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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two studies comparing the cost-effectiveness of irbesartan to similar blood pressure control with standard antihypertensive medications (excluding angiotensin-converting enzyme inhibitors and other angiotensin receptor blockers) in treatment of patients with hypertension, type 2 diabetes, and microalbuminuria have been published to date; one in a United States setting, the other in a Spanish setting. Both studies were based on a Markov-based Monte Carlo simulation model, with the effects of irbesartan or standard blood pressure control taken from the Irbesartan Reduction of Microalbuminuria-2 (IRMA-2) and the Irbesartan in Diabetic Nephropathy Trial (IDNT) clinical trials. In both Spanish and U.S. settings, irbesartan was projected to delay the onset of end-stage renal disease (ESRD), reduce the cumulative incidence of ESRD, increase life expectancy, and reduce overall direct medical costs. Irbesartan treatment of patients with type 2 diabetes, hypertension, and microalbuminuria may lead to major improvements in long-term patient outcomes, with substantial cost savings as an added bonus to third party payers.
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PMID:Health economics studies assessing irbesartan use in patients with hypertension, type 2 diabetes, and microalbuminuria. 1548 4

Individuals with type 2 diabetes and nephropathy represent a particularly high-risk group for both adverse cardiac as well as renal events. Using the Irbesartan in Diabetic Nephropathy Trial (IDNT) cohort, our objective was to determine baseline characteristics of individuals with type 2 diabetic nephropathy and hypertension predictive for cardiac events. IDNT identified 1715 individuals with type 2 diabetic nephropathy and hypertension having serum creatinine of 1.0 to 3.0 mg/dL and urinary albumin excretion rates > or = 900 mg/day. A cardiovascular (CV) composite was used consisting of CV death, nonfatal MI, hospitalization for heart failure, stroke, amputation, and coronary and peripheral revascularization. Using multivariable Cox regression analysis, 41 baseline characteristics determined a priori were analyzed for their potential relationship to risk of experiencing a CV event. Of the 1715 individuals, 518 (30.2%) had at least one of the CV composite end points. Older age, male gender, longer duration of diabetes, history of cardiovascular disease, history of CHF, high urinary albumin:creatinine ratio, and low serum albumin were strong predictors for CV events; of these, prior history of CVD (RR 2.00, 95% CI 1.63-2.45; P < 0.0001) and high urinary albumin:creatinine ratio (RR 1.29 per natural log unit, 95% CI 1.13-1.48; P = 0.0002) at baseline were highly predictive for cardiovascular events. In conclusion, among individuals with hypertension and diabetic nephropathy, both the degree of albuminuria and lower serum albumin levels provide additional prognostic information concerning cardiovascular risk, in addition to traditional coronary risk factors.
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PMID:Predictors of cardiovascular events in patients with type 2 diabetic nephropathy and hypertension: a case for albuminuria. 1548 18

Irbesartan (Aprovel) belongs into the new group drugs for the cardiovascular system which exert an antagonistic effect at the level of angiotensin II, but experimental pilot studies as well as clinical studies draw also attention to the possible therapeutic potential of AT1 receptor blockers in the treatment of chronic heart failure. Irbesartan has a marked antihypertensive effect as is apparent from a recent clinical study in 139 patients with mild and moderate hypertension--implemented in the Czech Republic. Twelve-week treatment with Irbesartan led to a marked drop of the systolic and diastolic blood pressure (159.2 +/- 14 vs. 137 +/- 13 mmHg/99.2 +/- 7 vs. 85.3 +/- 7 mmHg, p < 0.01). A very favourable therapeutic effect was recorded in this investigation also in 24-hour monitoring of the blood pressure. The use of irbesartan in patients with arterial hypertension has according to other studies also a favourable effect on organ complications of hypertension and diabetes (regression of left ventricular hypertrophy, reduction of albuminuria). Irbesartan may prove due to its favourable effect a suitable alternative in conditions associated with intolerance of ACE-inhibitors in patients with moderate and severe forms of arterial hypertension, in chronic heart failure and in diabetic nephropathy.
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PMID:[Irbesartan in the treatment of arterial hypertension]. 1564 39

