impairment. Although an increase in systemic exposure to eprosartan was observed in the elderly, in patients with hepatic impairment, and in those with severe renal disease, this finding is unlikely to be of clinical consequence, based on the drug's excellent safety and tolerability profile (doses up to 1200 mg) in phase III clinical trials in hypertensive patients. Eprosartan can be safely administered to these special populations without an initial dosage adjustment, with subsequent dosing individualized based on tolerability and response.

Topics: Absorption; Acrylates; Age Factors; Antihypertensive Agents; Biological Availability; Clinical Trials, Phase III as Topic; Humans; Hypertension; Imidazoles; Sex Factors; Thiophenes

The safety and tolerability of eprosartan were extensively assessed in 17 phase IIb-III studies that included 2709 patients with hypertension. The frequency of adverse events observed with eprosartan was similar to that seen with placebo. Neither the number nor the severity of these effects increased with prolonged therapy, and their frequency was not affected by increased eprosartan dosage or dosing frequency. The drug is equally well tolerated by women and men, by younger (< 65 yrs) and older (> or = 65 yrs) individuals, and by persons of all races. There are no known drug interactions, and eprosartan is well tolerated when given in combination with other frequently prescribed antihypertensive agents, without an increase in adverse events beyond those expected of baseline antihypertensive therapy.

Topics: Acrylates; Antihypertensive Agents; Clinical Trials as Topic; Drug Tolerance; Humans; Hypertension; Imidazoles; Thiophenes

Systolic hypertension is a major risk factor for cardiovascular disease. The determinants of systolic blood pressure are peripheral resistance and arterial compliance. Arterial vasoconstriction, vascular growth and fluid retention, induced by the renin-angiotensin system directly or indirectly by enhancing sympathetic nervous system activity, are important factors in increasing peripheral resistance, decreasing arterial compliance and, consequently, elevating systolic blood pressure. Selective blockade of the angiotensin II type 1 (AT1) receptor represents a novel mechanism for interrupting the renin-angiotensin system. This provides the additional benefit of blocking angiotensin II generated by non-angiotensin-converting-enzyme pathways without altering either bradykinin metabolism or the potential beneficial effects of AT2 receptor stimulation. Eprosartan is a potent (1.4 nmol/l) AT1 receptor antagonist that inhibits angiotensin-II-induced vascular contraction in a competitive manner. Eprosartan is effective in reducing disease progression in animal models of hypertension, heart failure, renal disease and stroke. Furthermore, eprosartan causes a large increase in arterial compliance in hypertensive rats fed high-salt and high-fat diets. Eprosartan also possesses sympathoinhibitory activity as demonstrated by an inhibition of the pressor responses induced by activation of sympathetic outflow through spinal cord stimulation in pithed rats. In contrast, other angiotensin II receptor antagonists, such as losartan, used at equivalent angiotensin II blocking activity, do not appear to alter sympathetic nervous system activity. Angiotensin II receptor antagonists, such as eprosartan, that have the ability to block both the direct effects of angiotensin II and the indirect effects mediated by enhanced sympathetic neurotransmission, may represent an important advance in the treatment of elevated systolic blood pressure.

Topics: Acrylates; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Imidazoles; Renin-Angiotensin System; Sympathetic Nervous System; Systole; Thiophenes; Treatment Outcome; Vascular Resistance

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1) receptor antagonists have received increased therapeutic recognition in the treatment of hypertension. Although the overall effects of the ACE inhibitors and AT1 receptor antagonists may seem superficially similar, there are important differences between the two classes in terms of neurohumoral activation, concomitant bradykinin potentiation, and inhibition of angiotensin II, derived not only from the classical ACE pathway, but also from alternative pathways. The AT1 receptor antagonist eprosartan has been shown to lower blood pressure effectively in hypertensive patients. When taken in the recommended dose range, 600-800 mg once daily, eprosartan is effective in patients with all grades of hypertension, regardless of age, sex or race. In several clinical studies, the blood-pressure-lowering effect of eprosartan has been shown to be at least as great as that of the ACE inhibitor enalapril. With respect to tolerability, eprosartan is superior to ACE inhibitor therapy and comparable to placebo. The pharmacological and therapeutic profiles of the expanding array of AT1 receptor antagonists differ in a number of respects. Most of these agents are biphenyl tetrazole, non-competitive antagonists, and some have active metabolites. Eprosartan differs from other AT1 receptor antagonists in that it is a non-biphenyl, non-tetrazole competitive antagonist without active metabolites. Several large-scale, ongoing clinical research programmes (e.g. LIFE, SCOPE and VALUE) are expected to provide information on the extent to which AT1 receptor antagonists, in comparison with other therapeutic regimens, reduce cardiovascular morbidity and mortality in different groups of hypertensive subjects. Meanwhile, current evidence suggests that the AT1 receptor antagonists provide a new approach to the management of hypertension and that they merit a fuller assessment in other cardiovascular diseases.

Topics: Acrylates; Angiotensin Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Enalapril; Humans; Hypertension; Imidazoles; Survival Rate; Thiophenes; Treatment Outcome

Angiotensin-converting enzyme inhibitors have been used extensively in the management of hypertension and related cardiovascular conditions. However, this treatment approach is limited by lack of specificity and continued production of angiotensin II by other routes. Antagonism of the angiotensin II receptor offers the possibility of improved control of hypertension by providing a more complete blockade of the renin-angiotensin system than angiotensin-converting enzyme inhibition without bradykinin-related effects. Eprosartan is the only nonbiphenyl, nontetrazole competitive angiotensin II receptor antagonist clinically available and is highly selective for the AT1 receptor subtype. In clinical trials, eprosartan has been shown to lower blood pressure effectively in a once-daily regimen in hypertensive patients. In the recommended dose range of 600 to 1200 mg once daily, eprosartan is effective in patients with all grades of hypertension irrespective of age, sex, or race. Furthermore, the tolerability profile of eprosartan is comparable to that of placebo, and there are no known clinically relevant drug-drug interactions. A number of large-scale clinical studies are currently underway or planned to determine which of the increasing number of AT1 receptor antagonists may reduce cardiovascular morbidity and mortality rates in different groups of hypertensive patients. Meanwhile, current evidence suggests that the AT1 receptor antagonists represent a significant new approach to cardiovascular therapy and merit a fuller assessment in hypertension and other cardiovascular diseases.

Topics: Acrylates; Angiotensin II; Antihypertensive Agents; Cardiovascular Diseases; Drug Interactions; Humans; Hypertension; Imidazoles; Thiophenes

Selective blockade of the angiotensin II AT1 receptor represents a novel mechanism for interrupting the renin-angiotensin system without altering the potential benefits of AT2 receptor stimulation. This selective inhibition produces none of the disadvantages associated with reduced bradykinin metabolism and angiotensin II generated by non-angiotensin-converting enzyme pathways. Eprosartan is a potent (1.4 nmol/L) AT1 receptor antagonist that competitively blocks angiotensin II-induced vascular contraction. In various animal models of disease, including hypertension and stroke, eprosartan is effective in reducing disease progression. Eprosartan also has sympathoinhibitory activity, as demonstrated by an inhibition of the pressor responses induced by activation of sympathetic outflow through spinal cord stimulation in pithed rats. In contrast, some of the other angiotensin II receptor antagonists, such as losartan, at equivalent angiotensin II blocking doses, have no effect on sympathetic nervous system activity. Because eprosartan can inhibit both the direct effects of angiotensin II as well as the indirect effects that are mediated by enhanced sympathetic neurotransmission, this may represent an important advance in the treatment of elevated systolic blood pressure.

Topics: Acrylates; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Blood Pressure; Cerebrovascular Disorders; Disease Models, Animal; Humans; Hypertension; Imidazoles; Rats; Receptors, Angiotensin; Renin-Angiotensin System; Sympathetic Nervous System; Thiophenes

Angiotensin II (ANG II) is the primary mediator of the renin-angiotensin system, which has an important functional role in cardiovascular homeostasis. The angiotensin receptor and its functional correlates have been redefined by the cloning of angiotensin receptors and the discovery and widespread study of specific nonpeptide ANG II-receptor antagonists losartan (AT1 selective) and PD123177 (AT2 selective). With these antagonists, it has been possible to extend the concept of ANG II-receptor heterogeneity to virtually every tissue and species. The losartan-sensitive sites have been shown to mediate all of the major ANG II-induced biologic effects, including vasoconstriction, aldosterone and catecholamine release, and central, ANG II-induced drinking behavior. The function of the AT2 site is not fully understood, but it may be involved in neuronal ion channel modulation and in fibroblast collagen metabolism. The presence of AT2 sites in fetal tissues and in discrete locations in the brain has encouraged continued research. Losartan, which represents the first of a new class of therapeutic agents, is currently undergoing clinical trials. A growing number of other AT1-selective ANG II-receptor antagonists are under development, including L-158,809, SKF 108566, and GR117285. Rat AT1-receptor subtypes have been cloned and sequenced (AT1A and AT1B). Human ANG II receptors have also been cloned and shown to have high affinity for losartan. A number of atypical angiotensin-binding sites have been identified from mycoplasma, amphibians, and mouse neuroblastoma, which are not sensitive to either losartan or PD123177.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acrylates; Angiotensin Receptor Antagonists; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Humans; Hypertension; Imidazoles; Losartan; Pyridines; Receptors, Angiotensin; Renin-Angiotensin System; Tetrazoles; Thiophenes

Excessive intake of fructose increases serum uric acid concentration. Hyperuricemia induces a negative effect on atherosclerosis and inflammation. Hyperuricemia is common in patients with arterial hypertension. Several antihypertensive drugs including diuretics increase serum uric acid concentration. In contrast, the angiotensin II receptor antagonist (ARB) losartan was found to lower serum uric acid though it may increase renal excretion while other ARBs showed mostly a neutral effect. In this study, effects of two AT1 receptor antagonists losartan and eprosartan on serum uric acid changes induced by oral fructose load were directly compared.. The randomized, crossover, head-to-head comparative study comprised 16 ambulatory patients (mean age 64.5 ± 9.8 years). The patients fulfilled AHA/NHLBI 2005 criteria of metabolic syndrome. A daily single morning dose of each study drug (50 mg of losartan or 600 mg of eprosartan) was given during two 3-month periods in a random order separated by 2-week washout time. The oral fructose tolerance test (OFTT) was performed at baseline and after each two 3-onth treatment periods. Before and during OFTT, urine excretion of uric acid and creatinine was assessed in the first morning portion of urine. Blood samples for the measurement of serum uric acid and lipids were taken at baseline and 30, 60, and 120 minutes after oral intake of 75 g of fructose.. After 3-month treatment with eprosartan and losartan, both systolic and diastolic blood pressure decreased significantly and to a similar extent. After the treatment, serum uric acid and its baseline and postfructose urine excretion were unchanged. No significant changes of plasma lipids before and after OFTT were observed throughout the study.. The study showed that in patients with hypertension and metabolic syndrome, both losartan and eprosartan have a neutral effect on fasting and postfructose load serum uric acid concentration and its urinary excretion. This trial is registered with NCT04954560.

Topics: Acrylates; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Fructose; Humans; Hypertension; Imidazoles; Losartan; Metabolic Syndrome; Middle Aged; Thiophenes; Uric Acid

It is well recognized that many antihypertensive drugs exhibit large interindividual variability in effect and that this wide range of patient response to antihypertensive drugs is a major problem in achieving blood pressure (BP) control. Variability in both drug concentration and drug effect may cause the heterogeneity in antihypertensive drug response. However, for most antihypertensive drugs, no clear relationship between drug concentration and its effect on BP has been reported. This study aimed to describe the relationship between eprosartan exposure and its effect on the systolic blood pressure (SBP) using population pharmacokinetic-pharmacodynamic modeling. Interindividual variability in pharmacokinetics and pharmacodynamics was quantified and the influence of covariates on this relationship was evaluated.. Eprosartan plasma concentrations and SBP measurements were determined in 86 mildly hypertensive patients from the ROTATE study aged 48.1 ± 7.6 years with different ethnic backgrounds (33 White Dutch, 41 Creole Surinamese, 12 Hindustani Surinamese). In 12 of these patients, pharmacokinetics were densely sampled and 24-h ambulatory BP measurements were obtained. Data were analyzed using nonlinear mixed effects modeling.. Eprosartan concentration-time profiles were adequately described with a two-compartment pharmacokinetic model with zero-order absorption. A log-linear relationship was used to describe the relationship between concentration and the decrease in SBP. A hypothetical effect compartment was used to describe hysteresis in the drug effect. Approximately 80 % of the maximum decrease in SBP was observed after 24 days. Interindividual variability in drug response was 65 % and decreased to 14 % when ethnicity was added as covariate. Creole Surinamese exhibited no drug response in contrast to White Dutch and Hindustani Surinamese [-2.6 mm Hg per (ng/ml)].. The developed pharmacokinetic-pharmacodynamic model allows the quantification and explanation of variability in SBP between individuals with ethnicity as a useful determinant of responsiveness to eprosartan.

Topics: Acrylates; Adult; Antihypertensive Agents; Black People; Blood Pressure; Cross-Over Studies; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Models, Biological; Thiophenes; White People

Studies have indicated a relationship between hypertension and cognitive function. The possible effect of antihypertensive therapy on cognitive disorders is therefore a matter of interest.. The Observational Study on Cognitive function And SBP Reduction (OSCAR) was an open-label, multinational trial designed to evaluate the impact of eprosartan-based antihypertensive therapy on cognitive function in patients with essential hypertension. Eprosartan 600 mg/day for 6 months (with provision for additional medication as needed) was initiated in hypertensive subjects aged ≥ 50 years. A total of 853 patients in an intention-to-treat cohort from seven countries of the Middle East was identified for subgroup analysis.. Arterial blood pressure was reduced significantly (P < 0.001) during the study: At the end of 6 months of eprosartan-based therapy, the mean (±SD) reduction from baseline was 32.1 ± 14.3/14.6.3 ± 8.6 mmHg (P < 0.001). Mean pulse pressure was reduced by 18.3 ± 13.1 mmHg (P < 0.0001 vs baseline). Blood pressure was normalized (systolic <140 mmHg and diastolic <90 mmHg) in 68.2% of patients. The overall mean Mini-Mental State Examination (MMSE) score after 6 months of eprosartan-based therapy was one-point higher than at baseline (P < 0.001). MMSE score on completion of 6 months' follow-up was either unchanged or increased from baseline in 793 (93%) individuals and decreased in 60 (7%). Factors associated with stability of or improvement in cognitive function included MMSE score at baseline, diastolic blood pressure (DBP) at baseline, and treatment-induced change in DBP.. Results from the Middle East subgroup of OSCAR are supportive of the hypothesis that antihypertensive therapy based on angiotensin-receptor blocker therapy with eprosartan may be associated with preservation or improvement of cognitive function.

Topics: Acrylates; Aged; Analysis of Variance; Angiotensin II Type 2 Receptor Blockers; Antihypertensive Agents; Arabs; Blood Pressure; Chi-Square Distribution; Cognition; Female; Humans; Hypertension; Imidazoles; Logistic Models; Male; Middle Aged; Middle East; Psychiatric Status Rating Scales; Thiophenes; Time Factors; Treatment Outcome

To investigate the relationship between advanced glycation end-products (AGEs) and diastolic function and the response to blood pressure treatment in patients with hypertension and diastolic dysfunction.. Data were analysed from 97 patients (aged 65 +/- 10 years, 36% male) who were randomly assigned to 6 months open-label treatment with either eprosartan on top of other anti-hypertensive drugs (n = 47) or other anti-hypertensive drugs alone (n = 50). Tissue AGE accumulation was measured using a validated skin-autofluorescence (skin-AF) reader (n = 26). Plasma N(epsilon)-(carboxymethyl)lysine (CML), N(epsilon)-(carboxyethyl)lysine (CEL), and pentosidine were measured by LC-MS/MS and HPLC. Diastolic function was assessed using echocardiography. Blood pressure was reduced from 157/91 to 145/84 mmHg (P < 0.001) in the eprosartan group and from 158/91 to 141/83 mmHg (P < 0.001) in the control group. No effect of eprosartan was found on AGE levels. In patients with baseline skin-AF < median, E/A ratio (P = 0.04) and the mean peak early-diastolic filling velocity (E') improved (P = 0.001). In contrast, in patients with skin-AF levels > median, E/A ratio (P = 0.84) and mean E' (P = 0.32) remained unchanged.. Although eprosartan did not decrease levels of AGEs, patients with lower skin-AF at baseline showed a larger improvement in diastolic function in response to either anti-hypertensive treatment compared with patients with higher skin-AF.

Topics: Acrylates; Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Diastole; Female; Glycation End Products, Advanced; Humans; Hypertension; Imidazoles; Linear Models; Lysine; Male; Middle Aged; Multivariate Analysis; Netherlands; Skin; Statistics as Topic; Statistics, Nonparametric; Stroke Volume; Thiophenes; Ventricular Function, Left

To compare the effects of an angiotensin receptor blocker(ARB)-based regimen versus a non-ARB based regimen on diastolic function and neurohormones in patients with hypertension and diastolic dysfunction.. 97 patients with a systolic blood pressure (SBP) > or =140 mmHg, a left ventricular ejection fraction >0.50, and echocardiographic evidence of diastolic dysfunction were randomly assignment to open-label treatment with eprosartan (with other anti-hypertensives; n = 47) or other anti-hypertensives alone (n = 50). Echocardiography, including tissue Doppler imaging (TDI), and neurohormones were done at baseline and after 6 months.. Mean age was 65 (+/-10) years and 64% was female. During 6 months of treatment, SBP decreased from 157 +/- 16 to 145 +/- 18 mmHg in the eprosartan group and from 158 +/- 17 to 141 +/- 18 mmHg in the control group (both p < 0.001; p = ns between groups). Diastolic function was unaffected in both groups and there was no correlation between changes in SBP and changes in mean TDI (r = -0.06; p = 0.58). Aldosterone levels decreased in the eprosartan group, but other neurohormones remained largely unchanged. Change in SBP was however related to the change in NT-proBNP (r = 0.26; p = 0.019).. Lowering blood pressure, either with eprosartan or other anti-hypertensives in hypertensive patients with diastolic dysfunction did not change diastolic function after 6 months of treatment, but was associated with a decrease of NT-proBNP.

