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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antihypertensive treatment achieves its greatest benefit in the primary prevention of stroke. Primary prevention studies show 38% fewer strokes when systolic/diastolic values are reduced by 10-12/5-6 mmHg. Secondary stroke prevention has been less investigated, but restrokes seems to be reduced with antihypertensive treatment. Secondary prevention achieves 25-30% less strokes, if diastolic BP can be reduced by 3-4 mmHg. Today's guidelines for antihypertensive therapy in acute ischemic stroke suggest reducing BP values over 220 mmHg systolic (AHA) or 200/110 (German Hypertension Society). No data are available about antihypertensive treatment in acute stroke patients. No intervention trials have so far evaluated an immediate BP reduction on the clinical outcome of the patients neurological status (morbidity) or mortality rates in the acute stroke situation. However, some studies show an increase in mortality after a quick and rapid BP reduction in a short time interval. The ACCESS study was designed to evaluate the possible benefits of a careful and moderate, but immediate blood pressure reduction in patients with an acute stroke compared to a restrictive antihypertensive therapy. Candesartan cilexetil was selected as the antihypertensive drug for its slow onset of action and moderate BP reduction, as well as its very good tolerability. Experimental studies point at possible advantages in acute stroke. The study was designed as a prospective, randomized, double-blind, placebo-controlled, multicenter trial (500 patients). Inclusion criteria were an acute ischemic stroke with a motor paresis and severe hypertension. Primary endpoints were the patients morbidity (functional status measured with Rankin and Barthel index, degree of motor deficity by NIH scale) and mortality rates after three months. First results are presented.
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PMID:Hypertension and stroke--rationale behind the ACCESS trial. Acute Candesartan Cilexetil Evaluation in Stroke Survivors. 983 67

On the basis of results of long-term trials, to date, it is reasonable to conclude that blood pressure lowering, per se, rather than the identity of the antihypertensive regimen, is associated with reducing risk for stroke and coronary heart disease in patients with hypertension. Clinicians should identify drugs within each antihypertensive class that reduce blood pressure consistently over a 24-hour period and have a duration appropriate for once-daily administration. Candesartan cilexetil is an appropriate choice among angiotensin II receptor blockers (ARBs); it has a trough: peak ratio of 0.9-1.1, which fully justifies once-daily dosing. Once genuinely long-acting antihypertensive medications are used routinely, it will be possible to evaluate whether the different drug classes provide ancillary benefits beyond blood pressure lowering.
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PMID:Do pharmacologic differences among antihypertensive agents point to clinical benefits? 1058 91

Over the past 4 years, six angiotensin II receptor antagonists (ARBs) were approved for treating essential hypertension. They differ with respect to dosing, metabolism, elimination, clinical efficacy, and investigational applications. Candesartan cilexetil is the only prodrug among the agents. Losartan is distinguished from other ARBs by cytochrome P450 (CYP) 3A4- and CYP2C9-mediated biotransformation to its active metabolite EXP-3174. No ARB requires dosage adjustment for renal impairment, but the initial dose of losartan should be reduced 50% in hepatically impaired patients. None of the drugs is significantly cleared by hemodialysis. Completion of continuing trials will elucidate the drugs' role in treating heart failure, cerebral stroke, and myocardial infarction.
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PMID:Pharmacologic, pharmacokinetic, and therapeutic differences among angiotensin II receptor antagonists. 1067 91

