Cardiovasc Diabetol.
2005 May 15;4(1):6
Metabolic Effect of Telmisartan and Losartan in Hypertensive Patients
with Metabolic Syndrome.
Vitale C, Mercuro G, Castiglioni C, Cornoldi A, Tulli A, Fini
M, Volterrani M, Rosano GM.
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.
Hypertens Res. 2004 Dec;27(12):963-70.
Low-dose combination therapy with temocapril and losartan reduces
proteinuria in normotensive patients with immunoglobulin a nephropathy.
Horita Y, Tadokoro M, Taura K, Suyama N, Taguchi T, Miyazaki
M, Kohno S.
Department of Internal Medicine, Nagasaki Municipal Medical Center.
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).
Int J Pharm. 2005 Mar 3;291(1-2):127-37. Epub 2004 Dec 28.
Stability study of losartan/hydrochlorothiazide tablets.
Lusina M, Cindric T, Tomaic J, Peko M, Pozaic L, Musulin N.
PLIVA-Research Institute Ltd., Analytics, Prilaz baruna Filipovica 29,
10000 Zagreb, Croatia.
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.
Circulation. 2004 Nov 29.
Additive Beneficial Effects of Losartan Combined With Simvastatin
in the Treatment of Hypercholesterolemic, Hypertensive Patients.
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.
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.
Angiology. 2004 Nov;55(6):669-678.
Losartan Reduces Left Ventricular Hypertrophy Proportionally to
Blood Pressure Reduction in Hypertensives, but Does Not Affect Diastolic
Cardiac Function.
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. ezakynth@yahoo.com.
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 </= 5 mm Hg, 11 patients). The BP and the LVH were significantly reduced (systolic BP by 10.0%, diastolic BP 6.5%, mean BP 8.2%, left ventricular mass index [LVMI] 6.2%, interventricular septum 5.8%, posterior wall 3.0%) (p</=0.02), attributed to the reduction of BP and LVH in responders; the LVH in non-responders did not alter with treatment. A significant correlation was noted between changes in BP and LVMI (r=0.60, p<0.001). The systolic cardiac function remained normal. The Doppler parameters usually used to assess the diastolic function of the LV (early diastolic filling velocity [E wave], late diastolic filling velocity [A wave], ratio of E/A waves, isovolumic relaxation time), which were abnormal at baseline, did not change with treatment. The size of the left atrium increased (p<0.05) at the end of the study. In conclusion, a 6-month course with losartan decreased BP and LVH. However, the LVH regression was rather associated with the reduction of the hemodynamic stimulus per se, than any trophic effect of the drug in the myocardium. The diastolic cardiac function remained abnormal with treatment.
J Card Fail. 2004 Oct;10(5):412-20.
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.
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.
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.
Drugs Today (Barc). 2004 Sep;40(9):791-801.
Stroke prevention with losartan in the context of other antihypertensive
drugs.
Chrysant SG.
University of Oklahoma School of Medicine and Oklahoma Cardiovascular
and Hypertension Center, Oklahoma City, Oklahoma 73132, USA. schrysant@yahoo.com
Several large clinical trials have demonstrated that successful control of blood pressure decreases the incidence of strokes. Also, drugs that stimulate the production of angiotensin II, such as diuretics, calcium channel blockers (CCBs) and angiotensin receptor blockers (ARBs), provide additional stroke reduction than drugs that suppress angiotensin II production such as beta-blockers and angiotensin converting enzyme (ACE) inhibitors. Since the stroke-protective effect of angiotensin II is mediated through stimulation of the AT2 receptors, drugs that selectively block the AT1, such as the ARBs, provide greater stroke protection than the other antihypertensive drugs. The blockade of the AT1 receptors lessens local brain ischemia, whereas the stimulation of the AT2 receptors increases local blood flow through recruitment of collateral vessels. Among the ARBs, losartan possesses certain unique properties not shared by other members of its class, which enhance its stroke-protective effects. These include the prevention of platelet adhesiveness and aggregation and the decrease of serum uric acid levels, which both lead to reduction in cardiovascular and cerebrovascular events. ( (c) 2004 Prous Science.
Am J Nephrol. 2004 Nov 3;24(5):543-548
Effects of Combination Treatment with Losartan and Trandolapril
on Office and Ambulatory Blood Pressures in Non-Diabetic Renal Disease:
A COOPERATE-ABP Substudy.
