Cozaar scientific update |
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J Am Soc Nephrol. 2007 May 9;
Hou FF, Xie D, Zhang X, Chen PY, Zhang WR, Liang M, Guo ZJ, Jiang JP.
*Renal Division, Nanfang Hospital, and Department of Biostatistics, Southern Medical University, Guangzhou, People's Republic of China.
Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: A Randomized Controlled Study of Benazepril and Losartan in Chronic Renal Insufficiency.
Evidences for renoprotection of Optimal Antiproteinuric Doses (ROAD): a randomized controlled study in patients with chronic renal insufficiency using benazepril and losartan. The Renoprotection of Optimal Antiproteinuric Doses (ROAD) study was performed to determine whether titration of
benazepril or losartan to optimal antiproteinuric doses would safely improve the renal outcome in chronic renal
insufficiency. A total of 360 patients who did not have diabetes and had proteinuria and chronic renal
insufficiency were randomly assigned to four groups. Patients received open-label treatment with a conventional
dosage of benazepril (10 mg/d), individual uptitration of benazepril (median 20 mg/d; range 10 to 40), a
conventional dosage of losartan (50 mg/d), or individual uptitration of losartan (median 100 mg/d; range 50 to
200). Uptitration was performed to optimal antiproteinuric and tolerated dosages, and then these dosages were
maintained. Median follow-up was 3.7 yr. The primary end point was time to the composite of a doubling of the serum
creatinine, ESRD, or death. Secondary end points included changes in the level of proteinuria and the rate of
progression of renal disease. Compared with the conventional dosages, optimal antiproteinuric dosages of benazepril
and losartan that were achieved through uptitration were associated with a 51 and 53% reduction in the risk for the
primary end point (P = 0.028 and 0.022, respectively). Optimal antiproteinuric dosages of benazepril and losartan,
at comparable BP control, achieved a greater reduction in both proteinuria and the rate of decline in renal
function compared with their conventional dosages. There was no significant difference for the overall incidence of
major adverse events between groups that were given conventional and optimal dosages in both arms. It is concluded
that uptitration of benazepril or losartan against proteinuria conferred further benefit on renal outcome in
patients who did not have diabetes and had proteinuria and renal insufficiency.
Hypertens Res. 2007 Jan;30(1):49-53.
Bahadir O, Uzunlulu M, Oguz A, Bahadir MA.
Department of Internal Medicine, Goztepe Training and Research Hospital, Istanbul, Turkey.
Effects of telmisartan and losartan on insulin resistance in hypertensive patients with metabolic syndrome.
Effectiveness of telmisartan and losartan on insulin resistance: a study in hypertensive patients with metabolic syndrome. Partial peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists are known to decrease insulin
resistance. Experimental studies have shown that the angiotensin type 1 receptor blocker (ARB) telmisartan has a
PPAR-gamma-activating property, but there does not appear to be a class effect. To test telmisartan's clinical
importance, we here investigated its effect on insulin resistance in hypertensive patients with metabolic syndrome
(MetS) in comparison with another ARB, losartan. A total of 42 hypertensive MetS patients (29 female, 13 male) were
included (mean age: 50+/-9, range: 20-70 years). NCEP-ATP III criteria were used for the diagnosis of MetS.
Patients were randomized to receive either telmisartan 80 mg/day (n=21) or losartan 50 mg/day (n=21) for 8 weeks.
Biochemical assessments were made at baseline and at the end of the 8 weeks. Insulin resistance was evaluated by
using homeostasis model assessment of insulin resistance (HOMA-IR). Both groups had similar reductions in systolic
and diastolic pressures (p>0.05). HOMA-IR did not change significantly in either group throughout the study. In the
telmisartan group, the mean HOMA-IR at baseline and at the end of the study were 1.9+/-07 and 1.9+/-0.5,
respectively. The figures for the losartan group were 1.8+/-0.6 and 1.8+/-0.6, corresponding. In conclusion, in
contrast with the reports that telmisartan may decrease insulin resistance by an effect associated with its
molecular structure, 8 weeks of telmisartan treatment in the present study had a neutral effect on insulin
resistance in hypertensive MetS patients, and similar results were obtained for losartan.