Topics: Acrylates; Aged; Aldosterone; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Diastole; Echocardiography; Female; Heart; Humans; Hypertension; Imidazoles; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Peptide Fragments; Peptidyl-Dipeptidase A; Stroke Volume; Thiophenes; Treatment Outcome; Ventricular Dysfunction; Ventricular Function; Ventricular Function, Left

Systolic hypertension is very common in the elderly and is strongly associated with the risk of cardiovascular and cerebrovascular events. The control of systolic hypertension is difficult and most patients require combination antihypertensive therapy. Few data are available regarding the efficacy of angiotensin II receptor antagonists on systolic hypertension of the elderly. The aim of this double-blind, double-dummy, randomized, parallel-group, multicenter study was to assess the efficacy of eprosartan 600 mg in combination with hydrochlorothiazide (HCTZ) 12.5 mg in comparison with losartan 50 mg in combination with HCTZ 12.5 mg, in reducing blood pressure in elderly patients with grade 2 systolic hypertension who did not optimally respond to eprosartan or losartan monotherapy.. After a 3-week placebo wash-out, 155 patients with an Office trough sitting systolic blood pressure (Office sitSBP) >or=160 mmHg and <180 mmHg were randomized to eprosartan 600 mg (n=78) or losartan 50 mg (n=77) once daily for 6 weeks. In patients not optimally responding to monotherapy (Office sitSBP>or=130 mmHg) 12.5 mg HCTZ was added as fixed combination once daily for 6 weeks. A 24-hour ambulatory blood pressure monitoring (ABPM) was performed at the end of wash-out and at the end of the fixed-combination period.. No statistically significant difference was found between eprosartan/HCTZ and losartan/HCTZ on the primary endpoint (24-hour ABPM SBP) with an adjusted mean difference between treatments of 3.1 mmHg (95% CI: -0.32-6.59). However, the mean 24-hour ABPM SBP significantly decreased by 16.7 mmHg with eprosartan/HCTZ and 20.3 mmHg with losartan/HCTZ (P<0.001 vs. baseline). The mean Office sitSBP significantly decreased by 28.7 mmHg and 29.6 mmHg respectively, with eprosartan/HCTZ and losartan/HCTZ (P<0.001 vs.baseline and vs. monotherapy).. In this study, eprosartan/HCTZ did not demonstrate to be superior to losartan/HCTZ in reducing ABPM systolic hypertension in the elderly.

Topics: Acrylates; Aged; Analysis of Variance; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure Monitoring, Ambulatory; Diuretics; Double-Blind Method; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Losartan; Male; Office Visits; Severity of Illness Index; Statistics, Nonparametric; Systole; Thiophenes; Treatment Outcome

In an earlier study, our group reported that circulating leucocytes in hypertensive (HT) patients show a significant increase in oxidative stress compared to the control group, and this normalised after two months of treatment with eprosartan.(1) It can be speculated that these facts may be attributable to a possible reduction in anti-oxidative activity in untreated HT patients, which would be corrected by eprosartan.. In this observational pilot study, superoxide dismutase and catalase activities were evaluated in leucocyte lysates in a group of 21 HT patients at baseline and after two months of treatment with eprosartan (600 mg/ day). For the control group, 25 normotensive volunteers were recruited with comparable characteristics to the patients.. The results obtained indicate, paradoxically, that the untreated HT patients present greater anti-oxidant enzyme activity than the control group.. This result could be interpreted as a cell defence mechanism against the greater oxidative stress that exists in these patients.This hypothesis is consistent with the facts reported previously by our group in which a reduction in oxidative stress was found after two months of treatment with eprosartan.( 1) Upon reducing this stress, less anti-oxidative activity would be necessary, just as was observed in the present study after two months of treatment with eprosartan.

Topics: Acrylates; Antihypertensive Agents; Antioxidants; Blood Pressure; Catalase; Cell Extracts; Female; Heart Rate; Humans; Hypertension; Imidazoles; Leukocytes; Male; Middle Aged; Superoxide Dismutase; Thiophenes

Diuretics are considered to be agents of first choice when treating hypertension in the elderly because of their clinical efficacy and, in particular, their low cost. Indeed, the latter consideration has been used by health resource managers to promote the use of diuretics. However, when considering the costs of treating hypertension in a population it is also necessary to assess the adverse effects that diuretics produce, particularly in elderly people.. To compare the overall expenditure associated with the treatment of hypertension (specifically the angiotensin II type 1 receptor antagonist eprosartan vs diuretics) in an elderly population, taking into consideration not only the drug acquisition costs but also the adverse effects of treatment and the costs associated with such adverse effects.. This was a prospective, observational, nonrandomized, open-label, multicentre study based in eight community health centres and the Hypertension Unit of the University Hospital of Salamanca, Spain. The study included 220 hypertensive geriatric outpatients (males and females aged >or=65 years) referred from general practitioners and the Hypertension Unit, with a mean age of 71.8 years and distributed into two groups: one (n = 90) treated with diuretics and the other (n = 130) treated with eprosartan. Following an initial clinical assessment of patients at the beginning of the study, monitoring of treatment continued for 1 year with follow-up consultations scheduled for 3, 6 and 12 months. Both the costs relating to acquisition of the drugs and the costs derived from secondary adverse effects of drug treatment were included in the analysis.. The response to the antihypertensive therapy was similar in both groups. In patients taking diuretics, adverse events resulted in increased use of healthcare resources because of urinary incontinence, purchase of adsorbents, hyponatraemia and the need to admit two patients to hospital. The patient/day cost was euro 1.05 for the group treated with diuretics and euro 0.98 for the group treated with eprosartan (year of costing 2006).. In the geriatric population, the acquisition cost of the prescribed diuretics is not representative of the actual antihypertensive treatment expenditure. According to the results obtained in our study, the overall costs of eprosartan therapy were no different to those of diuretics, despite the fact that eprosartan had a higher acquisition cost. This is consistent with a more favourable safety profile for eprosartan, which may possibly contribute to improved prescription compliance. This conclusion should be taken into consideration when evaluating economic restrictions on the use of drugs.

Topics: Acrylates; Aged; Angiotensin II Type 1 Receptor Blockers; Blood Pressure; Costs and Cost Analysis; Diuretics; Female; Geriatrics; Humans; Hypertension; Imidazoles; Male; Thiophenes

The aim of this study was to compare the effect of telmisartan and eprosartan on insulin sensitivity in overweight hypertensive patients. Fifty overweight (BMI > or = 25 and <30 kg/m (2)) outpatients, aged 41-65 years, with mild to moderate hypertension [systolic blood pressure (SBP) >140 and diastolic blood pressure (DBP) > or = 90 and < or = 110 mmHg], after a 4-week placebo period, were randomized to receive telmisartan 80 mg or eprosartan 600 mg for 8 weeks. Following another 4-week placebo period, patients were crossed to the alternative regimen for further 8 weeks. At the end of each placebo and active treatment period, blood pressure (BP), insulin sensitivity (by euglycemic hyperinsulinemic clamp), fasting plasma glucose (FPG), insulin (FPI), total cholesterol (TC), LDL-C, HDL-C, and triglycerides (Tg) were evaluated. Insulin sensitivity was expressed as the amount of glucose infused during the last 30 min (glucose infusion rate, GIR) in micromol/min/kg. Both telmisartan and eprosartan significantly reduced SBP/DBP values (by a mean of 19.4/13.3 mmHg and 17.9/12.1 mmHg respectively, all p<0.001 vs. placebo), with no significant difference between the two treatments. GIR was significantly increased by telmisartan (2.25+/-0.61 micromol/min/kg, p<0.05 vs. placebo) but not by eprosartan (0.25+/-0.14 micromol/min/kg, p=ns), the difference between the two drugs being statistically significant (p<0.02). No change in FPG, FPI, HDL-C, and Tg was observed with either treatment. Telmisartan significantly reduced TC (-9.9 mg/dl, -5%, p<0.04 vs. placebo) and LDL-C (-8.8 mg/dl, -7%, p<0.03 vs. placebo), whereas eprosartan did not influence them. These findings indicate a superiority regarding an improvement of insulin sensitivity and plasma lipid profile in overweight hypertensives by telmisartan as compared to eprosartan, possibly related to the selective stimulating PPAR-gamma property of telmisartan.

Topics: Acrylates; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Benzoates; Blood Glucose; Female; Humans; Hypertension; Imidazoles; Insulin; Male; Middle Aged; Overweight; Telmisartan; Thiophenes

Recent studies have indicated a relationship between hypertension and cognitive function but therapeutic trials of antihypertensive therapy on the prevention of cognitive disorders have produced controversial findings.. The Observational Study on Cognitive function And Systolic Blood Pressure Reduction is an open-label trial in 28 countries designed to evaluate the impact of eprosartan-based therapy on cognitive function. The Mini-Mental State Examination was used as a global tool for the comprehensive assessment of cognitive function, with an intention to treat a cohort of 25 745 hypertensive patients aged at least 50 years during a follow-up interval of 6 months. Blood pressure therapy was initiated with eprosartan 600 mg/day with provision for additional medication to be introduced after 1 month in patients with insufficient blood pressure response.. Use of eprosartan, either as monotherapy or in combination regimens, was associated with a substantial reduction in arterial blood pressure from 161.9/93.1 mmHg at baseline to 136.1/80.8 mmHg at 6 months (P < 0.0001). The overall mean Mini-Mental State Examination score at completion of follow-up was 27.9 +/- 2.9 compared with 27.1 +/- 3.4 at baseline (P < 0.0001). A significant correlation was shown between the mean absolute response of Mini-Mental State Examination and the magnitude of systolic blood pressure reduction. At the end of the study, patients with systolic blood pressure less than 140 mmHg had a larger improvement in Mini-Mental State Examination [0.88 +/- 0.01 (SEM)] than those with systolic blood pressure between 140 and 159 mmHg [0.69 +/- 0.02 (SEM); P < 0.001], or than those with systolic blood pressure of at least 160 mmHg [0.38 +/- 0.05 (SEM); P < 0.0001]. Furthermore, cognitive decline was demonstrated in multiple linear regression to be independently associated with age [odds ratio 1.19 (1.14; 1.25)], Mini-Mental State Examination at baseline [odds ratio 1.19 (1.14; 1.25)], systolic blood pressure at baseline [odds ratio 1.20 (1.13; 1.27)] and systolic blood pressure reduction [odds ratio 0.77 (0.73; 0.82)].. The results of the Observational Study on Cognitive function And Systolic Blood Pressure Reduction are supportive of the proposition that antihypertensive therapy based on drugs that target the renin-angiotensin system is associated with preservation of cognitive function.

Topics: Acrylates; Aged; Antihypertensive Agents; Blood Pressure; Cognition; Cognition Disorders; Female; Follow-Up Studies; Humans; Hypertension; Imidazoles; Male; Middle Aged; Neuropsychological Tests; Thiophenes; Treatment Outcome

We investigated whether circulating leucocytes from hypertensive patients exhibit more spontaneous, stimulated hydrogen peroxide (H2O2) production and greater mitochondrial membrane potential (Deltapsi) than those from normotensive individuals. We also investigated the effects of oral treatment with the angiotensin II (AT II) type 1 receptor blocker eprosartan (600 mg day(-1)) on these markers of oxidative stress. In 25 hypertensive patients and 28 healthy volunteers, spontaneous H2O2 formation was measured by flow cytometry after preincubation of buffy coat-leucocytes from fresh peripheral venous blood at 37 degrees C with 2',7' dichlorofluorescein. Stimulation of H2O2 formation by circulating leucocytes was elicited by the addition of tert-butylhydroperoxide (tBHP). Deltapsi was determined by flow cytometry after the addition of tetramethylrhodamine methyl ester (TMRM). Compared with healthy individuals, lymphocytes from hypertensive patients exhibited higher Deltapsi (12.28+/-3.20 vs 16.25+/-2.88 arbitrary fluorescence units (AFU), respectively; P<0.001) and greater spontaneous H2O2 production (4.75+/-5.15 vs 8.98+/-9.97 AFU, respectively; P<0.05). tBHP stimulation was associated with higher H2O2 levels in circulating leucocytes in patients with uncorrected hypertension than in normotensive individuals. H2O2 overproduction was corrected by eprosartan treatment. These results suggest that oxidative stress could be important in the pathogenesis of hypertension. Furthermore, measurement of leucocyte oxidant activities may be useful for the evaluation of oxidative stress, which may be reduced with the use of antihypertensive drugs. Our results demonstrate that treatment of hypertension with eprosartan normalizes blood pressure and corrects oxidative disturbances, suggesting that leucocytes could be a target for this drug.

Topics: Acrylates; Adult; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Female; Humans; Hydrogen Peroxide; Hypertension; Imidazoles; Leukocytes; Male; Membrane Potential, Mitochondrial; Middle Aged; Oxidative Stress; Pilot Projects; Rhodamines; tert-Butylhydroperoxide; Thiophenes

Topics: Acrylates; Adrenergic beta-Antagonists; Adult; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Carbazoles; Carvedilol; Dose-Response Relationship, Drug; Drug Therapy, Combination; Exercise Test; Follow-Up Studies; Humans; Hypertension; Imidazoles; Lisinopril; Middle Aged; Propanolamines; Receptor, Angiotensin, Type 1; Thiophenes; Treatment Outcome; Vasodilation

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

It has long been proposed that the renin-angiotensin system exerts a stimulatory influence on the sympathetic nervous system, including augmentation of central sympathetic outflow and presynaptic facilitation of norepinephrine release from sympathetic nerves. We tested this proposition in 19 patients with essential hypertension, evaluating whether the angiotensin receptor blockers (ARBs) eprosartan and losartan had identifiable antiadrenergic properties. This was done in a prospective, randomized, three-way placebo-controlled study of crossover design. Patients were randomized to 600 mg of eprosartan daily, 50 mg of losartan daily, or placebo. The treatment period was 4 wk, with 2-wk washout periods. Multiunit firing rates in efferent sympathetic nerves distributed to skeletal muscle vasculature (muscle sympathetic nerve activity, MSNA) were measured with microneurography, testing whether ARBs inhibit central sympathetic outflow. In parallel, isotope dilution methodology was used to measure whole body norepinephrine spillover to plasma. Mean blood pressure on placebo was 151/98 mmHg, with both ARBs causing reductions of approximately 11 mmHg systolic and 6 mmHg diastolic pressure, placebo corrected. Both MSNA [35 +/- 12 bursts/min (mean +/- SD) on placebo] and whole body norepinephrine spillover [366 +/- 247 ng/min] were unchanged by ARB administration, indicating that the ARBs did not materially inhibit central sympathetic outflow or act presynaptically to reduce norepinephrine release at existing rates of nerve firing. These findings contrast with the easily demonstrable reduction in sympathetic nervous activity produced by antihypertensive drugs of the imidazoline-binding class, which are known to act within the brain to inhibit sympathetic nervous outflow. We conclude that sympathetic nervous inhibition is not a major component of the blood pressure-lowering action of ARBs in essential hypertension.

Topics: Acrylates; Adolescent; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Antihypertensive Agents; Cross-Over Studies; Female; Humans; Hypertension; Imidazoles; Losartan; Male; Middle Aged; Norepinephrine; Renin-Angiotensin System; Sympathetic Nervous System; Thiophenes

Recent data suggest that atenolol may be inferior to other antihypertensive drugs in reducing cardiovascular risk in older individuals with hypertension, despite lowering peripheral blood pressure (BP). We hypothesized that that atenolol fails to reduce central BP as much as other agents. The aim of the present study was to compare the hemodynamic effects of atenolol and eprosartan in a double-blind, randomized, cross-over study.. After a 2-week placebo run-in, 21 subjects with never-treated hypertension underwent 6 weeks of therapy with atenolol (50 mg) and eprosartan (600 mg). Central BP and augmentation index were assessed using pulse wave analysis, and aortic pulse wave velocity was measured, at baseline and at the end of each treatment.. Both drugs reduced peripheral BP to the same degree. However, there was a significantly greater reduction in central systolic BP with eprosartan (means +/- SEM: 16 +/- 3 v 11 +/- 2 mm Hg; P = .03). Despite identical reductions in mean pressure, atenolol reduced aortic pulse wave velocity more than eprosartan (0.8 +/- 0.1 v 0.5 +/- 0.1 m/sec; P = .005). Conversely, augmentation index and N-terminal pro-brain natiuretic peptide levels were reduced significantly after eprosartan (6% +/- 2% and 11 +/- 5 pg/mL, respectively) but were increased after atenolol (7% +/- 2% and 67 +/- 24 pg/mL, respectively).. These data indicate that despite similar effects on peripheral BP and a greater effect on aortic stiffness, atenolol had less impact on central systolic BP than eprosartan because it failed to reduce wave reflection. This provides one potential explanation for the failure of atenolol to improve outcome in older patients with essential hypertension.

Topics: Acrylates; Antihypertensive Agents; Aorta, Thoracic; Atenolol; Blood Pressure; Cross-Over Studies; Double-Blind Method; Electrocardiography; Female; Follow-Up Studies; Humans; Hypertension; Imidazoles; Male; Middle Aged; Prospective Studies; Pulsatile Flow; Receptor, Angiotensin, Type 1; Thiophenes; Treatment Outcome

Antihypertensive drug eprosartan from the group of angiotensin II receptor blockers was studied from the position of its effect on professionally significant psychophysiological qualities of train drivers, which were assessed with the help of psychophysiological tests. One hundred drivers with arterial hypertension were included into the study and 2 adequate groups were distinguished: 1st which consisted of 50 persons receiving eprosartan (600 mg/day), and 2nd which comprised 50 persons receiving placebo. Results of the study have showed that eprosartan did not lower professionally significant psychophysiological qualities of drivers.

