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Query: UMLS:C0038454 (stroke)
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The 'Perindopril protection against recurrent stroke study' (PROGRESS) demonstrated that for patients with a history of stroke or transient ischaemic attack during the previous 5 years, a blood-pressure-lowering regimen based on the combination of a diuretic and an angiotensin-converting enzyme (ACE) inhibitor, reduces the risk of stroke recurrence (fatal and non-fatal) by 28% (95%-CI: 17-38). This effect was irrespective of the initial neurological diagnosis (ischaemic or haemorrhagic stroke) and blood pressure level. Patients who were treated with just the ACE inhibitor did not exhibit these effects. This large-scale clinical trial demonstrates that hypotensive medication in the form of a diuretic combined with an ACE inhibitor is a beneficial strategy for the secondary prevention of stroke in normotensive and hypertensive patients.
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PMID:[Reduced risk of stroke recurrence due to hypotensive medication, irrespective of the initial blood pressure]. 1203 29

1. The burden of stroke worldwide is growing rapidly, driven by an ageing population and by the rapid rate of urbanization and industrialization in the developing world. There are approximately 5 million fatal and 15 million non-fatal strokes each year and over 50 million survivors of stroke alive, worldwide, today. 2. The most important determinant of stroke risk is blood pressure, with a strong, continuous relationship between the level of the systolic and diastolic pressures and the risk of initial and recurrent stroke, in both Western and Asian populations. 3. Randomized clinical trials have clearly demonstrated that blood pressure lowering reduces the risk of initial stroke by 35-40% in hypertensive patients; but, until recently, there was no conclusive evidence that blood pressure lowering was effective in the secondary prevention of stroke. 4. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) has provided definitive evidence that blood pressure lowering in patients with previous stroke or transient ischaemic attack (TIA) reduces the incidence of secondary stroke by 28%, of major vascular events by 26% and of major coronary events by 26%. These reductions were all magnified by approximately 50% in a subgroup of patients in whom the angiotensin-converting enzyme inhibitor perindopril was routinely combined with the diuretic indapamide. 5. Successful global implementation of a treatment with perindopril and indapamide in patients with a history of stroke or TIA would markedly reduce the burden of stroke and could avert between 0.5 and one million strokes each year, worldwide.
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PMID:Progress in reducing the burden of stroke. 1190 23

Blood pressure levels are strongly predictive of the risks of first-ever and recurrent stroke. The benefits of blood pressure-lowering therapy for the prevention of fatal and non-fatal stroke in middle-aged individuals are well established. However, until recently, there has been uncertainty about the consistency of such benefits across different patient groups and in particular, for older people and in those with a history of stroke. This paper discusses the evidence surrounding the effectiveness of blood pressure-lowering therapy, specifically in older patients with a history of stroke, with particular attention paid to the results from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). PROGRESS was a randomised, double-blind, placebo-controlled trial of 6105 individuals with a history of cerebrovascular disease recruited from 172 hospital outpatient clinics in ten countries. Participants (mean age 64 years; range 26-91 years) were randomly assigned to receive active treatment with an ACE inhibitor-based blood pressure-lowering regimen (perindopril) with or without addition of the diuretic indapamide, or matched placebo. At the end of follow up (mean of 4 years), active treatment reduced the incidence of total stroke by 28% (95% CI 17-38%) and the rate of major vascular events by 26% (95% CI 16-34%). Importantly, benefits of treatment were consistent across key patient subgroups, including those with and without hypertension, patients who were Asian and non-Asian, and for both ischaemic and haemorrhagic strokes subtypes. Current evidence is now strong for clinicians to consider blood pressure-lowering therapy as pivotal in the prevention of stroke, especially in patients with a known history of cerebrovascular disease (and vascular disease, in general), irrespective of blood pressure levels, as soon as patients are clinically stable after an acute stroke or other vascular event. Additional age-specific analyses of the PROGRESS data, together with those from other completed trials, will provide more reliable information about the size of the benefits of blood pressure-lowering therapy, specifically for different age groups, and particularly in the oldest old (those aged >80 years). In the meantime though, an ACE inhibitor plus diuretic treatment regimen that maximises the degree of blood pressure reduction has a good safety profile and is an effective treatment that should be considered in all patients with stroke, including the elderly.
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PMID:The Perindopril Protection Against Recurrent Stroke Study (PROGRESS): clinical implications for older patients with cerebrovascular disease. 1264 80

The risk of stroke is strongly and persistently related to the usual level of both systolic blood pressure (SBP) and diastolic blood pressure (DBP). This relation holds for primary and secondary stroke, both ischemic and hemorrhagic. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) has now provided definitive evidence that lowering the blood pressure of patients with preexisting cerebrovascular disease (prior stroke or transient ischemic attack [TIA]) also reduces the incidence of secondary stroke. PROGRESS showed that a flexible blood pressure-lowering regimen involving an angiotensin-converting enzyme inhibitor (perindopril) and a diuretic (indapamide) reduces the incidence of stroke, major coronary events, and major vascular events by 28%, 26%, and 26%, respectively. These benefits were associated with an average reduction of 9.0 mm Hg (SBP) and 4.0 mm Hg (DBP). The 28% reduction in stroke incidence translated into a 24% reduction in ischemic stroke and a 50% reduction in hemorrhagic stroke. Combination therapy with perindopril and indapamide decreased blood pressure more effectively than did perindopril monotherapy (mean reduction of 12.3 mm Hg [SBP] and 5.0 mm Hg [DBP] vs 4.9 mm Hg [SBP] and 2.8 mm Hg [DBP], respectively) and was equally effective in reducing stroke risk in patients with and without hypertension. In conclusion, blood pressure-lowering therapy is now established as the most important measure for primary and secondary stroke prevention. Results of PROGRESS suggest that antihypertensive treatment with a combination of perindopril plus indapamide should now be routinely considered for all patients with previous stroke or TIA.
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PMID:Trials on blood pressure-lowering and secondary stroke prevention. 1278 2

High blood pressure is a known risk factor for stroke and dementia. However, very little is known about the prevention of dementia by lowering blood pressure. Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) was designed to determine the effects of an angiotensin-converting enzyme (ACE) inhibitor-based blood pressure-lowering regimen on the risk of stroke among individuals with a prior stroke or transient ischaemic attack (TIA). One of the important aims of the study was to test the hypothesis that treatment would reduce the incidence of dementia and cognitive decline. A total of 6105 patients were randomized to active treatment or placebo. Active treatment comprised perindopril for all participants, and indapamide for those with neither a specific indication for, nor a contraindication to, a diuretic. Dementia was diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Cognitive decline was defined as a drop of 3 points or more on the Mini-Mental State Examination (MMSE) between baseline and final follow-up. During a median follow-up of 3.9 years, dementia was diagnosed in 410 patients and cognitive decline in 610. Active treatment reduced the risk of cognitive decline (risk reduction [RR] 19%; 95% confidence interval [CI], 4-32; P = 0.01] but there was no clear reduction in the risk of dementia (RR, 12%; 95% CI, -8-28; P = 0.2]). The RR for cognitive outcomes preceded by a recurrent stroke was 34% (95% CI, 3-55; P = 0.03) for dementia and 45% (95% CI, 21-61; P = <0.001) for cognitive decline. Among individuals with a history of stroke or TIA, blood pressure-lowering treatment reduced the risk of cognitive decline by about one fifth. Cognitive decline and dementia associated with recurrent stroke during follow-up were each reduced by between one third and one half. These findings provide further support for the recommendation that blood pressure lowering with perindopril and indapamide be considered for all patients with cerebrovascular disease.
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PMID:Vascular factors and cognition: toward a prevention of dementia? 1295 51

The most important issues facing clinicians is the transfer of evidence from clinical trials into practice. Physician, patient and community acceptance of the evidence are key components of this process. Although barriers to this exist, in the case of transfer of evidence from the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) into clinical practice, these are minimal. Hence, transfer of this information into clinical practice should put blood pressure lowering in place as the fourth major secondary prevention strategy for stroke.
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PMID:PROGRESS results: implementation in stroke guidelines. 1295 53

High blood pressure is a major risk factor for stroke and is also closely correlated with cognitive decline and dementia. Indeed, most longitudinal studies showed that cognitive functioning is often inversely proportional to blood pressure values measured 15 or 20 years previously. Because of the aging of the population, the frequency of stroke and dementia will dramatically increase in the coming years. Therefore, the prevention of cerebrovascular and cognitive disorders represents a major challenge. Antihypertensive drugs have shown clinical benefits in both primary and secondary prevention of strokes. Consensus is generally that blood-pressure lowering represents the major determinant of the benefit conferred by the antihypertensive treatment for stroke prevention; however, recent studies have suggested some differences between classes of antihypertensive drugs. The results of therapeutic trials (Systolic Hypertension in Europe, Perindopril Protection Against Recurrent Stroke Study [PROGRESS]) open the way to the prevention of dementia (vascular or Alzheimer's type) by antihypertensive treatments. These two studies suggest different mechanisms for the prevention of cognitive decline using antihypertensive drugs. In this context, reduced incidence of dementia should be the primary outcome of future trials comparing different classes of antihypertensive drugs.
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PMID:Prevention of dementia and cerebroprotection with antihypertensive drugs. 1512 72