Nakao N, Seno H, Kasuga H, Toriyama T, Kawahara H, Fukagawa M.
Kaikou-Kai Central Clinic, Division Nephrology, Nagaya Kyoritsu Hospital,
Nagoy, Japan.
Background: In the COOPERATE trial, the combination treatment of the angiotensin-II receptor blocker losartan and the angiotensin-converting-enzyme inhibitor trandolapril significantly retarded progression of non-diabetic kidney disease compared with each monotherapy. The benefit could be greatly attributable to the potent reduction of proteinuria, because the three treatment groups showed the same reductions of office blood pressure (OBP). Ambulatory blood pressure (ABP) is reported to be better than OBP in predicting progression of kidney disease. Methods: Ninety-two patients enrolled in the COOPERATE trial underwent 24-hour ABP monitoring at randomization and at month 6, year 1, year 2 and year 3 on randomized treatment. Results: Both OBP and ABP were similarly reduced among the three groups at all measurement points (p = NS) and throughout the whole study period (p = NS). No significant correlation between the change in 24-hour ABP and the change in proteinuria was seen (p = NS). A Cox-multivariable analysis showed that covariates affecting the renal outcomes (a doubling serum-Cr level and/or end-stage renal failure) were the change in proteinuria (hazard ratio 0.49, 95% CI 0.34-0.78, p = 0.01) and treatments (0.58, 0.45-0.99, 0.03), but not 24-hour ABP (0.98, 0.89-2.01, 0.17). Conclusion: The better renoprotective effect of the combination treatment is attributed to BP-independent mechanisms by more complete renin-angiotensin system blockade. Copyright (c) 2004 S. Karger AG, Basel.
Acta Crystallogr C. 2004 Nov 15;60(Pt 11):o821-o823. Epub 2004 Oct 22.
Trityl losartan.
Sieron L, Nagaraj B, Prabhuswamy B, Yathirajan HS, Nagaraja P,
Narasegowda RS, Gaonkar SL.
Institute of General and Ecological Chemistry, Technical University of
Lodz, Zeromskiego 116, 90-924 Lodz, Poland.
The title compound (systematic name: {2-butyl-4-chloro-1-[2'-(2-trityl-2H-tetrazol-5-yl)biphenyl-4-ylmethyl]-1H-imidazol-5-yl}methanol), C(41)H(37)ClN(6)O, crystallizes in the centrosymmetric space group P-1 with two independent molecules in the asymmetric unit. These molecules differ significantly only in the relative orientations of the rings in the biphenylyltetrazole moieties. One of the molecules shows disorder for three C atoms in the n-butyl group. Hydrogen bonds link the molecules in an infinite chain along the a axis.
Curr Opin Ophthalmol. 2004 Dec;15(6):508-18.
Pharmacotherapy for diabetic retinopathy.
Comer GM, Ciulla TA.
Department of Ophthalmology, Indiana University School of Medicine, Indianapolis,
Indiana, USA, and Vitreoretinal Service, Midwest Eye Institute, Indianapolis,
Indiana, USA.
PURPOSE OF REVIEW: Diabetic retinopathy (DR) is a potentially visually devastating complication of chronic hyperglycemia and other associated systemic abnormalities. Numerous large, prospective, randomized clinical trials have delineated the current standard prevention and treatment protocols including intensive glycemic and blood pressure control and laser photocoagulation for neovascularization and clinically significant macular edema. However, despite standard intervention, vision loss from DR still occurs at an alarming rate. Thus, more recently, researchers have directed their efforts towards better understanding the microscopic changes occurring in DR to develop more effective pharmacologic prevention and treatment strategies. RECENT FINDINGS: Phase II and III clinical studies involving antivascular endothelial growth factor (VEGF) and protein kinase C (PKC) inhibitors for the management of diabetic macular edema are underway. Researchers recently found elevated pigment endothelium-derived factor (PEDF) associated with active neovascularization, a finding that counteracts prior claims of endogenous anti-angiogenic properties. Other clinical trials are underway to evaluate the efficacy of octreotide, celecoxib, and candesartan on DR. Small clinical studies have suggested beneficial treatment effects for triamcinolone acetonide, interferon alpha-2a, and supplemental oxygen; however, other studies involving losartan, vitamins C and E, and atorvastatin failed to show any benefit. SUMMARY: Over the past decade, numerous animal models have led to a more thorough understanding of the early microvascular alterations and later neovascularization and edema observed in DR. These discoveries and subsequent human clinical studies involving direct and indirect growth factor modulation, extracellular matrix alteration, vitreolysis, and alternative DR pathways including dyslipidemia, hypoxia, and sorbitol are reviewed in this manuscript.