Topics: Acrylates; Adult; Angiotensin II Type 1 Receptor Blockers; Humans; Hypertension; Imidazoles; Male; Middle Aged; Occupational Diseases; Railroads; Thiophenes

Studies in animals and humans indicate a role for kinins in the actions of angiotensin type 1 (AT1) receptor blockers. However, the effect of these compounds on kinin levels in humans is unknown.. We measured angiotensin (Ang), bradykinin (BK), and kallidin peptides in subjects with essential hypertension administered placebo, losartan (50 mg OD), and eprosartan (600 mg OD) in randomized order in a double-blind, 3-period, 3-treatment, crossover trial. Peptides were measured in arterial blood using high-performance liquid chromatography-based radioimmunoassays. Losartan increased blood levels of BK-(1-9) and hydroxylated BK-(1-9) by approximately 2-fold and reduced the BK-(1-7)/BK-(1-9) ratio by 55%. There was a trend for eprosartan to produce similar changes in bradykinin levels. There were no changes in blood kallidin levels. Both losartan and eprosartan increased plasma levels of Ang I, Ang II, and Ang-(2-8), and eprosartan increased Ang-(3-8) levels. Ang-(1-7) and Ang-(1-9) levels were unchanged. There was an associated 30% to 35% reduction in Ang II/Ang I ratio and 63% to 69% reduction in Ang-(1-7)/Ang I ratio. Plasma ACE activity was unchanged.. Losartan increases bradykinin levels. The reductions in BK-(1-7)/BK-(1-9), Ang II/Ang I, and Ang-(1-7)/Ang I ratios suggest that the increased bradykinin levels were the result of reduced metabolism by ACE and neutral endopeptidase. Increased bradykinin levels may represent a class effect of AT1 receptor blockers that contributes to their therapeutic actions and may also contribute to the angioedema that may accompany this therapy.

Topics: Acrylates; Adolescent; Adult; Aged; Angiotensin I; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Bradykinin; Chromatography, High Pressure Liquid; Cross-Over Studies; Double-Blind Method; Female; Humans; Hydroxylation; Hypertension; Imidazoles; Kallidin; Losartan; Male; Middle Aged; Peptide Fragments; Radioimmunoassay; Thiophenes

A multicentre, prospective, non-comparative open-label study was conducted to assess the effect of eprosartan, 600 mg/day, on pulse pressure (PP) in patients with hypertension (stage I or II, Joint National Committee, sixth report) treated in the primary care setting, as well as safety and compliance. The duration of treatment was 16 weeks. Eprosartan decreased PP (-13 mmHg), systolic blood pressure (SBP) (-26 mmHg), diastolic blood pressure (DBP) (-13 mmHg) and mean arterial pressure (MAP) (-17.4 mmHg) significantly (p < 0.0001). The PP/MAP ratio changed significantly from 62 to 59%, so that the reduction of PP was 3% higher than the overall decrease in MAP. Twenty adverse events, mostly gastrointestinal complaints, were recorded in 12 patients (1.9%). Compliance with treatment at the end of the study was 94%. Eprosartan was a well-tolerated and an effective drug in reducing PP, SBP and DBP below the recommended levels in patients with mild-to-moderate essential hypertension, allowing a high therapeutic compliance.

Topics: Acrylates; Adult; Aged; Antihypertensive Agents; Blood Pressure; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Prospective Studies; Pulse; Thiophenes; Treatment Outcome

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

To assess the effects of eprosartan and valsartan on the haemodynamics of forearm circulation in hypertensives undergoing isometric and mental stress.. Thirty-six patients with essential stable hypertension underwent haemodynamic evaluations on the left arm: humeral flux and calibre by means of colour Doppler ultrasound, microcirculatory flux on the third finger of left hand by means of laser Doppler flowmetry, blood pressure and heart rate monitor. District resistance was calculated as the ratio between mean arterial pressure and blood flow, and microcirculatory conductance was calculated as the ratio between flux and the mean pressure. The evaluations were performed at rest, during handgrip and during mental stress. Patients were randomized to receive eprosartan (600 mg) or valsartan (160 mg); tests were repeated after 15 days of therapy.. Both treatments reduced blood pressure (P<0.05) and peripheral resistance during tests. Eprosartan obtained a greater reduction in resistance during handgrip than valsartan. Laser Doppler flowmetry showed a significant decrease of flux only with mental stress. Laser Doppler flowmetry showed a reduction in conductance during both tests--this reduction was smaller with eprosartan during handgrip. None of the molecules affected the conductance during mental stress. While both were able to reduce microcirculatory decrease in conductance; in particular, eprosartan controlled this drop during handgrip better than valsartan.. Angiotensin II receptor type 1 inhibition exerts protective effects during adrenergic and noradrenergic stress in hypertensives. Eprosartan is more efficacious than valsartan in controlling noradrenergic effects.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Female; Forearm; Hand Strength; Heart Rate; Humans; Hypertension; Imidazoles; Laser-Doppler Flowmetry; Male; Microcirculation; Middle Aged; Skin; Stress, Psychological; Tetrazoles; Thiophenes; Time Factors; Treatment Outcome; Valine; Valsartan

The use of eprosartan (600-1200 mg/day for 4 weeks) in 28 patients with stage II hypertensive disease was associated with improvement of parameters of microcirculation and blood rheology.

Topics: Acrylates; Adult; Antihypertensive Agents; Female; Humans; Hypertension; Imidazoles; Male; Microcirculation; Middle Aged; Rheology; Thiophenes; Treatment Outcome

Patients with left ventricular ejection fraction below 45% (mean 39+/-3.7%) were randomized either to captopril (n=33) or eprosartan after miocardial infarction (n=33) on days 3-7 of myocardial infarction. All patients were subjected to echocardiography and 40 to perfusion myocardial scintigraphy with (99m)TC-Technetril. Myocardial viability was defined as presence of perfusion reserve in dysfunctional segments during test with nitroglycerin. Dysfunctional myocardium was found to be viable in 62.5% of patients. Fifty six patients completed 3 months follow up and were restudied. By the time of the second study 28 patients continued captopril (37.5-150 mg, average dose 72+/-34.2 mg/day) and 28 - eprosartan (300-600 mg, average dose 471+/-151 mg/day). Captopril was stopped or its dose corrected in 28% of patients. In eprosartan group there were no side effects which required withdrawal of the drug. Similar increases of ejection fraction occurred on both groups (from 38+/-2.1 to 49+/-6.7%, p<0.001 and from 39+/-4 to 51+/-6.5%, p<0.001, in eprosartan and captopril groups, respectively). Magnitude of left ventricular ejection fraction change did not depend on the presence of viable myocardium. However in both treatment groups improvement of myocardial perfusion and decrease of left atrial dimensions were found only in patients with viable myocardium at initial study.

Topics: Acrylates; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Severity of Illness Index; Systole; Thiophenes; Ventricular Dysfunction, Left

This was a double-blind, randomized, placebo-controlled multicenter, titration-to-effect study of eprosartan in patients > or =60 years of age with isolated systolic hypertension. The study consisted of a 3 to 5-week placebo run-in period, a 13-week double-blind treatment period (6-week titration with eprosartan 600-1200 mg/day, 3-week maintenance, 4-week combination therapy with hydrochlorothiazide/HCTZ 12.5 mg), and a follow-up period within 5-7 days of last treatment dose. Overall, 283 patients (placebo/P: 135; eprosartan /E: 148) were randomized [female patients-P: 55.6%, E:54.7%; white-P:66.7%, E:67.6%). Mean sitting systolic blood pressure (SitSBP) at baseline was comparable (P: 170+/-0.8 mmHg; E: 171+/-0.8 mm Hg). At monotherapy end point, eprosartan produced a significant reduction in SitSBP (E: 16.1 mmHg vs P: 8.4 mmHg; P<0.0001). In all, 57.4% of patients responded to eprosartan monotherapy. Among nonresponders, the addition of HCTZ resulted in a decrease in SitSBP from baseline (E: 21.7 mmHg; P: 14.4 mmHg; P<0.002). Reductions were also noted in Standing SBP (monotherapy: P<0.001; combination therapy: P=0.03). No reductions in SitDBP >4 mmHg were found during the study. Age, gender, and race did not have any impact on the results. Post hoc analysis showed a reduction in pulse pressure from 87.3 to 78.2 mmHg with placebo and from 87.6 to 70.7 mmHg with eprosartan monotherapy. Treatment with eprosartan in once-daily doses up to 1200 mg alone or in combination with HCTZ was well tolerated, with dizziness and asthenia being the most common side effects.

Topics: Acrylates; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Heart Rate; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Male; Middle Aged; Sodium Chloride Symporter Inhibitors; Thiophenes; Treatment Outcome

We evaluated the antihypertensive activity, glucose homeostasis and plasma lipid profile in patients with mild hypertension and type 2 diabetes mellitus treated by diet and exercise, and not in receipt of oral hyperglycemics, following 12-month treatment with either telmisartan or eprosartan. In this double-blind, placebo-controlled trial, 119 patients with mild essential hypertension (diastolic blood pressure [DBP] 91-104 mmHg) and type 2 diabetes were divided into three groups and randomized to receive once-daily telmisartan 40 mg, eprosartan 600 mg, or placebo for 12 months. At enrollment, patients were advised on diet (1,400-1,600 kcal/day) and exercise (physical aerobics on a bicycle for at least 30 min on 4 days each week). Compared with baseline, a significant reduction (p<0.01) in seated trough systolic blood pressure (SBP) was detected after 12-month treatment with either telmisartan or eprosartan. Seated trough DBP was also reduced by telmisartan (p<0.01) and eprosartan (p<0.05); the antihypertensive effect of telmisartan was significantly superior (p<0.05). No change in body mass index or glucose metabolism was observed with either active treatment, or with placebo. Telmisartan, but not eprosartan, significantly improved plasma total cholesterol (p<0.01), low-density lipoprotein cholesterol (p<0.01) and triglycerides (p<0.05) compared with eprosartan. In conclusion, 12-month telmisartan treatment produced a significantly greater reduction in DBP than eprosartan and significantly improved plasma lipids. The improvement could be due to varying pharmacokinetic/pharmacodynamic properties of telmisartan compared with eprosartan, even if it is not clear about the relationship between angiotensin-II receptor blockade and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Benzoates; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Female; Glucose; Homeostasis; Humans; Hypertension; Imidazoles; Lipids; Male; Middle Aged; Telmisartan; Thiophenes

The renin-angiotensin system is the major contributor to development of hypertension, atherosclerosis, and many other cardiovascular diseases. Angiotensin II, one of the main effectors of this system, contributes to the pathogenesis of hypertension and plays an important role in monocyte, platelet, and endothelium interactions. The effects on platelet and endothelial function, either by angiotensin converting enzyme inhibitors or angiotensin receptor antagonists, are still not well understood. A double-blind, randomized, prospective trial of either enalapril (10-20 mg daily) or eprosartan (400-800 mg daily) over a 10-week period was conducted in 42 patients (27 males, 15 females). Platelet activation was evaluated by measuring platelet factor 4 (PF-4), beta-thromboglobulin (beta-TG), the ratio of platelet factor 4 to beta-thromboglobulin, and endothelial function by measuring total plasma nitrate levels, von Willebrand factor (vWF) levels, and blood flow using venous occlusive plethysmography. After a 10-week treatment with enalapril or eprosartan, the sitting blood pressure in both the enalapril group (from 152.2 +/- 18.7 mmHg to 141.9 +/- 23.5 mmHg, P < 0.05) and eprosartan group (from 151 +/- 10.0 mmHg to 142.3 +/- 12.9 mmHg, P < 0.05) was significantly reduced. Significant diastolic blood pressure (DPB) reduction (from 94 +/- 8.7 to 84.5 +/- 9.6 mmHg, P < 0.05) and a greater DBP reduction response were found in the eprosartan group (63% in eprosartan versus 25% in enalapril). Additionally, dose-dependent reductions in the indices of platelet activation and endothelial dysfunction were observed in patients administered high dose treatments of eprosartan and enalapril, and the beneficial effects of these agents were not correlated with the reduction of blood pressure using both agents. Eprosartan is effective and well-tolerated in the treatment of mid-to-moderate hypertension, and the DBP response reduction to eprosartin was better than that to enalapril. A high dose of either eprosartan or enalapril significantly decreased the indices of platelet activation and endothelial dysfunction in hypertensive patients. The benefits of both agents cannot be explained solely by their antihypertensive effects and possibly may be mediated through their unique effect on angiotensin blockade.

Topics: Acrylates; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Enalapril; Endothelium, Vascular; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Platelet Activation; Prospective Studies; Thiophenes

Hypertensive patients show greater platelet activation than do normotensive individuals. Platelet activation is characterized by increased phosphatidylserine (PS) exposure in the external hemilayer of the membrane, a larger number of platelet microparticles (PMP), and changes in intraplatelet-free calcium kinetics. This study evaluated whether eprosartan can protect against undesirable platelet activation.. A total of 30 hypertensive patients (systolic blood pressure [SBP] 140 to 189 mm Hg; diastolic blood pressure [DBP] 90 to 109 mm Hg) without renal, liver, or cardiac organic lesions and with a mean age of 47.6 +/- 9.4 years and mean body mass index (BMI) of 27.9 +/- 3.9 kg/m2 received eprosartan (600 mg/day). They were compared with 31 normotensive individuals with a mean age of 43.3 +/- 6.7 years and a mean BMI of 26.8 +/- 3.9 kg/m2. Blood pressure measurements and platelet function changes were assessed at baseline (control and hypertensive patients) and after 1 and 2 months of eprosartan monotherapy (hypertensive patients only).. Significant baseline to endpoint (month 2) changes in SBP and DBP were noted in the eprosartan group (SBP: baseline 152.2 +/- 16.8 mm Hg, endpoint 142.2 +/- 16.9 mm Hg, P <.01; DBP: baseline 93.5 +/- 9.9 mm Hg, endpoint 85.8 +/- 11.9 mm Hg, P <.001). Native circulating activated platelets increased in both groups after shear stress or Ca2+ ionophore activation, and were reduced by eprosartan (after shear exposure from 104% at month 1 to 76% after 2 months of therapy). Eprosartan therapy normalized the number of microparticles after blood shear exposure (P <.01) and after exposure to Ca2+ ionophore activation (P <.05) and significantly reduced the trend for platelets to be more readily activated in hypertensive compared with normotensive subjects (baseline to endpoint change P <.001; increase/shear versus baseline P <.001). Eprosartan partially normalizes cytoplasmic-free calcium mobilization in platelets.. Eprosartan significantly reduces blood pressure and normalizes undesirable changes in platelet function.

Topics: Acrylates; Adult; Antihypertensive Agents; Blood Pressure; Calcium; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Particle Size; Platelet Activation; Prospective Studies; Stress, Mechanical; Thiophenes

Essential hypertension is often accompanied by abnormalities of the coagulation/fibrinolytic system predisposing to a procoagulant state. The aim of the present study was to examine the comparative efficacy of the angiotensin II type 1 receptor antagonists eprosartan and losartan on plasma levels of hemostatic/fibrinolytic and endothelial function markers in a cohort of previously untreated hypertensive patients. A total of 86 patients whose hypertension was controlled by monotherapy with eprosartan 600 mg (45 patients) or losartan 100 mg (41 patients) were studied. The plasma levels of plasminogen activator inhibitor-1 (PAI-1) antigen, tissue plasminogen activator inhibitor (tPA) antigen, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI) antigen, and fibrinogen were determined before and after 6 months of therapy. Age, sex distribution, body mass index, lipid profile, systolic and diastolic blood pressure levels, and baseline values of the measured markers were similar in both groups. After 6 months of therapy, systolic blood pressure was significantly lower in patients treated with eprosartan, while no differences were observed with respect to diastolic blood pressure. Treatment with both drugs was associated with a significant decrease in PAI-1 antigen, TM, fibrinogen plasma levels and an increase in tPA antigen. The favorable modification of all the above parameters was significantly greater in the eprosartan than in the losartan group, while TFPI plasma levels were decreased to a similar extent with both drugs. In conclusion, the results of our study indicate that 6-month monotherapy with a new angiotensin II type 1 receptor blocker, eprosartan, is associated with a more favorable modification of hemostatic/fibrinolytic status than with losartan.

Topics: Acrylates; Aged; Angiotensin II Type 1 Receptor Blockers; Drug Administration Schedule; Female; Fibrinogen; Fibrinolysis; Follow-Up Studies; Hemostasis; Humans; Hypertension; Imidazoles; Lipoproteins; Losartan; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Receptor, Angiotensin, Type 1; Thiophenes; Thrombomodulin; Time Factors; Tissue Plasminogen Activator

Evidence suggests that antihypertensive agents may have differential effects on systolic blood pressure (SBP) and that home BP monitoring (HBPM) may enhance the antihypertensive effects.. To evaluate the efficacy and safety of eprosartan mesylate in the treatment of hypertension, particularly on SBP in older subjects, and to assess the role of HBPM.. A randomized, open-label, 10-week study was conducted in 35 primary care centres across Canada. One hundred ninety-eight subjects (aged 60 to 84 years) with mild to moderate hypertension (SBP 140 mmHg to 179 mmHg, diastolic BP [DBP] 109 mmHg or less) were included in the analysis. All subjects received open-label eprosartan mesylate 600 mg once daily, and were randomly assigned to eprosartan treatment alone or eprosartan plus HBPM. Hydrochlorothiazide 12.5 mg once daily could be added after week 4. The primary outcomes were the change in SBP at study end and the effect of HBPM on SBP.. In the eprosartan and eprosartan plus HBPM groups, SBP was reduced by 17.6 mmHg and 19.9 mmHg, and DBP was reduced by 8.7 mmHg and 8.5 mmHg, with a systolic pressure response of 58% and 65%, respectively. HBPM had no additional benefits. Eprosartan was well tolerated, with the majority of adverse events being mild to moderate.. Eprosartan alone or in combination with hydrochlorothiazide was highly effective and safe in lowering blood pressure, notably SBP, in older subjects with mild to moderate hypertension.