Ren Fail. 2007;29(4):441-6.
Horita Y, Tadokoro M, Taura K, Ashida R, Hiu M, Taguchi T, Furusu A, Kohno S.
Division of Nephrology, Department of Medicine, National Hospital Organization, Nagasaki Medical Center; and Department of Internal Medicine, Nagasaki Municipal Medical Center. Nagasaki. Japan.
Prednisolone co-administered with losartan confers renoprotection in patients with IgA nephropathy.
Renoprotection in patients with IgA nephropathy can be conferred by using prednisolone along with losartan. Background.Treatment options for progressive IgA nephropathy are limited. Methods. We performed a small, randomized
controlled trial to evaluate the effects of prednisolone (PSL, 30 mg/dL, gradually tapered to 5 mg/dL over two
years) plus 50 mg/day of losartan (LST, an angiotensin II receptor blocker) or PSL alone on IgA nephropathy. We
separated 38 patients (age, 33 +/- 11 years; creatinine clearance, 103 +/- 31 mL/min; proteinuria, 1.6 +/- 0.5
g/day) into two groups that were treated with either PSL plus LST or PSL alone, and compared the proteinuria and
creatinine clearance after two years. Baseline and histopathological data did not significantly differ between the
two groups. Results. Two years of treatment in both groups significantly decreased proteinuria compared with
baseline, and PSL plus LST (from 1.6 +/- 0.6 to 0.3 +/- 0.1 g/day, p < 0.05) was more effective than PSL alone
(from 1.6 +/- 0.3 to 0.5 +/- 0.1 g/day, p < 0.05). Creatinine clearance in both groups was similar at the start of
study but significantly differed at the end of the study (PSL plus LST, 104.3 +/- 36.4 to 100.4 +/- 38.9 mL/min;
PSL alone, 103.4 +/- 28.5 to 84.8 +/- 34.3 mL/min, p < 0.05). Conclusions. Combined therapy with PSL plus LST
appears to be more effective than PSL alone in reducing proteinuria and protecting renal function in patients with
IgA nephropathy.
Diabetes Care. 2006 Oct;29(10):2210-2217.
Winkelmayer WC, Zhang Z, Shahinfar S, Cooper ME, Avorn J, Brenner BM.
ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, 1620 Tremont St., Suite 3030, Boston, MA 02120.
Efficacy and Safety of Angiotensin II Receptor Blockade in Elderly Patients With Diabetes.
Angiotensin II Receptor Blockade: effect and safety in elderly patients with diabetes. OBJECTIVE: While national guidelines recommend ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy in patients with diabetes and nephropathy, guidelines concerning elderly patients with diabetes have not endorsed these drugs. We sought to assess the nephroprotective efficacy and safety of ARB therapy in elderly patients by conducting age-specific subgroup analyses using data from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. RESEARCH DESIGN AND METHODS: We studied 1,513 patients with type 2 diabetes and nephropathy who randomly received either losartan or placebo. We tested for effect modification by age of the effect of losartan on the incidence of the predefined end points (doubling of serum creatinine, end-stage renal disease [ESRD], or death) and the risk of adverse events. RESULTS: Of 1,513 participants, 421 (27.8%) were aged >65 years (maximum age 74 years). Age did not modify the efficacy of losartan in reducing the risk of the primary outcome, a composite of doubling of serum creatinine, ESRD, or death (P(interaction) = 0.66) or its individual components (all P(interaction) > 0.44). In patients aged >65 years, losartan reduced the risk of ESRD by 50% (95% CI 30-81, P = 0.005). We found no evidence that older patients were more likely to experience adverse events from losartan such as a rise in serum creatinine or hyperkalemia than younger patients. CONCLUSIONS: Elderly patients had the same level of benefits and risks as younger patients from treatment with losartan. Underuse of ACEI and ARB therapy in elderly patients because of the perceived lack of efficacy or a greater risk of adverse events appears unjustified.