J Cardiovasc Pharmacol. 2004 Nov;44(5):520-4.
Effects of losartan and chlorthalidone on blood pressure and renal
vascular resistance index in non-diabetic patients with essential hypertension
and normal renal function.
Caruso D, D'Avino M, Acampora C, Romano L, Bevilacqua N, Caruso
G, Esposti DD, Borghi C.
12Unit of Internal Medicine, Cardarelli Hospital, Napoli, Italy.
Antihypertensive drugs can differ in target organ protection despite similar blood pressure (BP) control. We compared the effects of losartan (L) and chlorthalidone (C) on renal vascular resistance index (RVRI) in 194 grade I to II, non-diabetic hypertensive patients with increased RVRI (>0.68 m/s by echo-Doppler) but normal renal function. Patients were randomly allocated to C 25 mg/d or L 50 mg/d according to a single blind, PROBE study design. After 4 weeks of treatment, 92 patients (48 L/44 C) with BP <140/90 mm Hg were enrolled in the long-term phase of the study. After 12 months a normalization of RVRI was observed in 47 of 48 patients treated with L (97.5%) and only in 14 of 44 of those treated with C (25.8%) despite no differences in BP control. Patients whose RVRI remained elevated during C therapy underwent a 2-week washout period and then were treated with L 50 mg/d for 12 additional months. After that period 28 of 30 (95%) of patients who were nonresponders to C showed a normalization of RVRI despite no differences in BP control. In conclusion, our data suggest that treatment with L can improve renal hemodynamic and exert a protective renal effect beyond BP control in patients with hypertension.
Expert Opin Pharmacother. 2004 Nov;5(11):2311-20.
Losartan for the treatment of hypertension and left ventricular
hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension
(LIFE) study.
Devereux RB, Lyle PA; Losartan Intervention For Endpoint reduction
in hypertension study.
Weill Medical College of Cornell University, Division of Cardiology, Box
222, 525 East 68th Street, New York, NY 10021, USA. rbdevere@med.cornell.edu
Losartan is an orally active, selective, nonpeptide, angiotensin-II Type I-receptor antagonist, and was the first drug marketed in this class. It has been approved for the treatment of hypertension, and may be used alone or in combination with other antihypertensive agents. Based on the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, losartan has been approved for the reduction of cardiovascular events in patients with hypertension and left ventricular hypertrophy, but there is evidence that this benefit does not apply to black patients. Based on the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, losartan is also indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria, in patients with Type 2 diabetes. The focus of this review is the LIFE study.
Arzneimittelforschung. 2004 Sep;54(9a):611-7.
Combination of losartan and hydrochlorothiazide: in vivo bioequivalence.
Koytchev R, Ozalp Y, Erenmemisoglu A, van der Meer MJ, Alpan
RS.
Cooperative Clinical Drug Research and Development, Neuenhagen, Germany.
mail@ccdrdag.com
Two trials were performed in different groups of volunteers with the aim to compare the bioavailability of 50 mg losartan tablets (Sarvas as test and an originator product as reference formulation; study 1) and losartan/hydrochlorothiazide (50 mg/12.5 mg) (CAS 124750-99-8/CAS 58-93-5) combined formulations (Sarvastan as test and an originator product as reference formulation; study 2), respectively. Each study was conducted according to an open, randomized, single-dose, two-period cross-over design in 24 healthy volunteers with a wash-out period from 7 to 14 days. Blood samples were taken up to 36 h in the first study and up to 48 h in the second study. Concentrations of losartan and its principal active metabolite, i.e. E3174, as well as hydrochlorothiazide were determined by HPLC or LC-MS-MS, respectively. In the first study, the 90% confidence interval for intra-individual ratios of AUC0-t and Cmax of losartan were between 0.91 and 1.03 (AUC0-t) as well as between 0.87 and 1.19 (Cmax), and thus within the acceptance ranges. The 90% confidence interval for intra-individual ratios of AUC0-t, and Cmax of E3174 were between 0.90 and 1.13 for AUC0-t, and between 0.97 and 1.14 for Cmax. In the second study, i.e. after administration of combined losartan/hydrochlorothiazide formulations, the 90% confidence interval for intra-individual ratios of AUC0-t and Cmax of losartan were between 0.90 and 1.04 (AUC0-t) as well as between 0.86 and 1.20 (Cmax). Similarly to the parent compound, no significant differences of bioavailability parameters of E3174 between the two studied formulations were found. The 90% confidence interval for intra-individual ratios of AUC0-t and Cmax of hydrochlorothiazide were between 0.89 and 0.98 (AUC0-t) as well as between 0.82 and 1.00 (Cmax). In the light of the present studies it can be concluded that the losartan as well as losartan/hydrochlorothiazide test formulations are bioequivalent to the respective reference formulations.