Topics: Acrylates; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Blood Pressure Determination; Canada; Diastole; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Male; Middle Aged; Primary Health Care; Probability; Prospective Studies; Reference Values; Severity of Illness Index; Single-Blind Method; Systole; Thiophenes; Treatment Outcome

Isolated systolic hypertension (ISH) is a common and particularly poorly controlled form of hypertension.. To assess the effect of eprosartan 600 mg tablet once daily on blood pressure (BP), pulse pressure, BP response, compliance and safety in subjects with ISH compared with subjects with combined systolic-diastolic hypertension (non-ISH).. The present study is a post hoc evaluation of a prospective, randomized, open-label, multicentre study. Subjects 60 to 84 years old with ISH (systolic BP 140 mmHg or greater with diastolic BP less than 90 mmHg) (n=97) or non-ISH (systolic BP 140 mmHg or greater with diastolic BP 90 mmHg or greater) (n=98) received 10 weeks of treatment with either eprosartan alone or eprosartan plus home BP monitoring.. Eprosartan significantly reduced systolic BP at the study end point from baseline in both the ISH group and the non-ISH group (-17.5+/-14.5 mmHg and -20.6+/-14.1 mmHg [mean +/- SD], respectively; P<0.0001). The reduction in diastolic BP was significantly greater in subjects with non-ISH than in those with ISH (-12.2+/-8.1 mmHg and -5.0+/-7.9 mmHg, respectively; P<0.0001). Mean pulse pressure was significantly reduced from baseline in both groups (P<0.0001), but was reduced to a significantly greater degree in the ISH group than in the non-ISH group (-12.5+/-12.3 mmHg and -8.4+/-11.1 mmHg, respectively; P<0.05). The most common adverse events were dizziness, headache and fatigue.. Eprosartan effectively lowered BP and pulse pressure in all subjects. The magnitude of pulse pressure reduction was significantly greater in the ISH group, and the diastolic BP reduction was greater in the non-ISH group, suggesting that eprosartan may be especially suitable in the treatment of subjects with ISH.

Topics: Acrylates; Administration, Oral; Age Factors; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Blood Pressure; Blood Pressure Determination; Canada; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hypertension; Imidazoles; Male; Middle Aged; Probability; Reference Values; Severity of Illness Index; Systole; Thiophenes; Treatment Outcome

The aortic pulse wave contour in isolated systolic hypertension often shows a prominent reflection peak, which combines with the incident wave arising from cardiac ejection so as to widen pulse pressure. We investigated the effects of an extended-release nitrate preparation and of 2 angiotensin II (AII) inhibitors (an AII receptor antagonist and an ACE inhibitor) on the aortic pulse wave contour and systemic blood pressure in hypertensive subjects with high augmentation index caused by exaggerated pulse wave reflection. Two double-blind, randomized, placebo-controlled crossover studies were carried out in a total of 16 elderly patients with systolic hypertension resistant to conventional antihypertensive therapy. In 1 study, pharmacodynamic responses to single doses of placebo, isosorbide mononitrate, eprosartan, and captopril were determined; in the other, single-dose isosorbide mononitrate and placebo were compared in subjects treated with AII inhibitors at baseline. Blood pressure was measured by sphygmomanometry and pulse wave components by applanation tonometry at the radial artery. All 3 agents were shown to decrease brachial systolic blood pressure, aortic systolic blood pressure, and aortic pulse pressure. Qualitative effects on the aortic pulse wave contour differed: augmentation index was not significantly altered by either captopril or eprosartan but was decreased (P<0.0001) by approximately 50% of the placebo value with isosorbide mononitrate in both study groups. We propose that isosorbide mononitrate corrected the magnified wave reflection in systolic hypertension of these elderly patients by an effect that was distinct from that exercised by either acute or chronic AII inhibition.

Topics: Acrylates; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Captopril; Cross-Over Studies; Delayed-Action Preparations; Double-Blind Method; Female; Heart Rate; Humans; Hypertension; Imidazoles; Isosorbide Dinitrate; Male; Middle Aged; Pulse; Thiophenes; Time Factors; Vasodilator Agents

To elucidate the effect of the angiotensin type 1 (AT1) receptor antagonist (AT1RA) eprosartan (E) on renal hemodynamics in normotensive and borderline hypertensive subjects, we investigated the hormonal and renal hemodynamic responses during cardiopulmonary stress testing.. In a prospective, double-blind, randomized, placebo-controlled crossover study, the effects of E on renal plasma flow (RPF), renal blood flow (RBF), glomerular filtration rate (GFR), and the concentration of angiotensin II (Ang II) levels were measured with the subjects at rest and during perturbation of cardiopulmonary baroreceptors using lower body negative pressure (LBNP). Ten normotensive male subjects (NT) versus 14 males with mild hypertension (HT), matched for age and body mass index, who were all free of any medication, were randomly assigned to receive placebo or E 600 mg/day PO for seven days (intake phase 1). After a washout period of four weeks the subjects started the intake of the other substance for seven days in a crossover manner (intake phase 2). The measurements were taken on day 7 of both intake phases.. During the LBNP test, RPF and RBF were reduced significantly in all subjects; GFR, however, decreased significantly during cardiopulmonary stress testing in the subjects taking the placebo (P < 0.05) and remained unchanged in those under treatment with AT1RA. Ang II levels increased significantly during cardiopulmonary stress test only in the subjects with hypertension who were on placebo, whereas the Ang II levels did not change in normotensive subjects or those treated with the AT1RA.. The data confirm that with cardiovascular stress simulating orthostasis or volume depletion, subjects with AT1RA can maintain their GFR level, suggesting that AT1RA potentially is renoprotective. Additionally, the neurohumoral system is activated after cardiovascular stress in subjects even at an early stage of hypertension.

Topics: Acrylates; Adult; Angiotensin II; Angiotensin Receptor Antagonists; Blood Pressure; Cross-Over Studies; Double-Blind Method; Endocrine Glands; Glomerular Filtration Rate; Hemodynamics; Humans; Hypertension; Imidazoles; Lower Body Negative Pressure; Male; Renal Circulation; Severity of Illness Index; Thiophenes

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

Asymmetrical N(G), N(G)-dimethylarginine (ADMA) is associated with impaired endothelium-dependent vasodilation in humans.. Twenty young, male, mildly hypertensive subjects were included in a randomized, double-blind, fourfold cross-over study with placebo, enalapril (20 mg/day), eprosartan (600 mg/day), or a combination of both drugs (10 and 300 mg/day, respectively) each over 1 week, followed by a 2-week wash-out phase. After each treatment phase, ADMA concentration was measured.. ADMA concentration was 1.69+/-0.59 micromol/L in the placebo phase, and was significantly lower in the enalapril, eprosartan, and combination phases (1.41+/-0.29, 1.42+/-0.43, and 1.38+/-0.30 micromol/L, respectively; all P < 0.05 v placebo). Changes in ADMA levels were independent of the drugs' action on blood pressure (BP).. Levels of ADMA were reduced with enalapril and eprosartan therapy. Our results suggest a specific action of these drugs on ADMA levels that is independent of BP.

Topics: Acrylates; Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arginine; Blood Pressure; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Enalapril; Endothelium, Vascular; Humans; Hypertension; Imidazoles; Male; Receptor, Angiotensin, Type 1; Thiophenes

Serum urate is commonly elevated in essential hypertension (26-33%). Some studies have claimed that losartan increases urinary uric acid excretion and diminishes serum urate levels. However, a detailed, controlled study on the influence of losartan on uric acid metabolism in hypertensive patients has not been performed and the existent results are conflicting. Two small studies claimed that losartan reduced serum urate levels but only one showed a simultaneous increased uric acid excretion rate. The development of several AT1 receptor blockers raises the question whether these antihypertensive drugs influence uric acid metabolism.. In a randomized, prospective (4 weeks), double blind, parallel study we have compared the influence of losartan (50 mg/day) versus eprosartan (600 mg/day) on uric acid metabolism in 58 patients with mild to moderate essential hypertension. The mean uric acid to creatinine ratio change from baseline at 4 weeks was +0.11 for losartan and -0.04 for eprosartan (P < 0.01). The mean increase in 24-h urinary uric acid excretion with losartan was +0.7 mmol/24 h (25% increase from baseline). The change in serum urate levels versus baseline was similar after 4 weeks with losartan (-23.4 mumol/l) and eprosartan (-19.5 mumol/l). Patients with hyperuricemia in both treatment groups showed similar modifications of uric acid metabolism compared with non-hyperuricemic subjects. Blood pressure control was achieved in 22 patients (73%) with eprosartan and in 16 (53%) with losartan.. Losartan increased uric acid excretion in hypertensive patients but eprosartan did not. Neither AT1 receptor antagonist substantially modified serum urate concentrations.

Topics: Acrylates; Angiotensin Receptor Antagonists; Antihypertensive Agents; Double-Blind Method; Humans; Hypertension; Imidazoles; Losartan; Receptor, Angiotensin, Type 1; Thiophenes; Uric Acid

Topics: Acrylates; Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cholesterol; Endothelium, Vascular; Fibrin; Humans; Hypertension; Imidazoles; Male; Receptors, Angiotensin; Thiophenes

This randomised, double-blind study was designed to investigate the efficacy of a once-daily (OD) combination of the AT(1) receptor blocker, eprosartan 600 mg, and the thiazide diuretic, hydrochlorothiazide (HCTZ) 12.5 mg, in patients with mild to moderate hypertension (sitting diastolic blood pressure (sitDBP) > or =98 mm Hg and < or =114 mm Hg) not adequately controlled with eprosartan 600 mg OD. A total of 494 patients entered the open-label monotherapy run-in phase, which consisted of eprosartan 600 mg OD for 3 weeks. Patients who responded to monotherapy were not eligible to enter the randomised phase of the study and were withdrawn. The remaining 309 patients were then randomised to either eprosartan 600 mg plus HCTZ 12.5 mg OD or to continue on eprosartan 600 mg OD. In the eprosartan plus HCTZ combination group, both sitDBP and sitting systolic blood pressure (sitSBP) were significantly reduced compared with the eprosartan monotherapy group. In addition, the response rate was higher in the combination group compared with the monotherapy group. There were no significant effects on reduction of sitDBP due to gender, prior use of antihypertensives or baseline severity of hypertension. The tolerability profile for the combination group was similar to that for the monotherapy group. Headache was the most frequent adverse event in both treatment groups. The majority of adverse events were mild to moderate in intensity. In this study of patients who were unresponsive to eprosartan monotherapy for 3 weeks, a combination product of eprosartan 600 mg and HCTZ 12.5 mg was shown to be an effective and well tolerated treatment.

Topics: Acrylates; Adult; Aged; Antihypertensive Agents; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Male; Middle Aged; Prospective Studies; Thiophenes

Experimental data in humans on the contribution of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers to the nitric oxide system of the renal vasculature are inconsistent. Enalapril and eprosartan, alone and in combination, were used to determine their short-term effects on the renal nitric oxide system and renal hemodynamics of human subjects with essential hypertension.. Twenty male, white patients (27 +/- 1 years) with mild essential hypertension (143 +/- 11/95 +/- 6 mm Hg) were included in a double-blind, randomized, placebo-controlled, fourfold cross-over study with placebo, enalapril (20 mg/day), eprosartan (600 mg/day), or combination of both drugs (10 and 300 mg/day, respectively) each over a one week period followed by a two-week washout phase. After each study phase the glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined. Basal nitric oxide synthesis of the renal vasculature was assessed by the decrease in RPF after inhibition of nitric oxide synthase with NG-monomethyl-L-arginine (L-NMMA; 4.25 mg/kg).. After one week of therapy, the combination therapy decreased casual blood pressure by 5 +/- 2/3 +/- 1 mm Hg versus placebo (P < 0.01). Neither enalapril alone (-2 +/- 2/1 +/- 2 mm Hg, NS vs. placebo) nor eprosartan alone (-1 +/- 1/0 +/- 2 mm Hg, NS vs. placebo) had a clear-cut significant effect on casual blood pressure. In the combination phase, RPF increased by 123 +/- 36 mL/min (P < 0.01). Neither enalapril alone (+59 +/- 46 mL/min, P = 0.21) nor eprosartan alone (+113 +/- 51 mL/min, P = 0.06) had a clear-cut significant effect on RPF. Changes of RPF induced by treatment correlated with the L-NMMA induced decrease in RPF in the combination (r = 0.70, P < 0.01) and eprosartan phase (r = 0.86, P < 0.001), but not in the enalapril phase (r = -0.44, P = 0.10). Renal vascular resistance was reduced by each active treatment with the most prominent reduction in the combination phase. GFR was unaffected by any treatment.. In contrast to the effects of either substance alone, a combination of half the dose of eprosartan with half the dose of enalapril had a prominent effect on renal perfusion. The effects of eprosartan on RPF are mediated, at least in part, by an increased bioavailability of nitric oxide in the renal vasculature.

Topics: Acrylates; Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Blood Vessels; Double-Blind Method; Drug Combinations; Enalapril; Enzyme Inhibitors; Hemodynamics; Humans; Hypertension; Imidazoles; Male; Nitric Oxide; omega-N-Methylarginine; Receptor, Angiotensin, Type 1; Renal Circulation; Thiophenes

Control of hypertension is hindered by the incidence of adverse events associated with therapy, which can result in low patient compliance. Specific angiotensin II receptor subtype AT1 blockers offer an alternative to the angiotensin converting enzyme inhibitors in the treatment of hypertension, as the incidence of side-effects may be lower. This open-label study was designed to investigate the long-term safety and efficacy of the AT1 receptor blocker, eprosartan, in patients with mild to moderate essential hypertension (sitting diastolic blood pressure > or = 95 mmHg and < or = 114 mmHg). 706 patients from 55 centres in the USA and three centres in Canada were randomised to receive once-daily eprosartan (400-800 mg) alone or in combination with hydrochlorothiazide (HCTZ). The study consisted of five periods: screening (day 1), run-in (2-4 weeks), titration (3-15 weeks), maintenance (12-24 months) and follow-up (5-7 days). Safety evaluations included incidences of adverse events and changes in laboratory tests, vital signs and electrocardiograms. Efficacy assessments included effects on blood pressure (BP) and fasting concentrations of lipids and glucose. The maintenance period was completed at 12 months by 583 (83.3%) patients and at 24 months by 311 (44.4%) patients. In total, 396 (56.1%) patients completed the study according to protocol. Once-daily eprosartan was well tolerated either alone or in combination with HCTZ, irrespective of the study dose administered. Patients treated with eprosartan had a safety profile similar to that reported in short-term placebo-controlled studies. The most frequently reported adverse event was upper respiratory tract infection. The incidence of adverse events was not affected by age or race, and, although events increased with the addition of HCTZ, they were generally not severe. The beneficial effect on BP was maintained throughout treatment. For the majority of patients, HDL cholesterol, triglyceride and glucose levels remained within the reference levels at all doses and timepoints. In summary, eprosartan provides reliable blood pressure control in a high proportion of patients, with a safety profile similar to that seen with placebo in short-term, placebo-controlled trials. By providing long-term safety and efficacy, eprosartan may have the potential to increase patient compliance, a significant issue in the treatment of hypertension in all patient types.

Topics: Acrylates; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Canada; Diuretics; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Male; Middle Aged; Severity of Illness Index; Sodium Chloride Symporter Inhibitors; Thiophenes; Treatment Outcome; United States

The objective of this study was to compare quality of life and incidence of dry persistent cough among patients treated with eprosartan and enalapril for mild-moderate hypertension. This was a randomised 26-week double-blind controlled trial carried out in clinics in nine countries of North America, Europe and South Africa. A total of 529 patients aged 18 and over with diastolic blood pressure between 95 mm Hg and 114 mm Hg were studied. Treatment comprised of eprosartan or enalapril monotherapy for 12 weeks with the option of hydrochlorothiazide addition for the remaining 14 weeks. The primary outcome measures were cough and the Psychological General Wellbeing Index (PGWB) total and subscales (anxiety, self-control, depression, general health, positive wellbeing and vitality). The results were that 17.8% of enalapril patients and 13.2% of eprosartan patients withdrew from randomised treatment. Those on enalapril were twice as likely to have gained a definite or possible cough by study end point as those on eprosartan (7.6% vs 3.2%) P = 0.099. At monotherapy end point the differences were greater (9.9% vs 2.1%) and of statistical significance, P = 0.001. Patients treated with enalapril, however, had small but significant improvements in measures of self-control and total PGWB compared with those on eprosartan. The effect sizes of 0.2 or less indicated that there were small differences. In conclusion eprosartan was associated with fewer coughs than enalapril but it performed less well on some aspects of quality of life.

Topics: Acrylates; Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Cough; Double-Blind Method; Drug Administration Schedule; Enalapril; Europe; Female; Follow-Up Studies; Humans; Hypertension; Imidazoles; Incidence; Male; Middle Aged; North America; Probability; Prospective Studies; Quality of Life; Risk Factors; Severity of Illness Index; South Africa; Thiophenes; Treatment Outcome

The objective of this study was to compare the quality of life and incidence of dry cough with the angiotensin II antagonist eprosartan, the ACE-inhibitor enalapril, and placebo, in hypertensive patients with a history of ACE-inhibitor cough. The study was a multicentre, randomised, double-blind, parallel group controlled trial. A total of 136 patients judged to have ACE-inhibitor cough during single-blind enalapril treatment which was lost during a subsequent placebo washout phase, were randomised to receive either eprosartan 300 mg twice daily, or enalapril 20 mg once daily, or placebo for 6 weeks. Self-completion questionnaires assessing quality of life and cough were examined at baseline and end of study. At study end point 23% of patients in the enalapril group and 5% in the eprosartan and placebo groups reported cough (which included definite, probable and possible coughs) (P = 0.02). After adjusting for multiple comparisons, the eprosartan group was not significantly different from either placebo or enalapril. There were no significant differences in the Psychological General Wellbeing Index (PGWB). In conclusion the incidence of self-reported cough on eprosartan was similar to that on placebo, and lower than on enalapril but this difference was not significant when adjustments were made for multiple comparisons. There were no differences in quality of life.

