UMLS:C0038454 - FACTA Search

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

During the past years increasingly stricter criteria have been applied to the primary prevention of ischemic stroke. This applies especially to the treatment of asymptomatic carotid stenosis. An operation is indicated for a blockage of 60% and higher, including symptom-free patients under 75 years of age. At the moment, a final conclusion on the preferred operative procedure--thromboendarterectomy or stent implantation--cannot be made. For the secondary prevention of apoplexy, the highest relative risk reduction for vascular accidents using thrombocyte aggregation inhibitors was achieved with the combination ASA plus dipyridamole. Diuretics, calcium antagonists, ACE inhibitors and angiotensin receptor blockers (ARB) are equally suitable for the reduction of blood pressure after apoplectic insult. Moreover, the latter appear to have advantages for the prevention of a renewed apoplexy. The benefit of statins in the secondary prevention of apoplexy has been substantiated by the Heart Protection Study. Simvastatin has the best evidence for its effectiveness in patients without CHD; in contrast, atorvastatin has possibly more benefits for patients with clinically evident CHD. The direct thrombin inhibitor, ximelagatran, will be available as an alternative to the oral anticoagulant marcumar in the foreseeable future.
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PMID:[Apoplexy--current status of diagnostics and therapy]. 1596 73

The peptide hormone angiotensin (A)-II, the major effector peptide of the renin-angiotensin system (RAS), is well established to play a pivotal role in the systemic regulation of blood pressure, fluid, and electrolyte homeostasis. Recent biochemical and neurophysiologic studies have documented local intrinsic angiotensin-generating systems in organs and tissues such as the brain, retina, bone marrow, liver, and pancreas. The locally generated angiotensin peptides have multiple and novel actions including stimulating cell growth and anti-proliferative and/or antiapoptotic actions. In the mammalian brain, all components of the RAS are present including angiotensin receptor subtypes 1 (AT(1)) and 2 (AT(2)). A-II exerts most of its well defined physiologic and pathophysiologic actions, including those on the central and peripheral nervous system, through its AT(1) receptor subtype. While the AT(1) receptor is responsible for the classical effects of A-II, it has been found that the AT(2) receptor is linked to totally different signalling mechanisms and this has revealed hitherto unknown functions of A-II. AT(2) receptors are expressed at low density in many healthy adult tissues, but are upregulated in a variety of human diseases. This receptor not only contributes to stroke-related pathologic mechanisms (e.g. hypertension, atherothrombosis, and cardiac hypertrophy) but may also be involved in post-ischemic damage to the brain. It has been reported that the AT(2) receptor regulates several functions of nerve cells, e.g. ionic fluxes, cell differentiation, and neuronal tissue regeneration, and also modulates programmed cell death. In this article, we review the experimental evidence supporting the notion that blockade of brain AT(1) receptors can be beneficial with respect to stroke incidence and outcome. We further delineate how AT(2) receptors could be involved in neuronal regeneration following brain injury such as stroke or CNS trauma. The current review is focussed on some of the new functions arising from the locally formed A-II with particular attention to its emerging neuroprotective role in the brain.
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PMID:Neuroprotection with angiotensin receptor antagonists: a review of the evidence and potential mechanisms. 1598 7

Stroke is a major cause of death and disability and its incidence increases linearly with age and the level of systolic and diastolic blood pressure. Stroke, besides being a cause of long-term disability for the affected person, also imposes a significant burden on society and healthcare costs. Although good blood pressure control is very critical for stroke prevention, angiotensin receptor blockers (ARBs) may be superior to angiotensin-converting enzyme inhibitors (ACEIs) for the same degree of blood pressure control. This hypothesis has clinical and experimental support. ARBs prevent stroke incidence by blocking the angiotensin II (AII), AT1 receptors preventing brain ischaemia and allowing AII to stimulate the unoccupied AT2 receptors, which improve brain ischaemia. ACEIs, by reducing AII generation, are less effective in preventing stroke. This hypothesis provides evidence that AII plays an important role in the prevention of stroke. Certain ARBs like losartan, and telmisartan, irbesartan and candesartan possess additional properties which may play a role in stroke prevention, which is independent of AII. These include antiplatelet aggregating, hypouricemic, antidiabetic and atrial antifibrillatory effects. However, the most critical factor in stroke prevention is good blood pressure control irrespective of drug used.
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PMID:Possible pathophysiologic mechanisms supporting the superior stroke protection of angiotensin receptor blockers compared to angiotensin-converting enzyme inhibitors: clinical and experimental evidence. 1604 19