J Card Fail. 2004 Oct;10(5):412-20.
Tanaka H, Oki T, Tabata T, Yamada H, Harada K, Kimura E, Oishi Y, Ishimoto T, Ito S.
Department of Digestive and Cardiovascular Medicine, School of Medicine, The University of Tokushima, Japan.
Losartan improves regional left ventricular systolic and diastolic function in patients with hypertension: accurate evaluation using a newly developed color-coded tissue doppler imaging technique.
Regional left ventricular systolic and diastolic function in hypertensive patients can be improved by taking Losartan: precise assessment using a recently developed color-coded tissue doppler imaging technique. BACKGROUND: Angiotensin II receptor antagonists have recently been accepted as antihypertensive therapy. Tissue Doppler imaging (TDI) has been developed as a noninvasive tool to assess quantitatively regional myocardial motion abnormalities. This study was designed to determine whether our newly developed technique of color-coded TDI may be a useful means of quantifying the improvement in regional left ventricular (LV) myocardial contractility and relaxation after treatment with losartan in patients with hypertension. METHODS AND RESULTS: Losartan (50 to 100 mg) was administered for 6 months to 37 previously untreated patients with essential hypertension. Averaged myocardial velocity profiles (MVPs) for color-coded TDI were recorded in the ventricular septum and LV posterior wall before and after treatment. Peak myocardial velocities and peak myocardial velocity gradients (MVGs) in the LV walls were determined during systole and early diastole. The plasma concentration of transforming growth factor (TGF)-beta1 also was measured in all patients. Blood pressure and plasma TGF-beta1 level decreased after initiation of losartan therapy. The LV mass index and LV meridional end-systolic wall stress also decreased after treatment with losartan. LV geometry changed from a pattern consistent with concentric hypertrophy to normal geometry in 10 patients and to a pattern consistent with concentric remodeling in 5 patients, and from concentric remodeling to normal geometry in 5 patients after treatment with losartan. The ratio of early to late diastolic filling for the transmitral flow velocity increased after losartan treatment. The peak systolic and early diastolic myocardial velocities and MVGs in the ventricular septum and LV posterior wall increased after treatment with losartan, although the values 6 months after treatment with losartan were still lower than those in normal individuals. There were good correlations between changes in plasma TGF-beta1 level and changes in systolic and early diastolic MVGs 6 months after losartan. However, there were no significant correlations between changes in the systolic blood pressure and LV end-systolic wall stress and changes in the TDI parameters. CONCLUSION: Losartan improves regional LV function in patients with hypertension. Our newly developed averaged MVP and MVG measurements may be useful for accurately evaluating regional LV myocardial contractility and relaxation in these patients.
Angiology. 2004 Nov;55(6):669-678.
Zakynthinos E, Pierutsakos C, Konstantinidis K, Zakynthinos S, Papadogiannis D.
Department of Critical Care and Pulmonary Services, University of Athens Medical School, ``Evangelismos'' Hospital, Athens, Greece.
Losartan Reduces Left Ventricular Hypertrophy Proportionally to Blood Pressure Reduction in Hypertensives, but Does Not Affect Diastolic Cardiac Function.