Topics: Acrylates; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Cough; Double-Blind Method; Drug Administration Schedule; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Imidazoles; Incidence; Male; Middle Aged; Probability; Quality of Life; Reference Values; Risk Assessment; Severity of Illness Index; Thiophenes; Treatment Outcome

Eprosartan is a new nonphenyl angiotensin II receptor blocker, which has been approved for the treatment of hypertension. Although the drug has a relatively short plasma half-life of 5 to 9 h, clinical studies have suggested that its antihypertensive effect persists for 24 h.. We assessed both the changes in 24-h and trough blood pressure (BP) (last 4 h of the ambulatory BP while the patient was awake) of eprosartan at doses of 600 and 1,200 mg once daily in a randomized, double-blind, placebo-controlled trial. Ambulatory BP was monitored at placebo baseline and after 8 weeks of double-blind therapy.. Two hundred patients randomized in the study with 177 patients completing the trial. The 24-h change in BP from baseline was 0.2/0.1 +/- 1.4/1.0 mm Hg, -7.9/ -5.4 +/- 1.0 mm Hg (P < .0001), and -7.4/-5.0 +/- 0.9 mm Hg (P < .0001) in the placebo, 600-mg eprosartan, and 1,200-mg eprosartan groups, respectively. Changes in trough ambulatory BP showed significant reductions of -6.3/-4.1 +/- 1.6/1.1 mm Hg and -7.7/-5.5 +/- 1.5/1.0 mm Hg for 600 mg of eprosartan and 1,200 mg of eprosartan, respectively.. These data demonstrate that eprosartan at doses of 600 or 1200 mg significantly reduced BP throughout an entire 24-h dosing period. There were no differences between the 600- and 1,200-mg dose; thus, 600 mg once daily should be the only dose used in the treatment of hypertension with eprosartan.

Topics: Acrylates; Adult; Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Double-Blind Method; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Prospective Studies; Thiophenes

To compare the efficacy and safety of eprosartan and enalapril to lower systolic blood pressure in elderly patients with essential hypertension.. 334 patients >65 years with sitting systolic blood pressure (sitSBP) > or = 160 mmHg and diastolic blood pressure (sitDBP) 90-114 mmHg were randomized to 12 weeks of double-blind treatment with eprosartan, 600-800 mg once daily (o.d.) or enalapril (5-20 mg o.d.), with flexible dose titration to lower systolic blood pressure below 140 mmHg. The primary outcome measure was change in sitSBP at endpoint.. Least-squares mean changes from baseline in sitSBP were -18.0 and -17.4 mmHg in the eprosartan and enalapril groups, respectively (difference eprosartan-enalapril -0.6, 95% confidence interval, CI, -4.1 to 3.0, p = 0.76). The corresponding figures for sitDBP were -9.4 and -9.6 mmHg (difference eprosartan-enalapril 0.2, 95% CI -1.7 to 2.0, p = 0.84). Normalization and response rates were also similar in the two groups. Adverse events were recorded in 61 (35.7%) patients on eprosartan (one with dry cough) and 83 (50.9%) patients on enalapril (10 with dry cough).. Eprosartan and enalapril were equally effective in reducing sitSBP and sitDBP in elderly patients with predominantly systolic hypertension. Eprosartan was better tolerated and, in particular, lacked the propensity of enalapril to cause dry cough.

Topics: Acrylates; Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Imidazoles; Male; Maximum Tolerated Dose; Therapeutic Equivalency; Thiophenes; Treatment Outcome

The primary objective of this double-blind, parallel-group, placebo-controlled, multicentre study was to compare the antihypertensive efficacy of one versus two daily doses of eprosartan, a novel nonbiphenyl, nontetrazole angiotensin II receptor antagonist, in 243 patients with mild to moderate hypertension (sitting diastolic blood pressure > or = 95 to < or = 114 mmHg).. The patients were randomized to titrated doses of eprosartan at 400-800 mg once a day, eprosartan at 200-400 mg twice a day, or placebo, with the incremental dose titrated over a 9-week period. Patients reaching target blood pressure (sitting diastolic blood pressure of < or = 90 mmHg) continued the fixed-dose treatment for 4 weeks. The primary efficacy measure was the mean change in trough sitting diastolic blood pressure from baseline to the study endpoint, determined on an intent-to-treat basis.. By the end of the study, eprosartan had significantly reduced mean trough sitting systolic and diastolic blood pressure relative to baseline and to placebo. The mean +/- SD change from baseline in diastolic pressure was -9 +/- 8.4 mmHg for the single daily dose, -9 +/- 8.5 mmHg for two doses a day and -4 +/- 8.1 mmHg for placebo (P < 0.0001 versus placebo for both eprosartan regimens). Similarly, both eprosartan regimens significantly reduced mean trough standing systolic and diastolic blood pressure. At the end of the study, the response rate in the single daily dose group (46.8%) was significantly higher than in the placebo group (25.6%). There were no significant differences between the treatment groups in the number of patients whose blood pressure responded to treatment; 41.7% of those taking eprosartan once a day and 44.4% of those taking eprosartan twice a day, and who responded to treatment, were maintained on their original starting doses. The total daily dose required to achieve target blood pressure was comparable, whether eprosartan was administered once or twice a day. Both eprosartan regimens were well tolerated and the incidence of adverse events with eprosartan was similar to that of placebo.. These results demonstrate that there was no significant difference in antihypertensive efficacy or tolerance between eprosartan taken in one or in two daily doses. Both dosing regimens provided significant and clinically meaningful reductions in blood pressure that were superior to placebo. Eprosartan in a single daily dose was shown to be an effective antihypertensive agent. Because of the good adverse-effect profile and the simplicity of a single daily dose, eprosartan has the potential to improve patient compliance.

Topics: Acrylates; Aged; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hypertension; Imidazoles; Male; Middle Aged; Prospective Studies; Thiophenes; Treatment Outcome

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. This paper reports the results of 27 asymptomatic patients who were recruited into a single centre substudy of the multicentre trial and randomised to receive either eprosartan (200-300 mg b.i.d.) or enalapril (5-20 mg o.d.). Blood pressure (BP) reduction, left ventricular (LV) mass regression and change in coronary flow reserve (CFR) after 6 months' treatment with either eprosartan or enalapril were compared. At the end of the study, eprosartan and enalapril were found to have caused similar reductions in BP. There was an increase in CFR in the eprosartan group to 1.6 +/- 0.3 and a decrease in CFR in the enalapril group to 1.3 +/- 0.3. Neither value was significantly different from baseline although the difference between the two groups was significant (p = 0.05). By study endpoint, there was a significant reduction in LV mass in the enalapril group (p = 0.05), but not the eprosartan (p = ns) group. Further investigation of the effects of angiotensin receptor blockers on CFR and LV mass regression appear warranted.

Topics: Acrylates; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Coronary Circulation; Double-Blind Method; Enalapril; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Imidazoles; Thiophenes

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. The secondary objective was to compare antihypertensive efficacy between treatments. This paper reports the results of a prespecified subgroup analysis performed in the patients under and over 65 years of age recruited into the study. Eprosartan was titrated from 200 mg b.i.d. to 300 mg b.i.d. and enalapril from 5 mg o.d. to 20 mg o.d. over 12 weeks. Hydrochlorothiazide (HCTZ) 12.5-25 mg o.d. could be added where required to the treatment for the final 6 weeks of the titration phase if SitDBP > or = 90 mmHg. Patients received the maximum titrated dosage during the maintenance phase. In the study overall, the incidence of cough at monotherapy endpoint was significantly higher in the enalapril-treated group than in the eprosartan-treated group (p = 0.018). Similar mean changes in blood pressure from baseline were evident with each treatment. The elderly subpopulation mirrored the response of the study as a whole. Both treatments lowered BP with a further reduction evident following the addition of HCTZ at week 18. In conclusion, eprosartan is effective and safe in elderly hypertensive patients. The combination of eprosartan and HCTZ is also well tolerated and provided additional efficacy in those patients not responding to eprosartan alone. Compared with eprosartan enalapril was associated with an increased risk of cough. These results suggest that, irrespective of age, patients may be less likely to discontinue treatment with eprosartan than with an ACE inhibitor.

Topics: Acrylates; Age Factors; Aged; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Consumer Product Safety; Cough; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Imidazoles; Male; Thiophenes

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. The secondary objective was to compare antihypertensive efficacy between treatments. This paper reports the effects seen on the safety profile, plasma renin activity, aldosterone and angiotensin II (A-II) in each treatment group. Eprosartan was titrated from 200 mg b.i.d. to 300 mg b.i.d. and enalapril from 5 mg o.d. to 20 mg o.d. over 12 weeks. Hydrochlorothiazide (HCTZ) 12.5-25 mg o.d. could be added where required to the treatment for the final six weeks of the titration phase if SitDBP > or = 90 mmHg. Patients received the maximum titrated dosage during the maintenance phase. In the study overall, similar mean changes in blood pressure from baseline were evident with each treatment. Measurement of mean plasma neurohormone levels showed significant increases in renin activity in both groups and statistically significant A-II elevations in the eprosartan group (p < 0.05). Neither eprosartan nor enalapril significantly altered serum lipid profiles or electrolyte levels. Most adverse experiences reported throughout the study were mild or moderate in both treatment groups. Fewer patients receiving eprosartan (4.9%) than enalapril (9.1%) discontinued treatment because of adverse experiences. In conclusion, the results of this study show that eprosartan is well tolerated. Both eprosartan and enalapril significantly increased plasma renin activity while plasma A-II was elevated in the eprosartan group.

Topics: Acrylates; Adult; Aged; Aged, 80 and over; Aldosterone; Analysis of Variance; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Consumer Product Safety; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Renin; Thiophenes

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. The secondary objective was to compare antihypertensive efficacy between treatments. This paper reports the results of a prespecified subgroup analysis performed in the 40 black patients recruited into the study. Eprosartan was titrated from 200 mg b.i.d. to 300 mg b.i.d. and enalapril from 5 mg o.d. to 20 mg o.d. over 12 weeks. Hydrochlorothiazide (HCTZ) 12.5-25 mg o.d. could be added where required to the treatment for the final six weeks of the titration phase if SitDBP > or = 90 mmHg. Patients received the maximum titrated dosage during the maintenance phase. In the study overall, the incidence of cough at monotherapy endpoint was significantly higher in the enalapril-treated group than in the eprosartan-treated group (p = 0.018). This trend was reflected in the black subgroup but the numbers were too small to confirm significance. At study endpoint the mean change in SitDBP was -10.5 +/- 1.9 mmHg and -9.6 +/- 2.4 mmHg for eprosartan-treated and enalapril-treated patients, respectively. The mean change in SitSBP for eprosartan-treated black patients was -18.8 +/- 3.5 mmHg and for enalapril-treated patients was -10.5 +/- 3.7 mmHg. The black subpopulation mirrored the response of the study as a whole. Both treatments lowered BP with a further reduction evident following the addition of HCTZ at week 18. In conclusion, eprosartan is effective and appears to be safe in black hypertensive patients. The combination of eprosartan and HCTZ was also well tolerated and provided additional efficacy in those patients not responding to eprosartan alone. The incidence of treatment-associated cough in the black subgroup was low, but there were no apparent differences between treatment groups.

Topics: Acrylates; Adult; Aged; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Black People; Blood Pressure; Consumer Product Safety; Cough; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Thiophenes

A multicenter, randomized, double-masked, placebo-controlled trial was conducted to assess the efficacy of once-daily eprosartan, a nonbiphenyl, nontetrazole angiotensin II-receptor antagonist, in 243 patients with mild-to-moderate systemic hypertension (sitting diastolic blood pressure [SitDBP], 95-114 mm Hg). After a 3-to 5-week single-masked placebo run-in period to obtain baseline values, patients were randomly allocated to receive 600 mg eprosartan once daily or placebo for 8 weeks. All clinic blood pressure measurements were made 24 hours +/-90 minutes after dosing. Eprosartan produced statistically and clinically significant reductions in SitDBP(-7.5+/-0.8 mm Hg) and sitting systolic blood pressure (SitSBP) (-6.0+/-1.3 mm Hg) compared with placebo (SitDBP -1.9+/-0.7 mm Hg; SitSBP 0.8+/-1.2 mm Hg). The 95% confidence intervals for the difference from placebo were -8.1 to 4.1 for SitDBP and -11.0 to -4.0 for SitSBP (both, P<0.0001). The proportion of patients responding (SitDBP was <90 mm Hg or had decreased by > or =10 mm Hg from baseline at study end point) to eprosartan was significantly higher than the proportion of those responding to placebo (42% vs. 21%, respectively; P = 0.0003). Similar results were obtained in a subgroup analysis comparing patients aged <65 years with those aged > or =65 years. The total number of adverse events was similar in the eprosartan and placebo groups. Eprosartan 600 mg once daily was both well tolerated and effective, providing significant blood pressure reduction 24 hours after dosing in patients with mild-to-moderate systemic hypertension, regardless of age.

Topics: Acrylates; Age Factors; Aged; Angiotensin II; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Drug Administration Schedule; Female; Heart Rate; Humans; Hypertension; Imidazoles; Male; Middle Aged; Placebos; Prospective Studies; Sex Factors; Thiophenes

The effects of a new angiotensin receptor antagonist, eprosartan (200 or 300 mg b.i.d.) and enalapril (5-20 mg u.i.d.) on cough and blood pressure were compared in a 26-week, double-blind, randomised, parallel-group, multicentre, international study involving 528 patients with hypertension. Uptitration of doses was based on clinic blood pressure measurements during the first 12 weeks, after which hydrochlorothiazide (12.5-25 mg/day) could be added. The frequency and intensity of cough was assessed by a standardised questionnaire administered at each clinic visit. The primary end-point was the incidence of persistent, dry cough not due to upper respiratory infection; change in sitting diastolic blood pressure and overall incidence of cough were secondary end-points. During the first 12 weeks of double-blind therapy, enalapril treatment was associated with a 3.45-fold higher risk of definite cough (14/261 vs 4/259, P = 0.018). Overall cough incidence (from spontaneous reports from patients, or investigator's observation) was also more frequent with enalapril, as compared to eprosartan. Both agents reduced blood pressure significantly compared to baseline, although the eprosartan-treated group had a slightly higher response rate (defined as sitting diastolic blood pressure <90 mm Hg, or at least a 10 mm Hg reduction from baseline), both at end of titration (70.3% vs 62.6%, P < 0.05) and after 26 weeks (81.7% vs 73.5%, P= 0.018). These data suggest that, in unselected hypertensive patients, eprosartan is associated with less cough and a somewhat higher responder rate than enalapril.

Topics: Acrylates; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Cough; Diuretics; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Incidence; Male; Middle Aged; Risk Factors; Single-Blind Method; Sodium Chloride Symporter Inhibitors; Surveys and Questionnaires; Thiophenes; Treatment Outcome

The influence of angiotensin II AT-1 receptor antagonists on uric acid metabolism, and the potential differences among them with regard to this effect, remains to be precisely established. This study was designed to compare the effects of losartan and eprosartan on uric acid metabolism in patients with mild to moderate essential hypertension.. Randomized, double-blind, parallel-group study in hypertensive patients.. Outpatient clinic.. Following a 2- to 3-week single-blind placebo run-in period, 60 patients with sitting diastolic blood pressure > or = 95 and < or = 114 mmHg were randomized. Fifty-eight patients completed the study.. Patients were randomized to receive losartan 50 mg or eprosartan 600 mg once daily for 4 weeks.. The primary endpoint was the change in the ratio of urinary uric acid/creatinine in the period 0-4 h of a 24 h urine collection after 4 weeks of treatment. Secondary endpoints included 24 h urinary uric acid excretion, as well as serum urate and anti-hypertensive efficacy.. Mean urinary uric acid/creatinine changes from baseline were 0.14 (day 1) and 0.11 (week 4) for losartan and -0.04 for eprosartan (at both day 1 and week 4; P < 0.01 between groups at both time-points). The mean increase in 24 h urinary uric acid excretion with losartan was 0.7 mmol/24 h (25% increase from baseline) at both day 1 and week 4. No significant difference was observed in the change of serum urate levels versus baseline between both treatment groups after 4 weeks (- 23.4 and - 19.5 micromol/l for losartan and eprosartan, respectively). Patients with hyperuricaemia in both treatment groups showed similar modifications of uric acid metabolism compared with non-hyperuricaemic subjects. Blood pressure control (sitting diastolic blood pressure < 90 mmHg or < 100 mmHg with a decrease of at least 10 mmHg from baseline) was achieved in 22 patients (73%) with eprosartan and in 16 (53%) with losartan.. Losartan increased uric acid excretion in hypertensive patients, whilst eprosartan did not Neither AT-1 receptor antagonist substantially modified serum urate concentrations.

Topics: Acrylates; Administration, Oral; Aged; Antihypertensive Agents; Double-Blind Method; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Thiophenes; Uric Acid

The efficacy of eprosartan, a highly selective, orally-active non-biphenyl, non-tetrazole, type 1 angiotensin II (AT1) receptor antagonist, was compared with that of the angiotensin-converting enzyme (ACE) inhibitor, enalapril, with the addition of hydrochlorothiazide (HCTZ) when necessary in patients with severe hypertension (sitting diastolic blood pressure [sitDBP] > or = 115 mmHg and < or = 125 mmHg). Patients (n = 118) were randomized into an 8-week, double-blind titration phase and were started on oral eprosartan 400 mg total daily dose, given b.i.d., or oral enalapril 10 mg total daily dose, given o.d. The dose of eprosartan was increased to 600 and 800 mg daily, given b.i.d., and that of enalapril to 20 and 40 mg daily, given o.d., at weeks 2 and 4 if sitDBP was > or = 90 mmHg. If blood pressure remained uncontrolled on maximum doses of eprosartan or enalapril at week 6, HCTZ 25 mg o.d. was added to the treatment regimen. Patients whose blood pressure was deemed medically acceptable by the investigator at week 8 entered a 2-week maintenance phase on the final dose used in the titration phase. The primary efficacy measure was the difference between treatments of the mean reduction from baseline in sitDBP at the end of the study. Eprosartan and enalapril caused a similar reduction in sitDBP at study endpoint. The mean change in sitDBP at the end of the study for the eprosartan group was -20.1 mmHg vs -16.2 mmHg for the enalapril group. However, eprosartan produced significantly greater decreases in both sitting and standing systolic blood pressure (sitSBP and staSBP, respectively) than enalapril. The mean decrease in sitSBP was 29.1 mmHg for eprosartan compared with 21.1 mmHg for enalapril (p = 0.025). The mean reduction in staSBP was 27.8 mmHg for eprosartan compared with 20.0 mmHg for enalapril (p = 0.032). At the end of the study, the response rate (sitDBP < 90 mmHg or decreased from baseline by at least 15 mmHg) was 69.5% in the eprosartan group and 54.2% in the enalapril group. The proportion of patients in each treatment group who required addition of HCTZ was similar. Eprosartan was well tolerated; the overall incidence of adverse events was comparable to that in the enalapril group. These results demonstrate that in patients with severe hypertension, eprosartan is well tolerated and may be more effective than enalapril in reducing systolic blood pressure.