Diabetes mellitus, arterial hypertension, smoking are major stroke risk factors. The role of hypercholesterolemia in stroke has not been established yet. In patients with type 2 diabetes mellitus there is evidence that intensive glucose lowering therapy diminishes the risk of microvascular complications. In all patients with stroke or transient ischemic attack (TIA), blood pressure should be lowered irrespectively of the baseline level with either diuretics, angiotensin converting enzyme (ACE) inhibitors, beta-blockers, or calcium antagonists. The role of angiotensin II (AT2) receptor blockers has not been established so far. In general terms a global approach to management of patients with vascular risk factors should be developed. An extended follow-up of randomised trials on preventive therapy should be completed. Controlled trials comparing angiotensin receptor blockers with ACE inhibitors should be started. Further research may focus on the new lipid lowering agents, and on the comparison of single lipid lowering agent vs. combinations in stroke prevention. These efforts should help in finding the best vasoprotective strategy in stroke prevention.
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PMID:Antihypertensive and lipid lowering treatment in stroke prevention: current state and future. 1607 57

Angiotensin-converting enzyme inhibitors are widely-prescribed drugs for hypertension and are supported by clinical trials in which they reduce cardiovascular events. In the high-risk patients in the Heart Outcomes Prevention Evaluation, the Perindopril Protection Against Recurrent Stroke Study, and European Trial of Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease, ramipril and perindopril showed impressive benefits. One reason trandolapril did somewhat less well in the Prevention of Events With Angiotensin-Converting Enzyme Inhibition trial may be that its patients were very well treated with other effective modalities. In the Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial, lisinopril-treated patients had a slightly lower incidence of myocardial infarction, despite much poorer control of blood pressure, perhaps because a second-line diuretic was prohibited by protocol. Although angiotensin-converting enzyme inhibitors can cause cough and angioedema (more common among blacks), angiotensin receptor blockers are currently more expensive and have fewer outcome trials to support their use.
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PMID:Cardiovascular events in hypertension trials of Angiotensin-converting enzyme inhibitors. 1610 30

In the prevention of hypertensive complications, especially stroke and kidney disease, "lower is better" because for each decrease of 20 mm Hg systolic or 10 mm Hg diastolic pressure in the population, cardiovascular risk is halved. Ideally, the goal for each patient should be to reach the lowest blood pressure that is well tolerated, a value that may be well below the arbitrary threshold value of 140/90 mm Hg. For the majority of "uncomplicated hypertensives," the question of single-drug therapy is essentially moot, because more than one agent is almost always required to optimally control blood pressure. In individuals who already have heart or kidney disease, there are compelling indications for the use of drugs that block the renin-angiotensin system, but the large outcome studies that spawned these recommendations are themselves combination trials. Thus, in virtually all patients, more than one drug is indicated. The best combinations take advantage of long durations of action and complementary mechanisms of action of the component and are not only able to effectively lower blood pressure, but also to favorably affect the natural history of hypertensive complications. Regimens-including fixed-dose combination products-that combine a thiazide diuretic or calcium antagonist with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker are most efficient. In summary, why would an astute clinician (or informed patient) be satisfied with the relatively limited effects of any single class of antihypertensive agents when better overall protection is possible?
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PMID:Your drug, my drug, or our drugs: how aggressive should we be with antihypertensive therapy? 1610 31

