| 61. |
- Ibsen, H., et al.
(författare)
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Does albuminuria predict cardiovascular outcome on treatment with losartan versus atenolol in hypertension with left ventricular hypertrophy? A LIFE substudy
- 2004
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Ingår i: J Hypertens. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352. ; 22:9, s. 1805-11
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To examine a possible relationship between baseline albuminuria and effect of losartan versus atenolol on cardiovascular (CV) events in hypertensive patients with left ventricular hypertrophy, the effect of losartan versus atenolol on albuminuria, and whether the benefits of losartan versus atenolol could be explained by influence of losartan on albuminuria. DESIGN: Double-blind, randomized, controlled trial of 4.8 years. SETTING: Out-patient setting. PATIENTS: A total of 8206 with hypertension and left ventricular hypertrophy. INTERVENTIONS: Losartan or atenolol, supplemented with diuretics and/or calcium antagonists to reach blood pressure < 140/90 mmHg MAIN OUTCOME MEASURES: The urine albumin/creatinine ratio, and the primary composite endpoint (CEP) of CV death, myocardial infarction, and stroke. RESULTS: The blood pressure was reduced similarly on losartan (30.2/16.6 mmHg) versus atenolol (29.1/16.8 mmHg). The risk of a primary CEP increased linearly from the lowest to the highest decile of baseline albuminuria. The benefits of losartan versus atenolol for the primary CEP and for stroke tended to be more pronounced among patients above the median value for baseline albuminuria (urine albumin/creatinine ratio, 1.28 mg/mmol). The decrease in albuminuria was significantly greater with losartan versus atenolol throughout the study (a decrease from baseline to year 2 of 33% losartan versus 25% atenolol). One-fifth of the difference in favor of losartan on the primary CEP was explained by the greater reduction in albuminuria on losartan. CONCLUSIONS: Baseline albuminuria is a powerful risk factor for CV events. Baseline albuminuria did not identify the group of patients with greatest benefit on losartan versus atenolol in LIFE. Reduction in albuminuria explained one-fifth of the benefits of losartan versus atenolol.
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| 62. |
- Ibsen, H., et al.
(författare)
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Does albuminuria predict cardiovascular outcomes on treatment with losartan versus atenolol in patients with diabetes, hypertension, and left ventricular hypertrophy? The LIFE study
- 2006
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Ingår i: Diabetes Care. - 0149-5992. ; 29:3, s. 595-600
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Our current aims were to investigate whether 1) baseline urinary albumin-to-creatinine ratio (UACR) predicted cardiovascular outcomes, 2) changes in UACR differed between treatments, 3) benefits of losartan were related to its influence on UACR, and 4) reduction in albuminuria reduced cardiovascular events. RESEARCH DESIGN AND METHODS: In 1,063 patients with diabetes, hypertension, and left ventricular hypertrophy, UACR was measured for a mean of 4.7 years. The primary composite end point included cardiovascular death, myocardial infarction, and stroke. Cox models were run including and excluding baseline and time-varying UACR. RESULTS: Increasing baseline albuminuria related to increased risk for cardiovascular events. Reductions in UACR at years 1 and 2 were approximately 33% for losartan vs. 15% for atenolol (P < 0.001). Benefits of losartan seem to be most prominent in patients with the highest level of baseline UACR, although treatment by albuminuria interaction was only significant for total mortality. Approximately one-fifth of the superiority of losartan was explained by the greater reduction of albuminuria. Risk of the primary end point was related to the in-treatment UACR. CONCLUSIONS: Lowering of albuminuria in patients with hypertension and diabetes appears to be beneficial and should be the subject of additional study in future clinical trials.
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| 63. |
- Ibsen, H., et al.