Topics: Acrylates; Administration, Oral; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Enalapril; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Thiophenes

The effects of antihypertensive agents, including angiotensin II receptor antagonists, on urine uric acid excretion may have important clinical consequences. Therefore, the effects of single and repeated doses of eprosartan on uric acid excretion were evaluated in 57 male patients with mild-to-moderate essential hypertension in a double-blind, randomized, placebo-controlled, repeated dose, dose-rising, two-period, period-balanced, crossover study conducted in two parts. In part 1 (n = 33), the effects of eprosartan dose regimens of 50 mg, 100 mg, and 350 mg once daily and 150 mg every 12 hours on uric acid excretion were assessed. In part 2 (n = 24), the effects of eprosartan dose regimens of 600 mg, 800 mg, and 1,200 mg once daily on uric acid excretion were assessed. Eprosartan was well tolerated. There were no appreciable changes from predose values in fractional excretion of uric acid (FEua), urine uric acid excretion, urine uric acid to creatinine (Uua/Ucr) ratios, or serum uric acid concentrations after single or repeated doses of eprosartan. Mean Uua/Ucr ratios for eprosartan doses of 50 mg, 100 mg, or 350 mg daily or 150 mg every 12 hours were comparable to those for placebo. Mean FEua values and Uua/Ucr ratios for eprosartan doses of 600 mg, 800 mg, or 1,200 mg daily also were comparable to those for placebo. Single and repeated oral doses of eprosartan ranging from 50 mg to 1,200 mg daily had no effect on serum uric acid concentrations or urine uric acid excretion in patients with mild-to-moderate essential hypertension.

Topics: Acrylates; Adult; Angiotensin Receptor Antagonists; Antihypertensive Agents; Creatinine; Cross-Over Studies; Double-Blind Method; Humans; Hypertension; Imidazoles; Male; Middle Aged; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Thiophenes; Uric Acid

Hypertension, a form of cardiovascular diseases, is considered a major risk factor associated with deaths in type 2 diabetes patients. The current medication systems for treating such chronic coexisting diseases are limited and challenging due to the difficulties in overcoming the side effects from complex therapeutic and treatment regimen. The objective of the present study is to design and optimize pioglitazone (PIO) and eprosartan mesylate (EM)-loaded nano-transferosomes (NTs) using Design-Expert software, aiming its transdermal delivery as a novel combination therapy for concomitant treatment of hypertensive diabetic patients. The developed formulations were characterized for various parameters, including in-vitro skin permeation, skin irritation, in-vivo antidiabetic, and antihypertensive activities. NTs were prepared using PIO and EM as the two model drugs and optimized using Box-Behnken design by considering phospholipid (X1), surfactant (X2), ratio of solvents (X3), and sonication time (X4), as independent variables, each at three levels. Entrapment efficiency (Y1 and Y2) and flux (Y3 and Y4) of PIO and EM, respectively, were selected as dependent variables. Among all the prepared formulations, one optimized formulation was chosen by the point prediction method and evaluated for drug-polymer compatibility, particle size, and surface charge analysis, followed by skin permeation and pharmacodynamic studies. The optimized nano-transferosomal gel (ONTF) showed all responses which confirm with the values predicted by the design. Pharmacodynamic studies showed improved and prolonged management of diabetes and hypertension in Wistar rats after the ONTF was applied, compared to oral and drug-loaded NT formulations. Results of the current study suggest that the development of such combinational delivery system can result in a rational therapeutic regimen for effective treatment of concomitant disease conditions of diabetic hypertensive patients.

Topics: Acrylates; Animals; Diabetes Mellitus, Type 2; Drug Carriers; Drug Delivery Systems; Humans; Hypertension; Imidazoles; Liposomes; Mesylates; Particle Size; Pioglitazone; Rats; Rats, Wistar; Thiophenes

We identified 55 504 uncomplicated, treatment-naïve hypertensive patients who started angiotensin II receptor blockers (ARBs) in 2012 from national claims data. The proportion of patients remaining on any hypertension treatment at 12 months and the adherence rate were similar between the losartan cohort (66.82% and 68.25%) and the nonlosartan ARB cohort (67.48% and 69.01%). After adjusting for confounding factors, there was no difference in persistence (aHR 0.98, 95% confidence interval (CI) 0.95-1.01) on hypertension treatment between losartan and nonlosartan ARB cohort. Post hoc analysis showed that patients initially prescribed eprosartan, irbesartan (both, aHR 1.33), and telmisartan (aHR 1.11) were more likely to discontinue the initial drug, whereas valsartan initiators (aHR 0.96) were less likely compared with losartan initiators.

Topics: Acrylates; Adult; Aged; Angiotensin Receptor Antagonists; Biphenyl Compounds; Cohort Studies; Female; Humans; Hypertension; Imidazoles; Irbesartan; Losartan; Male; Medication Adherence; Middle Aged; Outcome Assessment, Health Care; Republic of Korea; Retrospective Studies; Risk Factors; Tetrazoles; Thiophenes; Valsartan

Angiotensin II (Ang II) is thought to play an important role in the development of hypertension. Nevertheless, knowledge on the angiotensin II type-1-receptors (AT1Rs) in the hypertensive kidney and the influence of sodium intake and renin-angiotensin system activity on intrarenal AT1R blockade is scarce. To improve our understanding of renal AT1Rs in hypertensive patients, we studied the effects of acute, local administration of AT1R-blocker eprosartan in kidneys of patients with essential hypertension (off medication).. In 73 hypertensive patients who were scheduled for diagnostic renal angiography, we measured renal blood flow (Xenon washout method) before and during intrarenal infusion of two incremental doses of eprosartan (3 and 10 μg/kg/min for 15 min per dose). We hypothesized that the vasodilatory effects of eprosartan would be enhanced by low sodium intake and would be reduced during Ang II co-infusion. Therefore, we allocated the patients to either a high or a low sodium diet and coinfused Ang II (1 ng/kg/min) in a subgroup.. Eprosartan infusion resulted in intrarenal vasodilation in all groups. No differences in the magnitude of this effect were found between the groups. No correlation was found between 24-h urinary sodium excretion (a proxy for dietary sodium intake) and the effect of eprosartan.. Eprosartan-induced vasodilation is not influenced by sodium intake and/or co-infusion of Ang II. These rather unexpected findings could be explained by differences between circulating and tissue Ang II levels, variations in AT1R expression, and/or stimulation of other vasodilatory pathways.

Topics: Acrylates; Adult; Aged; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Essential Hypertension; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Receptor, Angiotensin, Type 1; Renal Artery; Renal Circulation; Renin-Angiotensin System; Sodium; Sodium, Dietary; Thiophenes; Vasodilation

The study of emotional and personality characteristics of patients with hypertension in the workplace (HW) and comparative assessment of the effectiveness of antihypertensive therapy in these patients.. The study included 170 patients c hypertensive disease stage II, 1-2-th degree, aged 32-52 years, including 85 patients with and 85 patients without WAH, and 82 healthy subjects matched for age and sex. To carry out simulation of the situation of emotional intensity (level of claims assessment process - UE) and a modified version of the test Rosenzweig. Patients with WAH were randomized into 2 groups: patients of group 1 received bisoprolol, 2nd group -eprosartan. If target blood pressure (BP) in 2 weeks, all patients were added indapamide retard. At baseline and after 16 weeks of treatment was carried out daily monitoring of blood pressure and the working day.. When modeling a situation of emotional intensity in patients with WAP become, compared with patients without a healthy and WAH, revealed (1) marked increase in systolic blood pressure - 16.1, 4.1 and 3.0 mmHg, respectively (p <0,001 ), (2) the dominance of motivation "avoid failure" (UP underestimated in 34.1% of cases, unformed UP - in 21.2% of cases, healthy - 14.6% and 3.7% of cases, cootvetstvenno, p<0,001 in patients without WAH - 20% and 11.8%, respectively, p<0,05). Patients with WAP become different from normal was significantly (p<0.05) the number of the selected blshim emotionally meaningful situations (9.7 and 7.8, respectively) and emotional descriptors (11 and 7, respectively). Patients with WAH differ significantly (p<0,05) more frequent than in healthy, the use of ineffective strategies of emotion regulation in an emotionally meaningful situations: the suppression of the expression of emotions (38.3 and 20.3%, respectively), rumination and disasterization (19 and 11.8%, respectively) and more rare - high performance: sequential actualization of new meanings (25.7 and 31.7%, respectively) and the strategy of interactive subject-subject transformations (12.6 and 25.2%, respectively). After 16 weeks of treatment showed a significant (p<0,001) reduction of blood pressure in the 1st and 2nd groups. The number of patients achieving target blood pressure, at 2, 4 and 6 weeks, respectively, was as follows: 14 in the bisoprolol group and 93 (100%), in the eprosartan group - 0, 52 (100%). Both groups showed significant (p <0,001) reduction in mean daytime and nighttime blood pressure in the weekdays and weekends. In the group of bisoprolol showed a significant (p <0,01) higher average daily decrease in systolic blood pressure in the working day, compared with eprosartan group (26.2 and 19.3 mm Hg, respectively).. Patients with WAP become emotionally meaningful situations frequently resorted to repression of emotions, choose the inefficient strategies of emotion regulation, they noted the expressed reaction of BP in response to the emotional burden. Antihypertensive therapy based on bisoprolol, is highly effective and has advantages over circuit-based therapy with eprosartan.

Topics: Acrylates; Adult; Antihypertensive Agents; Bisoprolol; Blood Pressure; Blood Pressure Determination; Emotions; Female; Humans; Hypertension; Imidazoles; Indapamide; Male; Middle Aged; Random Allocation; Stress, Psychological; Thiophenes; Treatment Outcome

The Observational Study on Cognitive function And systolic blood pressure Reduction (OSCAR) was designed to evaluate the impact of eprosartan-based therapy on cognitive function in a cohort of 25,745 hypertensive subjects followed for six months.. In this supplementary analysis, we studied the relationship between eprosartan-based therapy and cognitive function (assessed using the Mini-Mental State Examination (MMSE)) after 12-month follow-up of 3600 patients (the long-term follow-up on-treatment population).. Reduction in blood pressure was sustained over 12 months, with mean systolic blood pressure/diastolic blood pressure 130.9/79 mmHg at one year, compared with 164.3/92.8 mmHg at baseline (p<0.001). The overall mean MMSE score at completion of 12-month follow-up was significantly increased from baseline (27.8 ± 2.7 vs. 26.3 ± 3.5; p<0.001). The increase in MMSE score was observed when the population was stratified by age (p<0.001) and in a subgroup of patients with cerebrovascular disease at baseline (n=290) (p<0.001, 12 months vs. baseline).. In this cohort of patients, use of eprosartan-based treatment for one year was associated with sustained reduction in blood pressure and stabilization or improvement of MMSE scores. These data are supportive of a role for blood pressure control in the prevention or delay of cognitive decline.

Topics: Acrylates; Aged; Aged, 80 and over; Blood Pressure; Cognition; Demography; Diastole; Female; Follow-Up Studies; Humans; Hypertension; Imidazoles; Male; Middle Aged; Neuropsychological Tests; Systole; Thiophenes

An 83-year-old woman with hypertension received the angiotensin-II receptor type 1 blocker (ARB) eprosartan for more than 10 years. Six months ago, the dosage of the drug was doubled, and the patient reported a sudden onset of diarrhea. Duodenal biopsies showed a celiac disease-like pathology with flattened mucosa and an increase of intraepithelial lymphocytes and eosinophils, but serology of celiac disease remained negative. Celiac disease-like changes have been previously reported to be associated with other ARBs. This is the first case following eprosartan medication. In celiac-disease-like pathology of the small bowel with negative serology, drug-induced changes, for example due to ARBs, should be excluded.

Topics: Acrylates; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Celiac Disease; Female; Humans; Hypertension; Imidazoles; Thiophenes

The Canadian Hypertension Education Program (CHEP) has identified blood pressure (BP) control as a key target for an overall reduction in cardiovascular disease risk. The POWER survey (Physicians' Observational Work on Patient Education According to their Vascular Risk) used Framingham methodology to investigate the impact of an angiotensin-receptor-blocker-based regimen on arterial BP and total coronary heart disease (CHD) risk in a subset of patients recruited in Canada.. 309 Canadian practices screened for patients with either newly diagnosed or uncontrolled mild/moderate hypertension (sitting systolic blood pressure [SBP] >140 mmHg with diastolic blood pressure [DBP] <110 mmHg). Treatment comprised eprosartan 600 mg/day with add-on antihypertensive therapy after 1 month if required. The primary efficacy variable was change in SBP at 6 months; the secondary variable was the absolute change in the Framingham 10-year CHD risk score.. 1,385 patients were identified, of whom 1,114 were included in the intention-to-treat (ITT) cohort. Thirty-eight point four percent of ITT patients were managed with monotherapy at 6 months, versus 35.2% and 13.7% with two-drug or multiple-drug therapy, respectively. SBP in the ITT cohort declined 22.4 (standard deviation [SD] 14.8) mmHg and DBP declined 10.5 (SD 10.3) mmHg during that time. The absolute mean Framingham score declined 2.1 (SD 3.1) points with significant age and sex variation (P<0.001) and differences between the various Framingham methods used.. Primary care physicians were able to use a strategy of BP lowering and CHD risk assessment to achieve significant reductions in BP and Framingham-assessed CHD risk. The effect size estimate of the different Framingham methods varied noticeably; reasons for those differences warrant further investigation.

Topics: Acrylates; Aged; Angiotensin II Type 2 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Canada; Coronary Disease; Drug Therapy, Combination; Female; Health Care Surveys; Humans; Hypertension; Imidazoles; Male; Middle Aged; Primary Health Care; Risk Assessment; Risk Factors; Thiophenes; Time Factors; Treatment Outcome

This article describes the design and methodology of the POWER study (Physicians' Observational Work on Patient Education According to their Vascular Risk). POWER is an open-label multinational postmarketing study of the angiotensin II-receptor blocker eprosartan. The Systemic Coronary Risk Evaluation (SCORE) model has been used to estimate total cardiovascular risk and changes in total cardiovascular risk status during treatment for patients recruited in all countries other than Canada. Framingham Heart Study equations have been used to estimate risk in the Canadian contingent of POWER. Observations from POWER will provide insights into how clinicians try to achieve blood pressure goals within the framework of total cardiovascular risk management and how they integrate their treatment of blood pressure with other interventions. Experience during the POWER study may also help to affirm the utility, practicability and perhaps limitations of the SCORE system for estimating total cardiovascular risk and identify ways to improve the acceptance and implementation of risk estimation methods in cardiovascular primary prevention.

Topics: Acrylates; Antihypertensive Agents; Blood Pressure; Blood Pressure Determination; Canada; Cardiovascular Diseases; Humans; Hypertension; Imidazoles; Primary Health Care; Product Surveillance, Postmarketing; Research Design; Risk Factors; Thiophenes

The Observational Study on Cognitive Function and SBP Reduction (OSCAR) provided opportunities to examine the influence of eprosartan on trends in cognitive performance in a large population of patients with difficult-to-treat hypertension (DTTH). A total of 4649 patients diagnosed retrospectively with DTTH, defined as systolic/diastolic blood pressure (SBP/DBP) ≥140/90 mm Hg despite use of at least 3 antihypertensive drugs during the month preceding the baseline visit comprised the intention-to-treat (ITT) cohort. The patients were given eprosartan-based antihypertension therapy (EBT; 600 mg/d). Blood pressure and cognitive function parameters included significant (P<.001) differences for DTTH vs non-DTTH patients such as older age, body mass index, SBP and pulse pressure (PP), and lower Mini-Mental State Examination (MMSE) score. After EBT for 6 months, SBP/DBP in DTTH was 138.8±12.2/81.9±7.4 (ΔSBP-26±15.7; ΔDBP-11.4±9.8); PP was 57.0±10.8 (ΔPP-14.5±13.8) (all P<.001 vs baseline and non-DTTH group). A total of 2576 patients (87.4%) responded to EBT (ie, SBP <140 mm Hg and/or ΔSBP ≥15 mm Hg, or DBP <90 mm Hg and/or ΔDBP ≥10 mm Hg); 1426 DTTH patients (48.4%) achieved normalized SBP/DBP (ie, SBP <140 mm Hg and DBP <90 mm Hg). ΔPP in DTTH-isolated systolic hypertension (ISH) was -18.0±13.3 mm Hg (P=.003 vs DTTH-systolic-diastolic hypertension). End-of-EBT mean MMSE was 27.5±3.0 (P<.001 vs baseline). Blood pressure responses after EBT coincided with stabilization/improvement of MMSE in this retrospective investigation in DTTH patients. The average improvement in MMSE in DTTH patients was similar to that in non-DTTH patients. EBT effects on PP may be relevant to the evolution of MMSE in DTTH-ISH patients.

Topics: Acrylates; Aged; Angiotensin II Type 2 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Cognition; Female; Humans; Hypertension; Imidazoles; Intention to Treat Analysis; Male; Middle Aged; Retrospective Studies; Thiophenes

Effects of melaxen on the circadian chronostructure of AP and pulse rate was studied in 57 assembly-line shift workers with arterial hypertension of whom 23 were given melaxen with teveten and 34 teveten alone for 3 weeks. Introduction of melaxen in therapy of AH reduced AP and normalized disturbed circadian hemodynamics. Moreover, combined treatment eliminated sleep disturbances not infrequent in such patients.