In recent years, angiotensin receptor blockers (ARBs) have begun to represent a markedly larger percentage of the antihypertensive agents used in Japan. However, it remains uncertain whether ARBs are effective for protecting against hypertension-related organ damage in the general Japanese population. In the present report, we describe the results of a single blind, randomized, prospective study conducted in 1999-2002 and employing a total of 2,048 essential hypertensive subjects (sitting blood pressure 140-180/90-110 mmHg) aged 35-79 years. Subjects were randomly assigned to receive the ARB candesartan, 2 to 12 mg daily, or conventional antihypertensive drugs other than angiotensin converting enzyme inhibitors or ARBs. We used Cox regression analysis to compare the two regimens. The primary outcome was assessed by hospitalization due to stroke, myocardial infarction, and congestive heart failure. Blood pressure was reduced from 162.1/91.1 to 140.1/78.9 mmHg in the candesartan group and from 165.9/95.9 to 138.4/81.1 mmHg in the conventional therapy group. The main outcomes were as follows: there was a 39% reduction in hospitalization for stroke (5.8 vs. 9.4 cases: relative risk [RR]: 0.61; 95% confidence interval [CI]: 0.41-0.84; p<0.05) and a 57% reduction in hospitalization for myocardial infarction (RR: 0.44; CI: 0.21-0.84; p<0.05) with the candesartan-based treatment compared with the conventional treatment. In spite of a significant difference in the total incidence of both stroke and myocardial infarction, there was no significant reduction in the incidence of congestive heart failure (15% reduction: 4.3 vs. 5.0; RR: 0.85; CI: 0.57-1.26). Further analysis in stratifying the subjects with or without a past history of cardiovascular diseases including stroke and myocardial infarction revealed that candesartan reduced the incidence of stroke (61% reduction; RR: 0.39; CI: 0.15-0.43; p<0.01) and congestive heart failure (49% reduction; RR: 0.51; CI: 0.23-0.92; p<0.05) but not myocardial infarction (RR: 0.74; CI: 0.36-1.48; p=0.1) in hypertensive patients with a past history. However, conventional treatment was superior to candesartan-based treatment in reducing the incidence of stroke in the patients without a past history of cardiovascular diseases (66% reduction; RR: 0.34; CI: 0.16-0.69; p<0.05). This is the first demonstration that an ARB-based antihypertensive treatment was superior to the conventional treatment for reducing the risk of stroke and myocardial infarction in Japanese hypertensive patients, especially in the patients with a past history of cardiovascular diseases.
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PMID:Effects of candesartan on cardiovascular outcomes in Japanese hypertensive patients. 1613 60

We examined the efficacy of candesartan in reducing cardiovascular events in hypertensive patients with coexisting chronic kidney disease and cardiovascular diseases. This open-label, prospective study was conducted from 1999 to 2002, and 141 hypertensive subjects 60 to 75 years old with non-diabetic chronic renal insufficiency were enrolled. Before randomization of the patients, we examined their past medical history and found that 69 patients had been hospitalized due to myocardial infarction (MI) or stroke. Therefore, the patients were divided into 2 groups, one with previous histories of MI or stroke and the other with no previous history of Ml or stroke. The patients were randomized to receive either the angiotensin receptor blocker candesartan or conventional treatment. The mean duration of follow-up was 3.1 +/- 0.4 years. The primary outcome was a primary cardiovascular event (MI, stroke, or heart failure) verified by hospitalization. At the end of the study, in the patients with past history of cardiovascular diseases, blood pressure was reduced from 146.4 +/- 7.2/79.2 +/- 5.1 to 34.4 +/- 6.1/72.3 +/- 4.0 mmHg in the candesartan group and from 145.3 +/- 5.1/80.1 +/- 3.8 to 133.4 +/- 5.8/73.8 +/- 4.2 mmHg in the conventional treatment group. In the patients without past history of cardiovascular diseases, blood pressure was reduced from 143.2 +/- 4.3/78.3 +/- 4.8 to 133.8 +/- 5.3/ 73.1 +/- 3.8 mmHg in the candesartan group and from 143.9 +/- 6.8/78.1 +/- 4.2 to 132.6 +/- 5.4/74.5 +/- 4.4 mmHg in the conventional treatment group at the end of the study. There were no significant differences between the candesartan group and the conventional treatment group in the reduction of blood pressures. Among patients with a past history of cardiovascular disease, the serum creatinine concentration increased from 1.49 +/- 0.38 to 1.58 +/- 0.42 by candesartan treatment and from 1.50 +/- 0.32 to 1.89 +/- 0.37 by conventional treatment. On the other hand, in patients with no past history of cardiovascular disease, the serum creatinine concentration increased from 1.44 +/- 0.42 to 1.46 +/- 0.40 by candesartan treatment and from 1.46 +/- 0.44 to 1.51 +/- 0.38 by conventional treatment. Although, there was no significant difference in the incidence of cardiovascular events between the 2 groups with the candesartan-based and conventional-based antihypertensive treatment, in patients without cardiovascular events (12/36 vs. 7/34: these figures indicate events per total participated persons per 3 years; following figures are the same as this), treatment with candesartan reduced the incidence of cardiovascular events in the patients with past history of cardiovascular diseases (20/33 vs. 32/ 38). In particular, candesartan-based treatment reduced the incidence of congestive heart failure by 66.4% in these patients. In conclusion, this prospective, open-labeled randomized study suggests that 1) previous history of cardiovascular diseases is a major risk factor for cardiovascular events; and 2) candesartan is effective for reduction of cardiovascular events in hypertensive patients with coexisting chronic kidney disease and cardiovascular diseases, especially for prevention of congestive heart failure.
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PMID:An angiotensin receptor blocker reduces the risk of congestive heart failure in elderly hypertensive patients with renal insufficiency. 1615 5