Pediatr Int. 2004 Oct;46(5):576-9.
Combined therapy of enalapril and losartan attenuates histologic
progression in immunoglobulin A nephropathy.
Tanaka H, Suzuki K, Nakahata T, Tsugawa K, Konno Y, Tsuruga K,
Ito E, Waga S.
Department of Pediatrics, Hirosaki University School of Medicine, Hirosaki,
Japan. hirotana@cc.hirosaki-u.ac.jp
BACKGROUND: It has been reported that combined therapy of angiotensin converting enzyme inhibitor and angiotensin receptor blocker significantly decreases proteinuria in immunoglobulin A (IgA) nephropathy. However, histologic alterations following the therapy have not been reported. METHODS: A total of nine Japanese children with severe proteinuric IgA nephropathy who received a prompt immunosuppressive therapy were enrolled the study, four of whom received a combined therapy of angiotensin converting enzyme inhibitor, enalapril and angiotensin receptor blocker, losartan (Group A), while the remaining five did not (Group B). All underwent renal biopsy before and approximately 12 months after the first renal biopsy. RESULTS: At presentation, urine protein excretion and the histologic indices of mean activity index, mean chronicity index and tubulointerstitial scores did not show a statistical difference between the two groups: Group A (2.6 +/- 0.6 g/day; mean activity index, 5.0 +/- 1.0; mean chronicity index, 5.0 +/- 1.0; tubulointerstitial scores, 4.3 +/- 1.0) and Group B (2.2 +/- 0.6 g/day; mean activity index, 4.8 +/- 0.8; mean chronicity index, 4.8 +/- 1.3; tubulointerstitial scores, 3.6 +/- 0.5, respectively). All had normal blood pressure and renal function. Urine protein excretion and the activity index decreased at the second renal biopsy, while the chronicity index and the tubulointerstitial scores slightly increased or remained unchanged. In comparison with Group B, a significant suppression in increasing the chronicity index and the tubulointerstitial scores obtained at the second renal biopsy were observed in Group A [Group A: 4.3 +/- 1.2 and 3.0 +/- 0.0, respectively, vs Group B: 6.0 +/- 0.7 and 4.4 +/- 0.9, respectively (P < 0.05)]. One patient in Group B developed chronic renal insufficiency thereafter. CONCLUSIONS: Although only a small number of patients were examined, these clinical findings suggest that a combined therapy of enalapril and losartan may attenuate histologic progression in at least a proportion of patients with severe proteinuric IgA nephropathy.
Drugs. 2004;64(21):2399-416.
Management of acute and chronic gouty arthritis: present state-of-the-art.
Schlesinger N.
Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert
Wood Johnson Medical School, New Brunswick, New Jersey 08903-0019, USA.