Topics: Acrylates; Adult; Antihypertensive Agents; Circadian Clocks; Female; Humans; Hypertension; Imidazoles; Male; Melatonin; Middle Aged; Sleep Disorders, Circadian Rhythm; Thiophenes; Work Schedule Tolerance

Estimation of total cardiovascular risk is useful for developing preventive strategies for individual patients. The POWER (Physicians' Observational Work on Patient Education According to their Vascular Risk) survey, a 6-month, open-label, multinational, post-marketing observational evaluation of eprosartan, an angiotensin II receptor blocker, was undertaken to assess the efficacy and safety of eprosartan-based therapy in the treatment of high arterial blood pressure in a large population recruited from 16 countries with varying degrees of baseline cardiovascular risk, and the effect of eprosartan-based therapy on total cardiovascular risk, as represented by the SCORE (Systematic Coronary Risk Assessment) or Framingham risk equations.. Participating physicians recruited > 29,000 hypertensive patients whom they considered to be candidates (according to specified criteria) for treatment with eprosartan 600 mg/day, with other drugs added at the discretion of the physician.. During treatment, systolic blood pressure decreased by 25.8 ± 14.4 mmHg to 134.6 ± 11.4 mmHg (P < 0.001), mean diastolic blood pressure fell by 12.6 ± 9.5 mmHg to 81.1 ± 7.6 mmHg, and pulse pressure fell by 13.2 ± 13.5 mmHg to 53.6 ± 11.4 mmHg (both P < 0.01). Calculated total cardiovascular risk declined in parallel with the reduction in blood pressure.. The POWER study has demonstrated, in a large and nonselected population, the feasibility and practicability of reducing total cardiovascular risk through systematic management of high blood pressure.

Topics: Acrylates; Adolescent; Adult; Aged; Aged, 80 and over; Angiotensin II Type 2 Receptor Blockers; Blood Pressure; Cardiovascular Diseases; Chi-Square Distribution; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Product Surveillance, Postmarketing; Risk Factors; Statistics, Nonparametric; Systole; Thiophenes; Treatment Outcome

ATP-binding cassette (ABC)-transporters, such as P-glycoprotein (P-gp/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs) and breast cancer resistance protein (BCRP/ABCG2) transport numerous drugs thus regulating their absorption, distribution and excretion. Angiotensin receptor type 1 blockers (ARBs), used to treat hypertension and heart failure, are commonly administered in combination therapy. However, their interaction potential is not well studied and their effect on ABC-transporters remains elusive. The study therefore aimed to elucidate the effect of various ARBs (telmisartan, candesartan, candesartan-cilexetil, irbesartan, losartan, olmesartan, olmesartan-medoxomil, eprosartan) on ABC-transporter activity in vitro. P-gp inhibition was assessed by calcein assay, BCRP inhibition by pheophorbide A efflux assay, and MRP2 inhibition by a MRP2 PREDIVEZ Kit. Induction of P-gp, BCRP and MRP2 was assessed by real time reverse transcriptase polymerase chain reaction and for P-gp also in a functional assay. Telmisartan was identified as one of the most potent inhibitors of P-gp currently known (IC(50)=0.38+/-0.2 microM for murine P-gp) and it also inhibited human BCRP (IC(50)=16.9+/-8.1 microM) and human MRP2 (IC(50)=25.4+/-0.6 microM). Moreover, the prodrug candesartan-cilexetil, but not candesartan itself, significantly inhibited P-gp and BCRP activity. None of the compounds tested induced mRNA transcription of P-gp or BCRP but eprosartan and olmesartan induced MRP2 mRNA expression. In conclusion, telmisartan substantially differed from other ARBs with respect to its potential to inhibit ABC-transporters relevant for drug pharmacokinetics and tissue defense. These findings may explain the known interaction of telmisartan with digoxin and suggest that it may modulate the bioavailability of drugs whose absorption is restricted by P-gp and possibly also by BCRP or MRP2.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP-Binding Cassette Transporters; Benzimidazoles; Biological Transport; Biphenyl Compounds; Digoxin; Fluoresceins; Humans; Hypertension; Imidazoles; Irbesartan; Losartan; Membrane Transport Proteins; Mice; Multidrug Resistance-Associated Protein 2; Olmesartan Medoxomil; Tetrazoles; Thiophenes

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

The work was designed to study effect of melaxen on circadian chronostructure of arterial pressure and pulse rate in subjects with arterial hypertension occupied in assembly line production. A total of 57 patients were examined of whom 23 received teveten together with melaxen and 34 were treated with teveten alone for 3 weeks. Inclusion of melaxen in combined therapy of hypertension reduced arterial pressure and normalized disturbed circadian hemodynamics. It is concluded that combined therapy effectively eliminates sleep disorders frequent in this group of patients.

Topics: Acrylates; Administration, Oral; Adult; Antihypertensive Agents; Blood Pressure; Central Nervous System Depressants; Circadian Rhythm; Drug Therapy, Combination; Follow-Up Studies; Humans; Hypertension; Imidazoles; Industry; Melatonin; Middle Aged; Occupational Diseases; Occupational Exposure; Thiophenes; Treatment Outcome

The aim of this study was to compare the effectiveness and safety of eprosartan in reducing blood pressure in a group of diabetic patients and a group of non-diabetic patients in a primary care setting.. The ESTEPP (Efficacy and Safety of Treatment with Eprosartan on Pulse Pressure) study was open, prospective, multi-centered, and observational. It compared the results obtained from diabetic (n=114, age 65.0+/-10.7 years, 46.4% men and 53.6% women) and non-diabetic patients (n=435, age 62.5+/-11.4 years, 45.8% men and 54.2% women). All patients had mild to moderate hypertension (VI JNC) and were treated with eprosartan (600 mg) once daily. They had four follow-up visits in 16 weeks. At each visit, blood pressure (using a semiautomatic OMRON 705CP device), adverse effects, and treatment compliance were checked.. Blood pressure decreased significantly (P<0.0001) in both diabetic and non-diabetic patients: SBP (25.9 mmHg vs. 26 mmHg), DBP (12.5 mmHg vs. 13.2 mmHg), MAP (16.9 mmHg vs. 17.5 mmHg), and pulse pressure (13.4 mmHg vs. 12.8 mmHg). Pulse pressure/MAP ratio showed a significant reduction in diabetics (baseline: 64+/-15%; final: 61+/-12%) and non-diabetics (baseline: 61+/-14%; final: 58+/-11%). The adverse effect rate was 7% in diabetic patients and 2.8% in non-diabetics. Treatment compliance did not differ between the groups (diabetics 98.0%, non-diabetics 92.2%).. Eprosartan seems to be effective in reducing SBP, DBP, and pulse pressure in hypertensive subjects and to the same extent in both diabetic and non-diabetic patients.

Topics: Acrylates; Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Determination; Diabetes Complications; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Prospective Studies; Thiophenes; Time Factors; Treatment Outcome

The influence of angiotensin II blocker in thrombocytes aggregative capacity in patients with arterial hypertension and metabolic syndrome was assessed. 32 patients were treated with eprosartan during 16 weeks. Dynamics of lipid peroxidation in plasma and thrombocytes, liquid part of blood and platelets antioxidant immunity, thrombocytes aggregative capacity were assessed. The results were processed using Student's test. The use of eprosartan in patients with arterial hypertension and metabolic syndrome has positive influence on peroxidation syndrome and optimizes thrombocytes aggregation.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Female; Follow-Up Studies; Humans; Hypertension; Imidazoles; Male; Metabolic Syndrome; Middle Aged; Platelet Aggregation; Thiophenes; Treatment Outcome

Data from several recent clinical trials have suggested a beneficial effect of antihypertensive medications on preservation of cognitive function. Eprosartan, an angiotensin type-1 receptor antagonist (ARA) with dual action on both pre- and postsynaptic angiotensin type 1 receptors, may be effective in the control of SBP and the prevention of cognitive decline. The OSCAR (Observational Study on Cognitive function And SBP Reduction) study is an international longitudinal observational study with a duration of 6 months intended to examine the impact of the ARA eprosartan on cognitive function (assessed using the Mini-Mental State Examination [MMSE]) and control of systolic blood pressure (SBP) in a large international population of hypertensive patients managed in a standard primary care setting. A total of 100,000 hypertensive patients, aged >or=50 years and with SBP of >140 mmHg will be recruited by more than 20 000 primary care physicians in 27 countries. These patients will receive eprosartan 600 mg once a day for 6 months. The MMSE, a globally validated cognitive screening test, will be performed at baseline, and after 6 months of treatment. After the first month of monotherapy, eprosartan treatment may, at the absolute discretion of individual investigators, be supplemented with other antihypertensive medications for the remainder of the study. The primary outcome indices are the mean relative change in MMSE score and the absolute change from baseline in SBP in the study population as a whole and in subsets of patients according to various factors among them: ethnicity, comorbidities (i.e. target organ damage, diabetes), baseline cognitive level and baseline blood pressure level. The secondary objectives are to identify factors influencing SBP and MMSE changes. The OSCAR trial is the first international observational study focusing on MMSE in a wide international cohort of hypertensive patients. The results are expected in 2007.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Cognition; Cognition Disorders; Female; Humans; Hypertension; Imidazoles; Longitudinal Studies; Male; Middle Aged; Multicenter Studies as Topic; Neuropsychological Tests; Observation; Patient Selection; Receptor, Angiotensin, Type 1; Research Design; Thiophenes

In hypertensive patients, the activated renin-angiotensin system induces a prothrombotic state resulting from imbalance between coagulation and fibrinolysis. Although blood pressure cannot be regulated in therapy-resistant hypertensive patients, they may still be responsive to medication that attenuates the renin-angiotensin system.. our objective was to study possible attenuating properties of angiotensin II type 1 receptor blockers (AT1RBs) on the prothrombotic state in therapy-resistant hypertensive patients, focusing on parameters of fibrinolysis and coagulation.. Fourteen therapy-resistant hypertensive patients received AT1RB eprosartan infusion (45 and 150 microg kg(-1)) (study group), and 33 therapy-resistant hypertensive patients received saline (0.9%) infusion (control group) prior to renal angiography. Baseline values of parameters of coagulation and fibrinolysis were set at 1.00, and relative changes were calculated.. Plasminogen activator inhibitor type 1 (PAI-1) antigen showed non-significant decreases in both the study group (arterial 1.00-0.45, venous 1.00-0.42) and control group (arterial 1.00-0.84, venous 1.00-0.88). PAI-1 activity significantly decreased in the study group (arterial 1.00-0.72, venous 1.00-0.71) and control group (arterial 1.00-0.83, venous 1.00-0.94). In the study group, tissue-type plasminogen activator (t-PA) antigen decreased significantly (arterial 1.00-0.62, venous 1.00-0.67), whereas t-PA activity significantly increased (arterial 1.00-6.15, venous 1.00-2.66). In the control group, t-PA antigen remained unchanged. No changes were observed in blood pressure during and after infusion of eprosartan.. Therapy-resistant hypertensive patients show beneficial changes in fibrinolytic activity after infusion of a non-pressor dose of AT1RB.

Topics: Acrylates; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Blood Coagulation; Case-Control Studies; Drug Resistance; Endothelial Cells; Female; Fibrinolysis; Humans; Hypertension; Imidazoles; Male; Middle Aged; Thiophenes

Moderate elevations in blood pressure translate to significant increases in cardiovascular and cerebro vascular risk. Beneficially, this relationship allows small decreases in blood pressure to be associated with risk reduction. Both the renin-angiotensin system and the sympathetic nervous system are involved in hypertension, hence targeting these systems is likely to be of benefit in the treatment of hypertension. Angiotensin II type 1 receptor blockers (ARBs) are used for controlling blood pressure and treating heart failure in a broad range of patients, including those with diabetes and the elderly. Not only have ARBs shown good efficacy and tolerability, they also appear to have a protective effect that goes beyond that expected from the reduction of blood pressure. The ARB eprosartan is a nonbiphenyl nontetrazole angiotensin II type 1 receptor (AT1) antagonist, which acts to decrease total peripheral resistance. Eprosartan acts at vascular AT1 receptors (postsynaptically) and at presynaptic AT1 receptors, where it inhibits noradrenaline release. In clinical studies, eprosartan has been shown to significantly reduce cardiovascular and cerebrovascular events, whilst avoiding the persistent cough that commonly occurs with the use of angiotensin-converting enzyme inhibitors. Eprosartan can also be differentiated from other ARBs due to its noradrenergic effects, which other ARBs used at therapeutic doses do not possess. Eprosartan, therefore, represents a useful therapeutic option in the management of patients with hypertension, including those with a history of stroke or with co-morbid type 2 diabetes mellitus.

Topics: Acrylates; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Cardiovascular Diseases; Cerebrovascular Disorders; Humans; Hypertension; Imidazoles; Middle Aged; Risk; Thiophenes

The subjects of the study were 30 patients with type II diabetes mellitus and mild or moderate arterial hypertension. Clinical-and-hemodinamic organoprotective effects of eprosartan, a new angiotensin II blocker, was evaluated in these patients within 16 weeks. The study found a good hypotensive effect of monotherapy with eprosartan in a mean therapeutic dose of 600 mg/day--the target blood pressure levels were achieved in 63.3% of the patients. Fasting insulin level and insulin resistance decreased, which improved hydrocarbonate and lipid exchange parameters. Eprosartan was significantly effective as an organoprotective agent: the patients displayed improvement of eye ground vessel condition, decrease of microalbuminuria, improvement of cardiodynamic parameters i.e. decrease of the thickness of left ventricular (LV) back wall and intravenricular septum, as well as reduction of myocardial mass index. 70% of the patients demonstrated improvement of LV diastolic function.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Data Interpretation, Statistical; Diabetes Mellitus, Type 2; Diastole; Female; Humans; Hypertension; Imidazoles; Insulin; Insulin Resistance; Lipid Metabolism; Male; Middle Aged; Receptor, Angiotensin, Type 1; Thiophenes; Time Factors; Treatment Outcome; Ventricular Function, Left

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

To assess the influence of work stress and initial blood pressure on the prognosis of hypertension.. In a prospective, controlled, multicentre, observational study, ambulatory 24-hour blood pressure measurements (ABPM) of employees from different work places were recorded at the work place on working days. Recurrent ABPM were performed for up to 5 years on 3448 subjects (mean age 44.6 years) who gave consent for follow-up. Subjects with hypertension were told to consult their family doctor so that they could receive antihypertensive treatment (the angiotensin receptor blocker eprosartan, an ACE-inhibitor or a beta-blocker were recommended for initial treatment). Subjects were classified as being in mental strain (stress-positive [stress+]/ stress-negative [stress-]), using standardized questionnaires.. Only 1242 (36.0%) of the 3448 employees (69.% males) were normotensives. Only 166 (7.5%) of the 2206 hypertensives had normal ABPMs (<135/85 mmHg) and received antihypertensive treatment at the time of inclusion into the trial. During follow-up 57.8% of patients were treated with eprosartan or ACE-inhibitors, 34.6% with beta-blockers. By the time of the final visit 80.5% of hypertensives had achieved improvement of systolic and/or diastolic blood pressures (29.1% normotensive). Patients with hypertensive ABPM at baseline had more cardiovascular events than normotensives (normotensives 3.0%; grade 1 7.8%, grade 2-3 9.8%). Hypertensive ABPMs at the last follow up or an increase in blood pressure grade were associated with higher event rates than normotensives (stable normotensives 1.8% events vs. stable hypertensives 7.9%, vs. worsening or grade 2-3: 9.1%) More hypertensives were classified as stress+ than normotensives. Persons classified as stress- (or changing to stress-) had fewer events (6.2%) than those regarded as stress+ or changing to stress+ (7.1%). Persons regarded as stable stress- had lower mean blood pressures than those who were stable stress+. Change to another stress group was associated with an increase or decrease of mean blood pressure.. Many employed people are hypertensive at work and are not treated adequately. ABPM control and antihypertensive treatment based on eprosartan, ACE-inhibitors or beta-blockers resulted in a significant increase in the number of patients with lower blood-pressure levels and a reduction in cardiovascular events. Patients under mental strain were more likely to be hypertensive. Mental strain was associated with changes in blood pressure.

Topics: Acrylates; Adrenergic beta-Antagonists; Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Female; Follow-Up Studies; Humans; Hypertension; Imidazoles; Male; Middle Aged; Occupational Diseases; Prognosis; Prospective Studies; Stress, Physiological; Thiophenes; Workplace

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

The purpose of this investigation was to determine whether angiotensin II receptor (AII1R) antagonism interferes with cardiac monocyte chemoattractant protein-1 (MCP-1) expression in hypertrophic cardiomyopathy and failure.. We studied the effects of the AII1R antagonist eprosartan on MCP-1 expression, and on the recruitment of macrophages into the myocardium in a model of cardiac hypertrophy and morbidity/mortality.. Stroke-prone spontaneously hypertensive rats fed a high-salt, high-fat diet (SFD) developed heart failure characterized by left ventricular (LV) hypertrophy/pathology and hypocontractility. These rats received either normal diet, SFD, or SFD with the daily administration of 30 mg/kg eprosartan for 28 weeks. LV function and wall thickness was assessed by echocardiography, MCP-1 expression was measured by TaqMan real-time polymerase chain reaction, enzyme-linked immunosorbent assay and immunohistochemistry, and macrophage infiltration into the LV was determined by microscopy.. Eprosartan reduced the rate of morbidity/mortality (P = 0.001), LV MCP-1 mRNA (P < 0.05) and protein expression (P < 0.01), and LV macrophage infiltration (P < 0.01), while preserving ventricular function (P < 0.05). Eprosartan also produced a moderate (16%; P < 0.05) decrease in blood pressure.. These data demonstrate that AII1R antagonism in an animal model of hypertensive heart disease reduces MCP-1 expression in the myocardium that results in reduced macrophage recruitment. These effects parallel the preservation of LV systolic function and the reduction in cardiac remodeling/disease progression and reduced morbidity/mortality. Suppression of MCP-1 expression might explain in part the beneficial effects of AII1R antagonism in this model.