Elevated arterial pressure enhances the risk for cardiovascular (CV) events in patients with diabetic nephropathy. The optimal BP and the component of the elevated BP that affect the risk have not been defined. A post hoc analysis was performed to assess the impact of achieved systolic, diastolic, and pulse pressures on CV outcomes in 1590 adults who had overt diabetic nephropathy and were enrolled in the Irbesartan Diabetic Nephropathy Trial (IDNT) and had a baseline serum creatinine above the normal range, up to 266 micromol/L (3.0 mg/dL), 24-h urine protein >900 mg/d, and at least 6 mo of follow-up. Patients were randomized to irbesartan, amlodipine, or placebo, with other antihypertensive agents to a BP goal of < or =135/85 mmHg. Progressively lower achieved systolic BP (SBP) to 120 mmHg predicted a decrease in CV mortality and congestive heart failure (CHF) but not myocardial infarctions (MI). A SBP below this threshold was associated with increased risk for CV deaths and CHF events. Achieved diastolic BP <85 mmHg was associated with a trend to increase in all-cause mortality, significant increase in MI, but decreased risk for strokes. Increased pulse pressure predicted increased all-cause mortality, CV mortality, MI, and CHF. It is concluded that achieved SBP approaching 120 mmHg and diastolic BP of 85 mmHg are associated with the best protection against CV events in these patients. BP < or =120/85 may be associated with an increase in CV events.
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PMID:Impact of achieved blood pressure on cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial. 1593 97

Aggressive treatment of hypertension is effective in reducing both microvascular and macrovascular complications in type 2 diabetes, with target BP < 130/80 mmHg being recommended. Angiotensin-converting enzyme inhibitors were found to be more effective than the other traditional agents in reducing the onset of clinical proteinuria in individuals with both type 1 and type 2 diabetes and incipient nephropathy. However, small trials on patients with type 2 diabetes and overt nephropathy failed to demonstrate a specific renoprotective role for this class of drugs. The aim of the Program for Irbesartan Mortality and Morbidity Evaluation was to ascertain whether angiotensin II receptor blockers are effective in both preventing the development of clinical proteinuria and delaying the progression of nephropathy in type 2 diabetes. The Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA) Study showed that, as compared with conventional therapy, irbesartan is better at preventing the development of clinical proteinuria and at restoring normoalbuminuria for comparable BP control in patients with incipient nephropathy. The Irbesartan Diabetic Nephropathy Trial showed that irbesartan is more effective than traditional antihypertensive therapies in reducing the progression toward ESRD in patients with type 2 diabetes and overt nephropathy regardless of changes in BP. Moreover, secondary analysis of the Irbesartan Diabetic Nephropathy Trial showed that the achieved systolic pressure as well as baseline and current proteinuria significantly predict renal outcomes. In conclusion, the results of the Program for Irbesartan Mortality and Morbidity Evaluation demonstrate that irbesartan significantly prevents the development of clinical proteinuria in individuals with microalbuminuria and delays the progression of nephropathy in individuals with proteinuria. Moreover, the renoprotective effects of irbesartan go beyond its effect on BP.
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PMID:Prevention and treatment of diabetic nephropathy: the program for irbesartan mortality and morbidity evaluation. 1593 34

Despite the introduction of new antihypertensive agents such as angiotensin-converting enzyme inhibitors and calcium channel antagonists, the blood pressure of fewer than 30% of hypertensive patients is controlled with current therapies; compliance and continuation with medication are poor. The renin-angiotensin system is important in the pathophysiology of hypertension, end-organ damage and congestive cardiac failure. Irbesartan is an angiotensin II receptor antagonist that provides dose-dependent, specific, insurmountable blockade of the AT1 receptor both in vivo and in vitro. It is rapidly absorbed after oral administration, has a bioavailability of 60-80% with no food effect, does not require metabolism to a bioactive compound, and is excreted by both biliary and renal routes so that dosage adjustments are unnecessary in patients with renal or hepatic disease. Irbesartan produces dose-dependent blood pressure reductions, with 24 h activity confirmed by ambulatory blood pressure monitoring. Irbesartan is effective in the elderly and non-elderly, men and women and in cases of mild and severe hypertension. The recommended starting dosage is 150 mg once daily (o.d.), which can be increased to 300 mg. