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

The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study demonstrated the clinical benefit of losartan-based therapy in hypertensive patients with left ventricular hypertrophy (LVH), mainly due to a highly significant 25% reduction in the relative risk of stroke compared with an atenolol-based regimen, for a similar reduction in blood pressure. The aim of this economic evaluation was to estimate the cost-effectiveness of losartan compared with atenolol from a UK national health system perspective. Quality-adjusted survival and direct medical costs were modelled beyond the trial using the within-trial incidence of stroke. Survival with stroke, study medication use and quality of life by stroke status were taken directly from the LIFE trial. The LIFE data were supplemented with UK data on lifetime direct medical costs of stroke and life expectancy in individuals without stroke. No additional stroke events or use of study treatment were assumed beyond the trial. Costs and benefits were discounted using current UK Treasury rates. In the base-case analysis, the reduction in stroke-related costs (by 968 sterling pound) offset 86% of the increase in study medication costs (1128 sterling pound) among losartan-treated patients. The incremental cost-effectiveness ratio (ICER) for losartan versus atenolol in hypertensive patients with LVH was 2130 sterling pound per quality-adjusted life year (QALY) gained (3195 Euro/QALY), and this increased to 11,352 sterling pound per QALY gained (16,450 Euro/QALY) when the costs of stroke beyond the first 5 years were excluded. Thus, the clinical benefit of losartan was achieved at a cost well within reported thresholds for cost-effectiveness.
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PMID:Cost-effectiveness of losartan-based therapy in patients with hypertension and left ventricular hypertrophy: a UK-based economic evaluation of the Losartan Intervention for Endpoint reduction in hypertension (LIFE) study. 1675 4

Losartan (Cozaar) is an angiotensin AT1 receptor antagonist. It is approved in numerous countries for the treatment of hypertension and has been approved in the UK, the US and several European countries for stroke risk reduction in patients with hypertension and left ventricular hypertrophy (LVH). Losartan is recommended for use alone or with hydrochlorothiazide, but it can also be administered with other antihypertensive medications. In patients with hypertension, losartan effectively lowers blood pressure and also leads to regression of LVH. In the large, well designed LIFE (Losartan Intervention For Endpoint reduction in hypertension) study in patients with hypertension and LVH, losartan was more effective than atenolol in reducing the composite primary endpoint of cardiovascular (CV) mortality, stroke or myocardial infarction (MI). This was mainly due to a significant 25% reduction in the risk of stroke in the losartan group. Losartan recipients also had a significantly lower incidence of new-onset diabetes mellitus compared with atenolol recipients. Similar benefits were observed in several patient subgroups from the LIFE study, but not in the subgroup of Black patients. Losartan is well tolerated and is a cost effective alternative to atenolol in the setting of stroke reduction. Comparative data on clinical outcomes in hypertensive patients for losartan versus other antihypertensive agents would be of interest. Nonetheless, in addition to its established antihypertensive and end organ effects, the LIFE study indicates that, with the possible exception of Black patients, losartan can reduce the risk of stroke in patients with hypertension and LVH.
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PMID:Losartan: a review of its use in stroke risk reduction in patients with hypertension and left ventricular hypertrophy. 1639 83

It has been well documented that oxidative stress is involved in stroke. Currently, many neuroprotective strategies have been targeted at molecules that are able to act as an oxidant to intervene with free-radical mediated apoptosis in the ischemic penumbra. In particular, natural products which contain antioxidant properties have undoubtedly efficacious for stroke treatment. In the current study, therapeutic effects of Ginkgo biloba extract (EGb) against cerebral protection in Wistar rats underwent middle cerebral artery occlusion (MCAO) was evaluated. A comparison study was conducted by using Losartan, an antihypertensive drug. Gene expression levels of pro-apoptotic genes (AT2 receptor, Fas, Bax and Bcl-xS) have shown to have significant reduction by EGb- and Losartan-treated groups as compared to vehicle group. Significant reduction of immunoreactivity of protein production of these genes, together with least nuclear green fluorescence observed in TUNEL, EGb, as an antioxidant drug, is concluded to have potent and promising therapeutic effect for stroke treatment.
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PMID:A comparison study of cerebral protection using Ginkgo biloba extract and Losartan on stroked rats. 1644 25

In the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study, there was a 25% risk reduction for stroke with angiotensin receptor blocker-based therapy (losartan) as compared with beta-blocker-based therapy (atenolol) despite comparable blood pressure reductions. This substudy examines treatment effects on the amount and density of atherosclerotic lesions in the common carotid arteries and the carotid bulb in 81 patients during 3 years of treatment. There were no statistically significant changes in the amount of carotid plaque in patients treated with losartan compared with an atenolol-based treatment program. A statistically nonsignificant increase in plaque density and index (average of plaque amount and density) was seen in the atenolol group compared with those treated with losartan. The small number of patients evaluated may have limited the power to detect a difference in outcome. The difference in carotid plaque index increase between the treatment groups during 3 years of treatment could not be statistically linked to specific treatments in the present substudy.
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PMID:Long-term effects of a losartan- compared with an atenolol-based treatment regimen on carotid artery plaque development in hypertensive patients with left ventricular hypertrophy: ICARUS, a LIFE substudy. 1652 93