Topics: Acrylates; Angiotensin II; Animals; Antihypertensive Agents; Chemokine CCL2; Down-Regulation; Hypertension; Hypertrophy, Left Ventricular; Imidazoles; Immunohistochemistry; Macrophages; Myocardial Contraction; Myocardium; Rats; Rats, Inbred SHR; RNA, Messenger; Thiophenes; Ultrasonography; Vasculitis

Diabetes mellitus seems to induce an special difficulty to control the high blood pressure. This effect is more severe on the SBP. Previous reports suggest that a new angiotensin receptor blocker, eprosartan, might have a higher efficacy to reduce SBP. It has been evaluated the BP decrease obtained with eprosartan in a group of diabetics patients compared to non diabetic patients.. 81 patients were recruited of whom 65 have ended follow-up. 34 patients were diabetics (mean age 66.7+/-10.7 years, 15 men and 19 women) and 31 were non diabetics control patients (mean age 61.8+/-12,8 years, 13 men and 18 women). All patients were treated with (600 mg) once daily. The doses was ingested in the morning. They were made three follow up visits (1, 3 and 6 mo after the first visit).. SBP was significantly decreased both in diabetics (baseline 170.9+/-12.0, final 139.1+/-13.0 mmHg, p < 0.001) and in non diabetics group (baseline 169.9+/-18.0, final 142.0+/-13.3 mmHg, p < 0.001). DBP was also reduced in both groups (diabetics: baseline 92.9+/-9.7, final 78.4+/-8.5 mmHg, p < 0.001; non diabetics: baseline 95.6+/-7.9, final 79.1+/-7.4 mmHg, p < 0.001). Differences between the groups were not significant in any visit. Final BP reduction reached was -31.7/-14.6 mmHg in diabetics vs -27,6/-16,5 mmHg in non diabetics patients (difference is not significant) Pulse pressure changes were not different between the two groups (diabetics, 17.8+/-14.5, vs non diabetics, 11.1+/-13.2 mmHg). Two diabetic patients need a second drug to achieve BP goal and no one in non diabetic group. No adverse effects were reported.. Eprosartan seems to be an effective drug to reduce SBP, DBP and pulse pressure with the same effectiveness in diabetics and non diabetic patients.

Topics: Acrylates; Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Diabetes Complications; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Thiophenes

Angiotensin II (Ang II) is a potent vasoconstrictor and induces inflammation and end-organ injury through its activation of the proinflammatory transcription factor, nuclear factor-kappaB (NF-kappaB). Heat shock (HS) treatment with subsequent expression of heat shock proteins (Hsps) is an effective strategy for tissue protection against oxidative injuries. Recently, HS and Hsps have been shown to interact with NF-kappaB in tissue injury. In this study, we investigated whether HS could protect against Ang II-induced hypertension and inflammation by inhibiting NF-kappaB. Sprague-Dawley rats were divided into control and HS groups. Control and 24-hour post-heat shocked rats were treated with Ang II. At days 1, 3, 5, 7, 11, and 14 after Ang II administration, systolic blood pressures were measured by tail-cuff plethysmography, and aorta tissues were collected. Aorta NF-kappaB deoxyribonucleic acid-binding activity was measured by electrophoretic mobility shift assay, and NF-kappaB p65 subunit, Hsp70, Hsp27, and interleukin-6 (IL-6) expressions were measured by Western analysis. HS treatment significantly decreased Ang II-induced hypertension. The activation of NF-kappaB in aorta by Ang II was suppressed by HS treatment. The elevated expression of IL-6 induced by Ang II treatment was also decreased by HS treatment. Although Ang II treatment induced an increase in Hsp70 and Hsp27, HS treatment induced a greater elevation of Hsp70 and Hsp27 expression. HS treatment protects against Ang II-induced hypertension and inflammation. This protection may relate to the interaction of Hsps and the NF-kappaB pathway.

Topics: Acrylates; Angiotensin II; Animals; Antihypertensive Agents; Aorta; Blood Pressure; Blotting, Western; Electrophoretic Mobility Shift Assay; Heat-Shock Response; Hot Temperature; HSP70 Heat-Shock Proteins; Hydralazine; Hypertension; Imidazoles; Inflammation; Interleukin-6; Intracellular Signaling Peptides and Proteins; Male; NF-kappa B; NF-kappa B p50 Subunit; Norepinephrine; Protein Serine-Threonine Kinases; Rats; Rats, Sprague-Dawley; Thiophenes; Transcription Factor RelA

Topics: Acrylates; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Circadian Rhythm; Data Interpretation, Statistical; Exercise Test; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Thiophenes; Time Factors

Systolic blood pressure (SBP) and pulse pressure (PP) are accurate predictors of cardiovascular events in the elderly population. In these patients, isolated systolic hypertension (ISH) is an important risk factor for cardiovascular morbidity and mortality.. A multicentre, observational, prospective study, evaluated the effects of 16 weeks of eprosartan treatment on PP and other blood pressure (BP) parameters. Data from a subgroup of patients from this study, who had ISH, are presented here.. Eprosartan monotherapy reduced SBP, PP and mean blood pressure (MBP) over the duration of treatment, whereas diastolic blood pressure (DBP) remained unchanged. There was no difference in the reductions of these parameters between eprosartan monotherapy and combination therapy. In addition, a high proportion of patients responded to eprosartan therapy. The response to eprosartan therapy was significantly influenced by family history of early cardiovascular disease, but not by gender, body mass index (BMI), raised low-density lipoprotein (LDL)-cholesterol, smoking, left ventricular hypertrophy, or previous history of cardiovascular disease. Patients aged > or =70 years had a decreased reduction in DBP and MBP components. Eprosartan therapy was well tolerated, with only 1% of patients reporting an adverse event.. Eprosartan is an effective and well-tolerated antihypertensive therapy for elderly patients with ISH.

Topics: Acrylates; Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Determination; Body Mass Index; Cardiovascular Diseases; Cholesterol, LDL; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Prospective Studies; Risk Factors; Sex Factors; Thiophenes; Time Factors

Topics: Acrylates; Age Factors; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Canada; Drug Utilization; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Prognosis; Risk Assessment; Systole; Thiophenes; Treatment Outcome

Pulse pressure is an important cardiovascular risk factor, particularly in the elderly and in patients with isolated systolic hypertension. The differential impact of antihypertensive agents on pulse pressure is not known.. To assess the antihypertensive effect of treatment with the angiotensin II receptor blocker eprosartan on pulse pressure, and the factors influencing this effect.. The present study was an observational study of 4067 patients (55% women, mean age 67 years) with essential hypertension, newly diagnosed or unresponsive to current treatment, in which 3133 patients received 12 weeks of treatment with eprosartan 600 mg/day (87% monotherapy) in primary care centres. Blood pressure was measured using a validated oscillometric device (Omron 705CP, Omron Healthcare Inc, USA).. Eprosartan significantly reduced pulse pressure at 12 weeks (13.5 mmHg, P<0.001). The reductions in systolic, diastolic and mean blood pressures were also statistically significant (26.0 mmHg, 12.6 mmHg and 17.1 mmHg, respectively). After correcting the pulse pressure for hypertension severity (pulse pressure/mean blood pressure ratio), this index was reduced from 62% to 58% with eprosartan, suggesting a 4% reduction in the pulsatile component. This reduction was more pronounced in patients over 60 years of age, those with a higher index at baseline and those with hypertensive cardiovascular complications. Adverse drug reactions occurred in 1.5% of patients.. Eprosartan is an effective, well tolerated antihypertensive drug that reduces pulse pressure. This reduction is partially independent of the severity of high blood pressure, which may be important for both safety and target organ protection.

Topics: Acrylates; Administration, Oral; Aged; Aged, 80 and over; Analysis of Variance; Angiotensin II Type 1 Receptor Blockers; Blood Pressure; Blood Pressure Determination; Canada; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hypertension; Imidazoles; Male; Maximum Tolerated Dose; Middle Aged; Predictive Value of Tests; Probability; Prospective Studies; Risk Assessment; Severity of Illness Index; Thiophenes; Treatment Outcome

Antihypertensive agents are proven to reduce the cardiovascular risk of stroke, coronary heart disease and cardiac failure. The ideal antihypertensive agent should control all grades of hypertension and have a placebo-like side effect profile. Angiotensin II (AII) receptor antagonists are a relatively new class of antihypertensive agent that block AII Type 1 (AT(1)) receptors, and reduce the pressor effects of AII in the vasculature. By this mechanism, they induce similar pharmacological effects compared with angiotensin-converting enzyme (ACE) inhibitors, resulting in a lowering of blood pressure. However, AII receptor blockers differ from ACE inhibitors with respect to side effects, and induce less cough, a side effect which may be related to bradykinin or other mediators such as substance P. Within the class of AII blockers, eprosartan differs from other currently available agents in terms of chemical structure, as it is a non-biphenyl, non-tetrazole, non-peptide antagonist with a dual pharmacological mode of action. Eprosartan acts at vascular AT(1) receptors (postsynaptically) and at presynaptic AT(1) receptors, where it inhibits sympathetically stimulated noradrenaline release. Its lack of metabolism by cytochrome P450 enzymes confers a low potential for metabolic drug interactions and may be of importance when treating elderly patients and those on multiple drugs. In clinical trials, eprosartan has been demonstrated to be at least as effective in reducing blood pressure as the ACE inhibitor enalapril, and has significantly lower side effects. Eprosartan is safe, effective and well-tolerated in long-term treatment, either as a monotherapy or in combination with other antihypertensive drugs such as hydrochlorothiazide.

Topics: Acrylates; Administration, Oral; Angiotensin II Type 1 Receptor Blockers; Female; Humans; Hypertension; Imidazoles; Male; Receptor, Angiotensin, Type 1; Spain; Thiophenes

Topics: Acrylates; Angiotensin Receptor Antagonists; Antihypertensive Agents; Benzimidazoles; Benzoates; Biphenyl Compounds; Diuretics; Dizziness; Drug Combinations; Drug Interactions; Heart Failure; Humans; Hypertension; Imidazoles; Irbesartan; Kidney Diseases; Losartan; Olmesartan Medoxomil; Telmisartan; Tetrazoles; Thiophenes; Valine; Valsartan

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzothiadiazines; Diuretics; Drug Therapy, Combination; Humans; Hypertension; Imidazoles; Sodium Chloride Symporter Inhibitors; Thiophenes; Time Factors

Topics: Acrylates; Angiotensin I; Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Antihypertensive Agents; Benzimidazoles; Benzoates; Biphenyl Compounds; Clinical Trials as Topic; Germany; Humans; Hypertension; Imidazoles; Irbesartan; Losartan; Olmesartan Medoxomil; Placebos; Telmisartan; Tetrazoles; Therapeutic Equivalency; Thiophenes; Time Factors; Valine; Valsartan

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

Eprosartan (600-1200 mg/day) was given for 4 weeks to 28 patients aged 32-62 years with stage II-III hypertension (WHO, 1999). Left ventricular diastolic function and cerebral blood flow were assessed by echocardiography and ultrasound dopplerography. Treatment with eprosartan was associated with improvements of impaired left ventricular diastolic function, structural and functional state of the heart, venous outflow from cerebral vessels, and restoration of unpaired autoregulation of cerebral blood flow. All these phenomena could potentially lead to normalization of cerebral tissue perfusion and stabilization of cerebral blood flow.

Topics: Acrylates; Adult; Antihypertensive Agents; Carotid Artery, Internal; Cerebrovascular Circulation; Diastole; Echocardiography; Female; Follow-Up Studies; Homeostasis; Humans; Hypertension; Imidazoles; Male; Middle Aged; Models, Cardiovascular; Thiophenes; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Transcranial; Ventricular Function, Left; Vertebral Artery

Antagonists of the renin-angiotensin system, such as angiotensin type 1 (AT(1)) receptor inhibitors and angiotensin-converting enzyme inhibitors, are becoming increasingly popular agents in treating patients with systemic hypertension and minimizing organ damage. In the present study, we compared the effects of eprosartan, an AT(1) receptor inhibitor, with the diuretic hydrochlorothiazide in a group of newly diagnosed hypertensive patients with multiple risk factors for atherosclerosis. The subjects were monitored and tested at 0 and 4 weeks to determine their individual effects on vascular and inflammatory markers. Although blood pressure reduction was comparable between the 2 agents, there were notable differences in their effects on markers of inflammation and oxidation. We observed a 28% reduction in neutrophil superoxide anion generating capacity, a 34% reduction in soluble monocyte chemotactic protein-1, and a 35% reduction in soluble vascular cell adhesion molecule with eprosartan therapy (all p <0.05 from the start of therapy). In addition, eprosartan showed further benefit in its ability to increase low-density lipoprotein oxidation lag time, suggesting an increased resistance to oxidation and/or modification of low-density lipoprotein. Although hydrochlorothiazide was effective in blood pressure reduction, there were no significant changes in any of the above parameters after 4 weeks of treatment. These findings suggest that eprosartan, an AT(1) receptor inhibitor, effectively reduces systemic blood pressure and, compared with hydrochlorothiazide, suggests additional benefits in the vasculature by inhibiting mechanisms of inflammation and oxidation.

Topics: Acrylates; Adult; Angiotensin Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Chemokine CCL2; Dose-Response Relationship, Drug; Female; Gene Expression Regulation; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Inflammation; Lipoproteins, LDL; Male; Middle Aged; Muscle, Smooth, Vascular; Oxidation-Reduction; Receptors, Angiotensin; Renin-Angiotensin System; Thiophenes; Treatment Outcome; Vascular Cell Adhesion Molecule-1

To specify variable 24-h arterial hypertension (AH) stage II profile and to assess significance of pharmacological block of the end of the renin-angiotensin-aldosteron system for correction of the determined disorders.. The study was made of 46 men (mean age 42.8 +/- 3.28 years) with stage II AH and 25 normotensive controls (mean age 39.2 +/- 3.10 years). Depending on the magnitude of mean 24-h AP variability (APV), hypertensive patients were divided into two groups. Variability of systolic and/or diastolic AP (SAPV and DAPV, respectively) was considered high in at least 15.2 and/or 12.3 mm Hg variability, respectively, and normal at less values.. AP 24-h profile in men with AH stage II and high APV compared to patients with normal APV is characterized by higher frequency of AP rise and less frequency of its night fall. In patients with high APV the drug eprosartan (teveten) is more effective in correction of hypertension and night fall of AP.. Eprosartan has an adequate corrective activity in relation to absolute values of SAP and DAP in different hours. The highest hypotensive activity of the drug was seen in persons with initially high circadian AP variability within 24 hours.

Topics: Acrylates; Adult; Angiotensin II; Angiotensin Receptor Antagonists; Blood Pressure; Circadian Rhythm; Humans; Hypertension; Imidazoles; Male; Receptor, Angiotensin, Type 1; Thiophenes

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

Topics: Acrylates; Antihypertensive Agents; Circadian Rhythm; Humans; Hypertension; Imidazoles; Occupational Diseases; Stress, Psychological; Thiophenes; Workplace

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; Blood Pressure; Humans; Hypertension; Imidazoles; Thiophenes; Treatment Outcome

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

The role of ANG II on renal and cardiac gene expression of matrix proteins was studied in rats with progressive renal disease. Induction of renal failure by five-sixths nephrectomy of Sprague-Dawley rats resulted in hypertension (163 +/- 19 vs. control pressures of 108 +/- 6 mmHg), proteinuria (83 +/- 47 vs. 14 +/- 2 mg/day), and increased renal expression of fibronectin, thrombospondin, collagen I and III, transforming growth factor-beta (TGF-beta), and plasminogen activator inhibitor-1 (PAI-1) mRNA. Treatment with the ANG II receptor antagonist, eprosartan (60 mg. kg(-1).day(-1)), lowered blood pressure (95 +/- 5 mmHg) and proteinuria (19 +/- 8 mg/d) and abrogated the increased TGF-beta, fibronectin, thrombospondin, collagens I and III, and PAI-1 mRNA expression. An increase in left ventricular weight was observed in five-sixths nephrectomized rats (0.13 +/- 0.01 vs. 0.08 +/- 0.01 g/100 g body wt), a response that was inhibited by eprosartan treatment (0.10 +/- 0.01 g/100 g). Left ventricular expression of TGF-beta and fibronectin was also increased in rats with renal disease; however, the small decreases in expression observed in eprosartan-treated rats did not reach statistical significance. These data suggest that eprosartan may be beneficial in progressive renal disease and that the mechanism of action includes inhibition of cytokine production in addition to antihypertensive activity.

Topics: Acrylates; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Gene Expression Regulation; Hypertension; Imidazoles; Kidney Diseases; Male; Nephrectomy; Proteinuria; Rats; Rats, Sprague-Dawley; Thiophenes

Topics: Acrylates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Clinical Trials as Topic; Contraindications; Double-Blind Method; Half-Life; Humans; Hypertension; Imidazoles; Perindopril; Telmisartan; Thiophenes

Topics: Acrylates; Adult; Antihypertensive Agents; Black People; Enalapril; Female; Humans; Hypertension; Imidazoles; Losartan; Receptors, Angiotensin; Thiophenes

The antihypertensive activity of the nonpeptide angiotensin II receptor antagonist, SK&F 108566 (E)-alpha-[[2-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5- yl]methylene]-2-thiophene propanoic acid), was examined in rats and dogs. SK&F 108566 produced dose-dependent decreases in blood pressure in renin-dependent hypertensive rats. At 10 mg/kg intraduodenally, mean arterial blood pressure fell from between 150-160 mm Hg to approximately 124 mm Hg. A sustained infusion of SK&F 108566 at 25 micrograms/min intraduodenally normalized blood pressure during 3 days of infusion and for 18 h following cessation of the infusion. Evaluation of the systemic hemodynamic effects of SK&F 108566 in chronically instrumented renin-dependent hypertensive rats demonstrated that the antihypertensive effects of SK&F 108566 were accompanied by a significant increase in cardiac output with little change in stroke volume. In dogs made acutely hypertensive by an intravenous infusion of angiotensin I, SK&F 108566 resulted in dose-dependent decreases in blood pressure. The antihypertensive activity of SK&F 108566 at 10 mg/kg p.o. was maintained for between 13-15 h, a similar duration of action as observed with enalapril (1 mg/kg, p.o.). Administration of DuP 753 (losartan) intravenously caused a small and short-lived fall in blood pressure in the angiotensin I-infused hypertensive dog. However, the active metabolite of losartan, EXP 3174, resulted in a response of longer duration. In dogs made hypertensive by placement of an ameroid constrictor on the left renal artery, SK&F 108566 (10 mg/kg, p.o.) or enalapril (1 mg/kg, p.o.) resulted in antihypertensive responses of at least 12 h duration. The data indicate that SK&F 108566 is a long-acting antihypertensive agent in the rat and dog.

Topics: Acrylates; Angiotensin I; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Biphenyl Compounds; Dogs; Hemodynamics; Hypertension; Imidazoles; Losartan; Male; Rats; Rats, Inbred Strains; Tetrazoles; Thiophenes