Elevated blood pressure (BP) is frequent after acute stroke and almost 40% of patients remain hypertensive over a period of about a week. There is no data from controlled trials concerning management of hypertension in the acute phase of stroke. Theorical beneficial effects of acutely lowering BP seems lower that risk of deterioration of ischemic brain tissue. Current acute ischemic stroke guidelines suggest that unless systolic BP exceeds an cutoff of 220 mmHg or diastolic exceeds 120 mmHq, it should be tolerated, except in planned thrombolytic therapy. In case of hemorragic stroke, the cutoff should be of 185/110 mmHg. Prudence suggests that BP should be lowered carefully. In secondary prevention of stroke, the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) demonstrated that a blood pressure-lowering regimen, involving a angiotensin-converting enzyme inhibitor and a diuretic, reduced the risks of stroke of 28% and of other major vascular events of 26% among individuals with a history of cerebrovascular disease. Every patient with a history of stroke should be treated with the association.
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PMID:[Hypertension in the acute phase and in the secondary prevention of stroke]. 1522 15

A number of placebo-controlled randomized clinical trials have clearly established that blood pressure (BP) lowering, based on all antihypertensive drugs studied, lowers the risk of all major BP-related cardiovascular events. However, this does not exclude that some antihypertensive agents are more or less effective in preventing cardiovascular events than to be expected from the extent of BP lowering. Indeed, clinical trials of thiazide diuretics using 'high' doses demonstrated marked prevention of strokes, but little to no prevention of coronary events. Subsequent studies using thiazides at 'lower' doses showed prevention of both strokes and coronary events. Angiotensin converting enzyme inhibitors and calcium channel blockers exert direct vascular effects which may inhibit atherosclerosis and prevent cardiovascular events, in addition to their benefits related to BP lowering. After the publication of the results of Heart Outcome Prevention Evaluation (HOPE) trial, this concept has become widely accepted for angiotensin-converting enzyme inhibitors. However, placebo-controlled trials, such as HOPE and, recently, the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA), are confounded by the difference in BP and its impact on outcome. Indeed, as a mirror image of these trials, the blacks subgroup in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) exhibited a 4 to 5 mmHg higher systolic BP on ACE inhibitor as compared with the diuretic, associated with 19% higher combined cardiovascular disease and 40% higher stroke rate. Recent overviews of randomized clinical trials comparing outcomes with different antihypertensive drug classes concluded that outcome benefits beyond BP lowering remain unproven.
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PMID:Blood pressure lowering, not vascular mechanism of action, is the primary determinant of clinical outcome. 1530 9

B-type natriuretic peptide (BNP) and C-reactive protein (CRP) are elevated in persons at risk for congestive heart failure (CHF). However, limited data are available directly comparing BNP-related peptides and CRP in persons at risk of CHF. To evaluate amino terminal-pro-BNP (NT-proBNP) and CRP, separately and together, for assessment of risk of CHF, we performed a nested case-control study of the 6105 participants of the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure-lowering regimen among individuals with previous stroke or transient ischemic attack (TIA). Each of 258 subjects who developed CHF resulting in death, hospitalization, or withdrawal of randomized therapy during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. NT-proBNP and CRP predicted CHF; the odds ratio for subjects in the highest compared with the lowest quarter was 4.5 (95% confidence interval, 2.7 to 7.5) for NT-proBNP and 2.9 (confidence interval, 1.9 to 4.7) for CRP, and each remained a predictor of CHF after adjustment for all other predictors. Screening for both markers provided better prognostic information than screening for either alone. Elevation of NT-proBNP above 50 pmol/L and CRP above 0.84 mg/L predicted CHF with sensitivity of 64% and specificity of 66%. NT-proBNP and CRP predicted CHF in subjects receiving perindopril-based therapy. We conclude that NT-proBNP and CRP are independent predictors of CHF risk after stroke or TIA. Moreover, NT-proBNP and CRP may be markers of mechanisms of CHF pathogenesis distinct from those responsive to angiotensin-converting enzyme inhibitor-based therapy.
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PMID:Prediction of heart failure by amino terminal-pro-B-type natriuretic peptide and C-reactive protein in subjects with cerebrovascular disease. 1556 51

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