(författare)
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Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: losartan intervention for endpoint reduction in hypertension study
- 2005
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Ingår i: Hypertension. - 1524-4563. ; 45:2, s. 198-202
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Tidskriftsartikel (refereegranskat)abstract
- Few data are available to clarify whether changes in albuminuria over time translate to changes in cardiovascular risk. The aim of the present study was to examine whether changes in albuminuria during 4.8 years of antihypertensive treatment were related to changes in risk in 8206 patients with hypertension and left ventricular hypertrophy in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Urinary albumin/creatinine ratio (UACR) was measured at baseline and annually. Time-varying albuminuria was closely related to risk for the primary composite end point (ie, when UACR decreased during treatment, risk was reduced accordingly). When the population was divided according to median baseline value (1.21 mg/mmol) and median year 1 UACR (0.67 mg/mmol), risk increased stepwise and significantly for the primary composite end point from those with low baseline/low year 1 (5.5%), to low baseline/high year 1 (8.6%), to high baseline/low year 1 (9.4%), and to high baseline/high year 1 (13.5%) values. Similar significant, stepwise increases in risk were seen for the components of the primary composite end point (cardiovascular mortality, stroke, and myocardial infarction). The observation that changes in UACR during antihypertensive treatment over time translated to changes in risk for cardiovascular morbidity and mortality was not explained by in-treatment level of blood pressure. We propose that monitoring of albuminuria should be an integrated part of the management of hypertension. If albuminuria is not decreased by the patient's current antihypertensive and other treatment, further intervention directed toward blood pressure control and other modifiable risks should be considered.
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| 64. |
- Jamerson, K. A., et al.
(författare)
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Rationale and design of the avoiding cardiovascular events through combination therapy in patients living with systolic hypertension (ACCOMPLISH) trial: the first randomized controlled trial to compare the clinical outcome effects of first-line combination therapies in hypertension
- 2004
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Ingår i: Am J Hypertens. - : Oxford University Press (OUP). - 0895-7061. ; 17:9, s. 793-801
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Tidskriftsartikel (refereegranskat)abstract
- Reducing blood pressure (BP) to target levels is a major priority in preventing clinical events in hypertension. Typically this requires more than one drug, and recent guidelines on hypertension management therefore recommend starting with combination treatment in many patients. Diuretics have often been part of such therapy, usually paired with angiotensin converting enzyme (ACE) inhibitors or similar agents; but calcium channel blockers are also highly efficacious in reducing BP when combined with ACE inhibitors. In addition, these drug classes, separately and in combination, appear to have vasculoprotective properties. Because the primary goal of treating hypertension is to enhance survival and reduce cardiovascular outcomes, the Rationale and Design of Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) trial is designed as the first blinded and randomized study to prospectively compare the effects on these endpoints of two antihypertensive combinations, benazapril/hydrochlorothiazide (force titrated to 40/12.5 mg) and amlodipine besylate/benazapril (force titrated to 5/40 mg). The doses can be further titrated to 40/25 mg or 10/40 mg, and other classes of drugs can be added as needed for optimal BP control. The primary study endpoint is a composite of cardiovascular mortality and morbidity. The study will be performed in hypertensive patients (systolic BP > or = 160 mm Hg or currently on antihypertensive therapy) with risk factors for cardiovascular events (prior events, target organ damage, kidney disease, or diabetes). A total of 6300 subjects will be randomized to each group with the expectation that a total of 1642 primary endpoints will occur during a 5-year period, providing 90% power to detect the 15% relative reduction in events (alpha = 0.05) hypothesized to favor the amlodipine besylate/benazapril group. The ACCOMPLISH study will be performed in the United States and Europe. The first patient was randomizedduring 2003, and the trial should conclude in 2008.
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| 65. |
- Jamerson, K., et al.
(författare)
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Exceptional early blood pressure control rates: the ACCOMPLISH trial
- 2007
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Ingår i: Blood Press. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 16:2, s. 80-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: ACCOMPLISH is a "new-generation" hypertension trial assessing single-tablet combination therapy for initial treatment of high-risk hypertension. At baseline, 97% of subjects were treated with anti-hypertensive medication at entry, but only 37% of participants had blood pressure (BP) control (<140/90 mmHg). Single-tablet combination therapy may improve control rates. METHODS: The mean BP change from baseline at the end of 6 months (the time point when subjects should have had all of the drug titrations to achieve BP control) was examined for 10,704 randomized patients. Within-group changes were examined using t-tests. Comparisons between subgroups were made using analysis of variance (ANOVA) and covariance (ANCOVA). RESULTS: Mean (+/-SD) BP fell from 145+/-18/80+/-11 mmHg at randomization to 132+/-16/74+/-10 mmHg. The 6-month BP control rate was 73% in the overall trial (78% in the US), 43% in diabetics and 40% in patients with renal disease. Of the patients uncontrolled, 61% were not on maximal medications, suggesting potential increases in control rates. Serious hypotensive events occurred in 1.8% of participants. CONCLUSION: ACCOMPLISH BP control rates are the highest of any multi-national trial to date. Whereas current guidelines recommend combination therapy only for stage 2 hypertension, in this trial it is expedient and safe for both stage 1 and 2 hypertension.