Candesartan cilexetil is highly effective at lowering blood pressure, whilst maintaining placebo-like tolerability, in a wide range of patient groups. Although the benefit of lowering blood pressure in elderly patients with moderate hypertension has been demonstrated in several large-scale clinical trials, elderly patients with mild hypertension have rarely been studied. The high incidence of cardiovascular and cerebrovascular mortality and morbidity, including dementia, in the elderly means that control of blood pressure is particularly important in this patient group. A major new international clinical trial - SCOPE (Study on COgnition and Prognosis in the Elderly) - has therefore been initiated. This is a prospective, randomized, double-blind, parallel comparison of the effects of candesartan cilexetil, 8 or 16 mg once daily, and placebo in about 5000 patients who will be followed for a mean of 2.5 years. SCOPE is the first study designed to assess the effect of antihypertensive therapy in elderly patients (70-89 years of age) with mild hypertension (sitting systolic blood pressure of 160-179 mmHg and/or sitting diastolic blood pressure of 90-99 mmHg). The primary objective of the study is to determine the effect of candesartan cilexetil on major cardiovascular events (cardiovascular death, non-fatal stroke and myocardial infarction, and silent myocardial infarction), while an important secondary objective is to determine the effect of such treatment on the prevention of cognitive impairment. SCOPE should provide definitive evidence of the cardiovascular and cerebrovascular benefits of treating mildly hypertensive elderly patients with angiotensin II type 1 receptor blockers, which not only reduce blood pressure, but may also provide significant protection from the negative effects of angiotensin II on target organs.
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PMID:Reducing cardiovascular morbidity and mortality in the elderly. 1105 36

The nonpeptide AT(1) receptor antagonist candesartan is generated from the prodrug candesartan cilexetil during gastrointestinal absorption. In vitro studies have shown that candesartan acts as an insurmountable, tightly bound antagonist at the AT(1) receptor, producing a dose-dependent reduction in the maximal responses to angiotensin II (AII) and virtually an elimination of the AT(1) receptor-mediated effects of AII at high concentrations. The binding of candesartan to the AT(1) receptor is highly selective, and the drug dissociates slowly from the receptor. Candesartan cilexetil produces the expected changes in the parameters of the renin-angiotensin system. Plasma renin activity and plasma AII concentrations were increased and aldosterone levels decreased following drug application. As a consequence, stimulation of AT(2) receptor-mediated actions of AII, such as growth inhibition and vasodilation, may contribute to the overall effects of the AT(1) antagonist, since the AT(2) receptors are left unopposed by candesartan. The antihypertensive efficacy of candesartan cilexetil has been demonstrated in different animal models of hypertension including 2 kidney-1 clip and 1 kidney-1 clip hypertensive rats and spontaneously hypertensive rats (SHR). Candesartan cilexetil produced a slow onset, long-lasting antihypertensive action at a dose range of 0.1-10 mg/kg with no rebound effect upon drug withdrawal. A growing number of studies indicate that candesartan cilexetil can produce end organ protection in addition to lowering blood pressure. In preclinical studies, candesartan cilexetil caused prevention and regression of left ventricular hypertrophy and cardiac fibrosis, protected the heart against ischemia-reperfusion injury and reduced myocardial damage during myocarditis. In different animal models of renal dysfunction, candesartan cilexetil reduced proteinuria and albuminuria, inhibited histopathological renal changes and controlled the renal expression of TGF-beta1 and collagen types I and III. Finally, in stroke prone SHR, candesartan cilexetil markedly attenuated the incidence of stroke even at low doses, with minimal blood pressure lowering effects, and fully protected against stroke at higher doses.
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PMID:Candesartan cilexetil: development and preclinical studies. 1297 13

Hypertension is a major cardiovascular risk factor, but most patients remain asymptomatic for many years. Successful therapy not only needs to be effective, it also needs to be well tolerated. Angiotensin receptor blockers have emerged as a major therapeutic class because they meet both of these requirements. Numerous studies indicate that all approved angiotensin receptor blockers are highly selective for angiotensin-1 receptors, lower blood pressure as monotherapies, and work well in combination with other drugs - particularly diuretics. The side-effect profile of angiotensin receptor blockers is similar to that of placebo and they have not been associated with known side effects of angiotensin-converting enzyme inhibitors such as cough and angioneurotic edema. Candesartan cilexetil is an angiotensin receptor blocker with insurmountable binding properties to the angiotensin-1 receptor, long duration of action and improved efficacy. In patients with hypertension, candesartan monotherapy has been shown to be safe and effective. Comparative data have shown similar or better results to other monotherapies in blood-pressure control, and in combination with hydrochlorothiazide it has been shown to have additive or synergistic effects. More recent data demonstrate that candesartan cilexetil is useful in the treatment of patients with heart failure and may protect against diabetic nephropathy. Studies have also shown protection from stroke, particularly in patients with isolated systolic hypertension.
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PMID:Candesartan cilexetil in cardiovascular disease. 1550 Apr 28