Left ventricular hypertrophy proportionally to blood pressure reduction in patients with hypertension can be reduced by losartan with out affecting diastolic cardiac function. In contrast to the well-recognized salutary effects of angiotensin-converting enzyme inhibition, the value of angiotensin II type I (ATl)-receptor blockade on left ventricular hypertrophy (LVH) is controversial. In addition, the data on the influence of this therapy on cardiac diastolic function are scarce. Thirty-nine patients with moderate primary hypertension, LVH, and normal systolic function received losartan, 50 to 100 mg daily. Transthoracic echocardiography was performed at baseline and after 6 months of treatment. Thirty-one patients completed and were included in the study (16 males, 61.1 +/- .0 years). The patients were divided into responders if mean blood pressure (BP) decreased > 5 mm Hg at the end of the study (20 patients) and non-responders (mean BP decrease
Circulation. 2004 Nov 29.
Koh KK, Quon MJ, Han SH, Chung WJ, Ahn JY, Seo YH, Kang MH, Ahn TH, Choi IS, Shin EK.
Cardiology, Laboratory Medicine, and Endocrinology, Gachon Medical School, Incheon, Korea, and Diabetes Unit, Laboratory of Clinical Investigation, NCCAM, NIH, Bethesda, Md.
Additive Beneficial Effects of Losartan Combined With Simvastatin in the Treatment of Hypercholesterolemic, Hypertensive Patients.
Efficacy of Losartan co-administered with simvastatin in the treatment of hypercholesterolemic in patients with hypertension. BACKGROUND: Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in hypercholesterolemic, hypertensive patients. METHODS AND RESULTS: This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20 mg and placebo, simvastatin 20 mg and losartan 100 mg, or losartan 100 mg and placebo daily during each 2-month treatment period. Losartan alone or combined therapy significantly reduced blood pressure compared with simvastatin alone. Compared with losartan alone, simvastatin alone or combined therapy significantly changed lipoproteins. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and decreased plasma malondialdehyde and monocyte chemoattractant protein-1 levels relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy compared with simvastatin or losartan alone (both P<0.001 and P=0.030 for monocyte chemoattractant protein-1 by ANOVA). Combined therapy or losartan alone significantly increased plasma adiponectin levels and insulin sensitivity (determined by QUICKI) relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone (P<0.001 for adiponectin, P=0.029 for QUICKI by ANOVA). CONCLUSIONS: Simvastatin combined with losartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypercholesterolemic, hypertensive patients.
Int J Pharm. 2005 Mar 3;291(1-2):127-37. Epub 2004 Dec 28.
Lusina M, Cindric T, Tomaic J, Peko M, Pozaic L, Musulin N.
PLIVA-Research Institute Ltd., Analytics, Prilaz baruna Filipovica 29, 10000 Zagreb, Croatia.
Stability study of losartan/hydrochlorothiazide tablets.
A detailed study on the stability of losartan/hydrochlorothiazide tablets. The purpose of stability testing is to investigate how the quality of a drug product changes with time under the influence of environmental factors, to establish a shelf life for the product and to recommend storage conditions. Stability study of losartan/hydrochlorothiazide tablets is presented in this paper. Losartan (angiotensin II receptor antagonist) and hydrochlorothiazide (diuretic) are successfully used in association in the treatment of hypertension. Stability study of losartan/hydrochlorothiazide tablets consisted of three steps: stress test (forced degradation study), preliminary testing (selection of packaging) and formal stability testing. The results of stress test suggested that losartan/hydrochlorothiazide tablets are sensitive to moisture. It was demonstrated that the developed analytical methods are stability indicating. Additional preliminary testing was performed in order to select appropriate packaging for losartan/hydrochlorothiazide tablets. OPA/Al/PVC//Al blisters were found to provide adequate protection for the product. Based on the first 12 months of the formal stability study, a shelf life of 24 months was proposed. Losartan/hydrochlorothiazide tablets in OPA/Al/PVC//Al blisters are demonstrated to be chemically, physically and microbiologically stable.
Hypertens Res. 2004 Dec;27(12):963-70.
Horita Y, Tadokoro M, Taura K, Suyama N, Taguchi T, Miyazaki M, Kohno S.
Department of Internal Medicine, Nagasaki Municipal Medical Center.