Calcium antagonists comprise 2 main subclasses, dihydropyridines and nondihydropyridines, and have been studied extensively in hypertensive patients. Early meta-analyses suggested that short-acting calcium antagonists were associated with higher mortality rates resulting from cardiovascular events and other etiologies. Recent meta-analyses failed to show any substantive difference between long acting calcium antagonists and other antihypertensive drug classes with regard to cardiovascular outcomes in those with low to moderate cardiovascular risk or kidney disease progression among those with stage 2 or 3 nonproteinuric kidney diseases. The data from calcium antagonist trials are consistent in that they decrease stroke incidence but fail to protect against new-onset heart failure. In people with proteinuric kidney disease, that is > 300 mg protein/gram creatinine, use of dihydropyridine calcium antagonists to lower blood pressure without the use of agents that block the renin angiotensin aldosterone system does not provide optimal slowing of nephropathy progression. This relates directly to lack of antiproteinuric effects with this subclass and not seen with nondihydropyridine agents that reduce proteinuria to a greater degree than dihydropyridines. Thus, calcium antagonists are safe and as efficacious as other antihypertensive agents to reduce cardiovascular risk. They should be avoided in people with systolic dysfunction but may be used for blood pressure lowering in people with preserved systolic function. Dihydropyridine calcium antagonists should only be used in conjunction with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in proteinuric kidney disease because they will not optimally slow kidney function loss in their absence.
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PMID:Calcium antagonists: effects on cardio-renal risk in hypertensive patients. 1617 20

Drugs that inhibit the renin-angiotensin system (RAS), namely angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor antagonists (ARA) are gaining increasing popularity as initial medications for the management of hypertensive patients. In the year 2002, ACE-I were the most commonly prescribed drugs for the treatment of hypertension in USA. Although their antihypertensive efficacy as monotherapy is similar to other antihypertensive agents, they have the advantage of better tolerability, limited side effects and a favorable metabolic profile. When compared to other antihypertensive agents (diuretics, beta-adrenergic blockers and calcium antagonists) in large clinical trials, ACE-I and ARA provided no additional advantages regarding improvement in cardiovascular and total mortality. With the exception of the superiority of ARA in prevention of stroke, RAS inhibitors have no advantage over other agents in prevention of other cardiovascular morbid events, namely, heart failure (though ACE-I are superior to calcium antagonists), coronary heart disease and total cardiovascular events. However, there is the possibility that these agents have other benefits beyond blood pressure lowering. At equal degrees of blood pressure reduction, RAS inhibitors prevent or delay the development of diabetes mellitus and provide better end-organ protection, kidneys, blood vessels and the heart when compared with other antihypertensive agents. The combined use of ACE-I and ARA is particularly useful in organ protection. RAS inhibitors are specifically indicated in the treatment of hypertension in patients with impaired left ventricular systolic function, diabetes, proteinuria, impaired kidney function, myocardial infarction, multiple cardiovascular risk factors and possibly elderly patients. The main limitation of the ACE-I is cough and rarely angioedema. Elderly patients or those who are volume depleted or receiving large doses of diuretics or in heart failure are liable to develop hypotensive reaction and/or deterioration in kidney function.
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PMID:RAS inhibition in hypertension. 1639 19

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