Candesartan cilexetil is one of a number of drugs of the angiotensin II receptor blocker (ARB) class. Their principal mode of action involves competitive blockade of the angiotensin II type 1 receptor, thereby modulating the activity of the rennin-angiotensin-aldosterone system. Angiotensin II receptor blocker therapy has been proven to be well tolerated and effective in the management of hypertension, chronic heart failure with left ventricular dysfunction and the prevention and progression of diabetic renal disease. Candesartan is a highly potent, long-acting and selective angiotensin II type 1 receptor blocker. It was launched in 1998 for the treatment of hypertension. Its use has increased dramatically, with recently published data suggesting benefit in the treatment of stroke, heart failure, diabetic renal disease and most recently in preventing the development of or delaying the progression of diabetic retinopathy. In this article we review the literature on the use of ARB drugs in general before focusing on candesartan.
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PMID:Candesartan: widening indications for this angiotensin II receptor blocker? 1956 75

The advantages of blood pressure (BP) control on the risks of heart failure and stroke are well established. The renin-angiotensin system plays an important role in volume homeostasis and BP regulation and is a target for several groups of antihypertensive drugs. Angiotensin II receptor blockers represent a major class of antihypertensive compounds. Candesartan cilexetil is an angiotensin II type 1 (AT[1]) receptor antagonist (angiotensin receptor blocker [ARB]) that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system. Oral candesartan 8-32 mg once daily is recommended for the treatment of adult patients with hypertension. Clinical trials have demonstrated that candesartan cilexetil is an effective agent in reducing the risk of cardiovascular mortality, stroke, heart failure, arterial stiffness, renal failure, retinopathy, and migraine in different populations of adult patients including patients with coexisting type 2 diabetes, metabolic syndrome, or kidney impairment. Clinical evidence confirmed that candesartan cilexetil provides better antihypertensive efficacy than losartan and is at least as effective as telmisartan and valsartan. Candesartan cilexetil, one of the current market leaders in BP treatment, is a highly selective compound with high potency, a long duration of action, and a tolerability profile similar to placebo. The most important and recent data from clinical trials regarding candesartan cilexetil will be reviewed in this article.
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PMID:Differential clinical profile of candesartan compared to other angiotensin receptor blockers. 2224 49

Candesartan cilexetil is highly effective at lowering blood pressure, whilst maintaining placebo-like tolerability, in a wide range of patient groups. Although the benefit of lowering blood pressure in elderly patients with moderate hypertension has been demonstrated in several large-scale clinical trials, elderly patients with mild hypertension have rarely been studied. The high incidence of cardiovascular and cerebrovascular mortality and morbidity, including dementia, in the elderly means that control of blood pressure is particularly important in this patient group. A major new international clinical trial - SCOPE (Study on COgnition and Prognosis in the Elderly) - has therefore been initiated. This is a prospective, randomized, double-blind, parallel comparison of the effects of candesartan cilexetil, 8 or 16 mg once daily, and placebo in about 5000 patients who will be followed for a mean of 2.5 years. SCOPE is the first study designed to assess the effect of antihypertensive therapy in elderly patients (70-89 years of age) with mild hypertension (sitting systolic blood pressure of 160-179 mmHg and/or sitting diastolic blood pressure of 90-99 mmHg). The primary objective of the study is to determine the effect of candesartan cilexetil on major cardiovascular events (cardiovascular death, non-fatal stroke and myocardial infarction, and silent myocardial infarction), while an important secondary objective is to determine the effect of such treatment on the prevention of cognitive impairment. SCOPE should provide definitive evidence of the cardiovascular and cerebrovascular benefits of treating mildly hypertensive elderly patients with angiotensin II type 1 receptor blockers, which not only reduce blood pressure, but may also provide significant protection from the negative effects of angiotensin II on target organs.
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PMID:Reducing Cardiovascular Morbidity and Mortality in the Elderly. 2842 4