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| 66. |
- Jern, Sverker, 1954, et al.
(författare)
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Swedish Isradipine Study in Hypertension: evaluation of quality of life, safety, and efficacy. SWISH Group.
- 1991
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 18 Suppl 3, s. S7-8
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Tidskriftsartikel (refereegranskat)abstract
- This was a double-blind multicenter study to compare the efficacy, tolerability and effects on the quality of life with isradipine and atenolol in the treatment of essential hypertension. Of 588 patients entering the 6-week placebo run-in period, 549 were eligible for randomization to receive either isradipine or atenolol for 8 weeks. If, at the end of this period, diastolic blood pressure (DBP) remained greater than 90 mm Hg, then both agents were given in combination for a further 10 weeks. Tolerability and quality of life were assessed repeatedly during the placebo and active-treatment phases. A subgroup of 30 patients were followed by 24-h ambulatory blood pressure monitoring, and their results are now being analyzed. In another subgroup of 26 patients, maximum exercise capacity, as determined by ergometer bicycle-testing, was measured once during placebo and twice during active treatment. At the end of the 24-week study period, both isradipine and atenolol as monotherapy had produced significant decreases in blood pressure. There were no significant differences overall between the compounds in quality-of-life and side-effect profiles, although there was a relative absence of ankle edema and headache with isradipine. Furthermore, patients receiving isradipine had no change in performance on exercise testing whereas patients on atenolol had a significant decrease (p less than 0.01).
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| 67. |
- Jing, F., et al.
(författare)
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Direct stimulation of angiotensin II type 2 receptor enhances spatial memory
- 2012
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Ingår i: Journal of cerebral blood flow and metabolism. - : SAGE Publications. - 1559-7016 .- 0271-678X. ; 32
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Tidskriftsartikel (refereegranskat)abstract
- We examined the possibility that direct stimulation of the angiotensin II type 2 (AT(2)) receptor by a newly generated direct AT(2) receptor agonist, Compound 21 (C21), enhances cognitive function. Treatment with C21 intraperitoneal injection for 2 weeks significantly enhanced cognitive function evaluated by the Morris water maze test in C57BL6 mice, but this effect was not observed in AT(2) receptor-deficient mice. However, C21-induced cognitive enhancement in C57BL6 mice was attenuated by coadministration of icatibant, a bradykinin B(2) receptor antagonist. Administration of C21 dose dependently increased cerebral blood flow assessed by laser speckle flowmetry and hippocampal field-excitatory postsynaptic potential (f-EPSP) determined by electrophysiological techniques in C57BL6 mice. Furthermore, activation of the AT(2) receptor by C21 promoted neurite outgrowth of cultured hippocampal neurons prepared from fetal transgenic mice expressing green fluorescent protein. Finally, we investigated the pathologic relevance of C21 for spatial learning using an Alzheimer's disease mouse model with intracerebroventricular injection of amyloid-beta (1 to 40). We observed that treatment with C21 prevented cognitive decline in this model. These results suggest that a direct AT(2) receptor agonist, C21, enhances cognitive function at least owing to an increase in CBF, enhancement of f-EPSP, and neurite outgrowth in hippocampal neurons.Journal of Cerebral Blood Flow & Metabolism advance online publication, 5 October 2011; doi:10.1038/jcbfm.2011.133.
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| 68. |
- Jonsson, B., et al.