We are currently fighting a battle against a stroke epidemic. Implementation of new treatment strategies could save many patients in the future. The control of blood pressure is a major objective; however, choosing specific antihypertensive therapy (e.g. an agent blocking the renin-angiotensin system) is also important. The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study demonstrates potential benefits beyond blood pressure reduction of prescribing an angiotensin II receptor blocker (ARB) compared with more established therapy in patients with left ventricular hypertrophy (LVH). Losartan-based therapy brought about regression of LVH and reduced incidences of fatal and non-fatal stroke by 25%, new-onset diabetes by 25% and atrial fibrillation by 30% more than atenolol-based therapy for a similar blood pressure control and better tolerability. The Study on COgnition and Prognosis in the Elderly (SCOPE) study, although difficult to interpret, does not contradict an ARB benefit beyond blood pressure lowering in primary prevention linked to targeting the angiotensin type 1 receptor. The findings of the MOrbidity and mortality after Stroke, Eprosartan compared with nitrendipine in Secondary prevention (MOSES) trial suggest clear-cut ARB benefits independent of blood pressure lowering in secondary stroke prevention. Experimental findings and other clinical evidence further support the benefits of ARBs in stroke prevention. Telmisartan is an ARB with a particularly interesting profile for stroke; given the 24-hour efficacy with more pronounced protection against the morning blood pressure surge and peroxisome proliferator-activated receptor-gamma activity at clinical doses. The unique properties of telmisartan for secondary stroke prevention are being tested in the Prevention Regimen For Effectively avoiding Second Strokes (PRoFESS) study.
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PMID:Prospects for the prevention of stroke. 1660 58

The influence of left atrial size on cardiovascular events during antihypertensive treatment has not been reported previously from a long-term, prospective, randomized hypertension treatment trial. We recorded left atrial diameter by annual echocardiography and cardiovascular events in 881 hypertensive patients (41% women) with electrocardiographic left ventricular hypertrophy aged 55 to 80 (mean: 66) years during a mean of 4.8 years of randomized losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint Reduction in Hypertension Study. During follow-up, a total of 88 primary end points (combined cardiovascular death, myocardial infarction, or stroke) occurred. In Cox regression, baseline left atrial diameter/height predicted incidence of cardiovascular events (hazard ratio: 1.98 per cm/m [95% CI: 1.02 to 3.83 per cm/m]; P=0.042) adjusted for significant effects of Framingham risk score and history of atrial fibrillation. Greater left atrial diameter reduction during follow-up was associated with greater reduction in left ventricular hypertrophy, absence of new-onset atrial fibrillation or mitral regurgitation during follow-up, and losartan-based treatment (B=-0.13+/-0.03 cm/m; P<0.001) in multiple linear regression, adjusting for baseline left atrial diameter/height. However, in time-varying Cox regression analysis, left atrial diameter reduction was not independent of left ventricular hypertrophy regression in predicting cardiovascular events during follow-up. In conclusion, left atrial diameter/height predicts risk of cardiovascular events independent of other clinical risk factors in hypertensive patients with left ventricular hypertrophy and may be useful in pretreatment clinical assessment of cardiovascular risk in these patients.
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PMID:Left atrial size and risk of major cardiovascular events during antihypertensive treatment: losartan intervention for endpoint reduction in hypertension trial. 1717 78

The relation of metabolic syndrome (MetS) with cardiovascular outcome may be less evident when preclinical cardiovascular disease is present. We explored, in a post hoc analysis, whether MetS predicts cardiovascular events in hypertensive patients with electrocardiographic left ventricular hypertrophy (ECG-LVH) in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study. MetS was defined by >or=2 risk factors plus hypertension: body mass index >or=30 kg/m(2), high-density lipoprotein (HDL)-cholesterol <1.0/1.3 mmol/l (<40/50 mg/dl) (men/women), glucose >or=6.1 mmol/l (>or=110 mg/dl) fasting or >or=7.8 mmol/l (>or=140 mg/dl) nonfasting or diabetes. Cardiovascular death and the primary composite end point (CEP) of cardiovascular death, stroke and myocardial infarction were examined. In MetS (1,591 (19.3%) of 8,243 eligible patients), low HDL-cholesterol (72%), obesity (77%) and impaired glucose (73%) were similarly prevalent, with higher blood pressure, serum creatinine and Cornell product, but lower Sokolow-Lyon voltage (all P<0.001). After adjusting for baseline covariates, hazard ratios for CEPs and cardiovascular death (4.8+/-1.1 years follow-up) were 1.47 (95% confidence interval (CI), 1.27-1.71)- and 1.73 (95% CI, 1.38-2.17)-fold higher with MetS (both P<0.0001), and were only marginally reduced when further adjusted for diabetes, obesity, low HDL-cholesterol, non-HDL-cholesterol, pulse pressure and in-treatment systolic blood pressure and heart rate. Thus, MetS is associated with increased cardiovascular events in hypertensive patients with ECG-LVH, independently of single cardiovascular risk factors.
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PMID:Clusters of metabolic risk factors predict cardiovascular events in hypertension with target-organ damage: the LIFE study. 1747 91