Low-dose combination therapy with temocapril and losartan reduces proteinuria in normotensive patients with immunoglobulin a nephropathy.
Proteinuria in normotensive on immunoglobulin a nephropathy patients can be reduced by low-dose combination therapy with temocapril and losartan. This study investigates the ability of low doses of angiotensin-converting-enzyme inhibitors, in combination with angiotensin II receptor blockers, to exert antiproteinuric effects in normotensive and proteinuric outpatients with immunoglobulin A (IgA) nephropathy confirmed by biopsy. We performed a prospective, randomized, 6-month study of the effects of temocapril 1 mg (n =10), losartan 12.5 mg (n =10), and both (n =11) on mild-to-moderate proteinuria 0.76+/-0.35 g/day (range, 0.4 to 1.6 g/day) and renal function. The study subjects comprised 31 normotensive and proteinuric outpatients with IgA nephropathy accompanied by normal, or mild-to-moderately reduced but stable renal function (glomerular filtration rate>50 ml/min) without steroid or immunosuppressive therapy. We prospectively evaluated blood pressure, proteinuria, renal function and biochemical parameters before and after 6 months of therapy. The combination therapy significantly reduced proteinuria (63.2%) compared with either temocapril or losartan alone (41.3% and 36.6%, respectively, p =0.04 and 0.01, respectively). Blood pressure was most decreased in the group that received combination therapy. The reduced proteinuria did not correlate with reduced systolic or diastolic blood pressure or mean arterial pressure in any of the groups. The glomerular filtration rate fell during the first 3 months of combined therapy, but became reversible after a further 3 months of therapy. The combination significantly decreased angiotensin II (p <0.01), and this decrease was greater than that by either drug alone. In conclusion, the effectiveness of the combined therapy may have been at least partly due to the greater inhibition of the action of angiotensin II in patients with IgA nephropathy. This strategy apparently reduced mild-to-moderate proteinuria in patients with normotensive IgA nephropathy. (Hypertens Res 2004; 27: 963-970).
Cardiovasc Diabetol. 2005 May 15;4(1):6
Vitale C, Mercuro G, Castiglioni C, Cornoldi A, Tulli A, Fini M, Volterrani M, Rosano GM.
Metabolic Effect of Telmisartan and Losartan in Hypertensive Patients with Metabolic Syndrome.
Use of telmisartan and losartan in patients hypertension and metabolic syndrome and its effects. BACKGROUND: Metabolic syndrome is a cluster of common cardiovascular risk factors that includes hypertension and insulin resistance. Hypertension and diabetes mellitus are frequent comorbidities and, like metabolic syndrome, increase the risk of cardiovascular events. Telmisartan, an antihypertensive agent with evidence of partial peroxisome proliferator-activated receptor activity-gamma (PPARy) activity, may improve insulin sensitivity and lipid profile in patients with metabolic syndrome. METHODS: In a double-blind, parallel-group, randomized study, patients with World Health Organization criteria for metabolic syndrome received the highest Italian-licensing approved once-daily doses of telmisartan (80 mg, n = 20) or losartan (50 mg, n = 20) for 3 months. At baseline and end of treatment, fasting and postprandial plasma glucose, insulin sensitivity, glycosylated haemoglobin (HBA1c) and 24-hour mean systolic and diastolic blood pressures were determined. RESULTS: Telmisartan, but not losartan, significantly (p < 0.05) reduced free plasma glucose, free plasma insulin, homeostasis model assessment of insulin resistance and HbAic. Following treatment, plasma glucose and insulin were reduced during the oral glucose tolerance test by telmisartan, but not by losartan. Telmisartan also significantly reduced 24-hour mean systolic blood pressure (p < 0.05) and diastolic blood pressure (p < 0.05) compared with losartan. CONCLUSIONS: As well as providing superior 24-hour blood pressure control, telmisartan, unlike losartan, displayed insulin-sensitizing activity, which may be explained by its partial PPARy activity.
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