(författare)
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Cost effectiveness of losartan in patients with hypertension and LVH: an economic evaluation for Sweden of the LIFE trial
- 2005
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Ingår i: J Hypertens. - 0263-6352. ; 23:7, s. 1425-31
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Evaluate the cost effectiveness of losartan compared with atenolol from a Swedish national health system perspective. DESIGN: The Losartan Intervention For Endpoint reduction in hypertension study (LIFE) was a double-masked, randomized trial of losartan versus atenolol in 9193 patients with essential hypertension and left ventricular hypertrophy (LVH) ascertained by electrocardiography. Losartan reduced the primary composite end point of cardiovascular death, myocardial infarction (MI), or stroke by 13% (P = 0.021) and reduced the risk of stroke by 25% (P = 0.001), despite a comparable degree of blood pressure control. METHODS: Life years gained was estimated by combining the absolute risk reduction in stroke with the life years gained by preventing stroke. Quality-adjusted life years (QALYs) gained was estimated by combining the absolute risk reduction in stroke with the QALYs gained by preventing stroke. QALYs were estimated by weighting life years by health-related quality of life (QoL), as measured with visual analogue scale (VAS) data collected in the trial. Net costs were defined as the total of study medication cost, stroke-related costs, and costs of increased survival. Costs are in 2003 Swedish prices. All costs and effects were discounted at a 3% annual rate. RESULTS: Prevention of a stroke resulted in a gain of 5.7 life years and 4.3 QALYs. As a consequence, losartan treatment resulted in a per patient increase of 0.092 life years [95% confidence interval (CI): 0.038, 0.146] and 0.069 QALYs (95% CI: 0.028, 0.109) as compared with atenolol treatment. Losartan reduced direct stroke-related cost per patient by 1141 euros due to a lower cumulative incidence of stroke for losartan at 5.5 years (4.9%) as compared with atenolol (6.5%) (95% CI of difference: 0.7, 2.5). The reduction in stroke-related cost offset 80% of the added cost of losartan drug therapy. After inclusion of study medication cost, net cost per patient was 289 euros higher for losartan than atenolol. The net cost per QALY gained for losartan was 4188 euros (37,813 SEK), which is well within common Swedish benchmark upper values (200-500,000 SEK) for accepted cost-effective interventions. CONCLUSION: Based on the results from the LIFE trial, treatment with losartan compared with atenolol, in hypertensive patients with LVH, is a cost-effective intervention.
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| 69. |
- Julius, S., et al.
(författare)
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Cardiovascular risk reduction in hypertensive black patients with left ventricular hypertrophy: the LIFE study
- 2004
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Ingår i: J Am Coll Cardiol. - 0735-1097. ; 43:6, s. 1047-55
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We report on a subanalysis of the effects of losartan and atenolol on cardiovascular events in black patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. BACKGROUND: The LIFE study compared losartan-based to atenolol-based therapy in 9,193 hypertensive patients with left ventricular hypertrophy (LVH). Overall, the risk of the primary composite end point (cardiovascular death, stroke, myocardial infarction) was reduced by 13% (p = 0.021) with losartan, with similar blood pressure (BP) reduction in both treatment groups. There was a suggestion of interaction between ethnic background and treatment (p = 0.057). METHODS: Exploratory analyses were performed that placed LIFE study patients into black (n = 533) and non-black (n = 8,660) categories, overall, and in the U.S. (African American [n = 523]; non-black [n = 1,184]). RESULTS: A significant interaction existed between the dichotomized groups (black/non-black) and treatment (p = 0.005); a test for qualitative interaction was also significant (p = 0.016). The hazard ratio (losartan relative to atenolol) for the primary end point favored atenolol in black patients (1.666 [95% confidence interval (CI) 1.043 to 2.661]; p = 0.033) and favored losartan in non-blacks (0.829 [95% CI 0.733 to 0.938]; p = 0.003). In black patients, BP reduction was similar in both groups, and regression of electrocardiographic-LVH was greater with losartan. CONCLUSIONS: Results of the subanalysis are sufficient to generate the hypothesis that black patients with hypertension and LVH might not respond as favorably to losartan-based treatment as non-black patients with respect to cardiovascular outcomes, and do not support a recommendation for losartan as a first-line treatment for this purpose. The subanalysis is limited by the relatively small number of events.
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| 70. |
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