A fixed-dose combination of losartan/hydrochlorothiazide (HCTZ) therapy may be a logical choice for antihypertensive treatment, including for initial therapy in patients with blood pressure elevation >20/10 mmHg above treatment target. The renin-angiotensin-aldosterone-system-activating effect of hydrochlorothiazide augments the efficacy of blocking the angiotensin II type 1 (AT1) receptor with losartan. Some adverse effects associated with hydrochlorothiazide, including increased risk for new-onset diabetes mellitus, may be offset by losartan. Losartan was frequently administered with hydrochlorothiazide in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, in which there was a 25% risk reduction for stroke in the losartan-based compared with the atenolol-based treatment group. The efficacy, tolerability, and convenience of losartan/HCTZ combination therapy may increase patient compliance and lower risk for stroke, a devastating outcome in patients with hypertension.
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PMID:Fixed combination of losartan and hydrochlorothiazide and reduction of risk of stroke. 1770 37

The optimal hemoglobin level in patients with hypertension or heart failure is not yet defined. The aim of the present investigation was to examine the relation of hemoglobin with cardiovascular outcomes in high-risk patients with isolated systolic hypertension (ISH) and left ventricular hypertrophy (LVH). In 1,326 patients with ISH in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study, hemoglobin and cardiovascular outcomes were examined using Cox proportional hazard models. Baseline hemoglobin was negatively related to rate of cardiovascular death (hazard ratio 0.81 per 1 g/dl, 95% confidence interval [CI] 0.67 to 0.98, p = 0.032) after adjusting for baseline Framingham risk score, LVH, treatment, and estimated glomerular filtration rate. Hemoglobin decreased slightly during the study and the decrease was more pronounced in the losartan group (13.9 +/- 1.3 to 13.6 +/- 1.4 g/dl) than in the atenolol group (13.9 +/- 1.2 to 13.8 +/- 1.4 g/dl). Hemoglobin as a time-varying covariate was negatively associated with rate of cardiovascular death (hazard ratio 0.75, 95% CI 0.63 to 0.90, p <0.001) and stroke (hazard ratio 0.84, 95% CI 0.72 to 0.99, p = 0.040) after adjusting for baseline Framingham risk score, LVH, treatment, and estimated glomerular filtration rate. In conclusion, in this high-risk population with ISH and LVH, lower hemoglobin at baseline was associated with higher probability of cardiovascular death, and decrease in hemoglobin over time was associated with higher probability of cardiovascular death or stroke; this effect was attenuated by treatment with losartan.
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PMID:Effect of hemoglobin levels on cardiovascular outcomes in patients with isolated systolic hypertension and left ventricular hypertrophy (from the LIFE study). 1771 33

We evaluated the effects of the angiotensin II (Ang II) receptor blocker (ARB) losartan on the formation and number of endothelial progenitor cells (EPCs) in hypertensive rats. Wistar-Kyoto (WKY) rats and stroke-prone, spontaneously hypertensive rats (SHR-SP) were salt-loaded and then treated with losartan (10 mg/kg/day), trichlormethiazide (TCM; 1.6 mg/kg/day), or tempol (1 mmol/L) for 2 weeks. Peripheral blood mononuclear cells were isolated, subjected to flow cytometric analysis to determine the number of circulating EPCs, cultured to assay EPC colony formation, and subjected to a migration chamber assay to evaluate EPC migration. Oxidative stress in EPCs was evaluated by thiobarbituric acid reactive substance (TBARS) assay. The results showed that the number, colony formation, and migration of EPCs were markedly decreased in SHR-SP compared to those in WKY rats. The TBARS scores were significantly greater in SHR-SP than in WKY rats. Losartan and TCM decreased systolic blood pressure in SHR-SP to similar levels. Losartan and tempol increased the number of circulating EPCs and colony formation, and inhibited oxidation in SHR-SP. TCM did not affect the EPC number, colony formation, or oxidation. Both losartan and TCM stimulated EPC migration. Expression of gp91(phox), p22(phox), and p47(phox) mRNA in tissues was significantly decreased by losartan but not by TCM. These results indicate that the formation and function of EPCs are impaired by oxidative stress in SHR-SP. This is the first report to show that losartan improves the proliferation and function of EPCs in hypertension, suggesting that ARBs are useful to repair hypertensive vascular injuries.
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PMID:Losartan improves the impaired function of endothelial progenitor cells in hypertension via an antioxidant effect. 1825 May 49


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