schlesna@umdnj.edu
There are three stages in the management of gout: (i) treating the acute attack; (ii) lowering excess stores of uric acid to prevent flares of gouty arthritis and to prevent tissue deposition of urate; and (iii) providing prophylaxis to prevent acute flares. It is important to distinguish between therapy to reduce acute inflammation in acute gout and therapy to manage hyperuricaemia in patients with chronic gouty arthritis.During the acute gouty attack nonpharmacological treatments such as topical ice and rest of the inflamed joint are useful. NSAIDs are the preferred treatment in acute gout. The most important determinant of therapeutic success is not which NSAID is chosen, but rather how soon NSAID therapy is initiated. Other treatments include oral and intravenous colchicine, intra-articular and systemic corticosteroids, and intramuscular corticotropin.Optimal treatment of chronic gout requires long-standing reduction in serum uric acid. The urate-lowering drugs used to treat chronic gout are the uricosuric drugs, the uricostatic drugs, which are xanthine oxidase inhibitors, and the uricolytic drugs. Xanthine oxidase inhibitors such as allopurinol, oxipurinol and febuxastat should be used as first-line treatment in patients with renal calculi, renal insufficiency, concomitant diuretic therapy and ciclosporin (cyclosporine) therapy, and urate overproduction. Uricosuric drugs include probenecid, benzbromarone, micronised fenofibrate and losartan. They are the urate-lowering drugs of choice in allopurinol-allergic patients and underexcretors with normal renal function and no history of urolithiasis. The use of recombinant urate oxidase in patients with chronic gout is limited by the need for parenteral administration, the potential antigenicity and production of anti-urate oxidase antibodies, and declining efficacy.The effectiveness of colchicine prophylaxis as an isolated therapy is still to be confirmed by placebo-controlled trials. Another issue is prophylaxis with NSAIDs. There are no comparative studies with colchicine.
Swiss Med Wkly. 2004 Aug 7;134(31-32):440-7.
The cost-effectiveness of losartan in type 2 diabetics with nephropathy
in Switzerland--an analysis of the RENAAL study.
Szucs TD, Sandoz MS, Keusch GW.
Institute for Social-and Preventative Medicine, University of Zurich,
Switzerland.
BACKGROUND: The prevalence and incidence of diabetic nephropathy with endstage renal disease (ESRD) have increased globally over recent decades. Diabetic nephropathy with ESRD for type 2 diabetes mellitus (DM) now has to be recognized as a growing public health problem. Several studies have found that angiotensin-II receptor antagonists have a renoprotective effect in type 2 diabetics with diabetic nephropathy, independently of their antihypertensive effects. These studies have shown a prevention of the progression of nephropathy to ESRD, or a slowing of that progression. The RENAAL study demonstrated the clinical benefits of losartan in patients with DM type 2 and advanced diabetic nephropathy. AIM: The aim of this cost-effectiveness analysis of the RENAAL study was to evaluate the effect of losartan compared to a placebo from a Swiss third party payer perspective. METHODS: Using a decision analytic model, we evaluated the cost-effectiveness for losartan on the basis of the RENAAL study. A follow-up period of 3.5 years was used. Effectiveness was defined as the number of ESRD days saved. We valued haemodialysis, peritoneal dialysis and kidney transplantation. A weighted mean value was calculated for the daily costs of an ESRD (CHF 215.05). In the case of renal transplantation follow-on costs, resource utilization was determined through a telephone-based interview with 5 of the 6 Swiss transplantation centres. Expert consensus methodology was used to determine the proportion of health care resource utilization in type 2 diabetics. The percentage of patients receiving each of the 3 treatment alternatives was derived from a cross-sectional national study conceived for this purpose. The daily costs for haemodialysis and peritoneal dialysis were derived from figures provided by insurers. The costs of treatment with losartan were calculated on the basis of an average daily dose of losartan over a period of 3.5 years. RESULTS: Over a period of 3.5 years, losartan significantly reduced the number of ESRD days of type 2 diabetics with nephropathy by an average of 33.6 days (95% CI: 10.9, 56.3) compared to the placebo. This reduction in the number of ESRD days resulted in ESRD-associated cost savings of CHF 7,226 per patient over a period of 3.5 years (the ESRD-associated costs savings increased to CHF 10,086 per patient after 4 years). If the average costs per patient for treatment with losartan for the same period (CHF 3,142) are subtracted from the CHF 7,226 then the reduction in ESRD days yields net cost savings of CHF 4,084 per patient over 3.5 years. The univariate sensitivity analyses for the variables ESRD daily costs and percentage distribution of the 3 treatment modalities always yielded net cost savings. DISCUSSION: This evaluation revealed net cost savings of CHF 4,084 (F 2,687) for patients with diabetic nephropathy and type 2 diabetes when given 50 to 100 mg losartan once daily over a period of 3.5 years compared to placebo. The net cost savings that administration of losartan yielded are of considerable importance given that the annual costs of diabetic nephropathy with ESRD in type 2 diabetics in Switzerland are approximately CHF 46 million. On the basis of the scientific evidence currently available, the use of losartan to prevent the advance of diabetic nephropathy is worthwhile from both a clinical and economic perspective.
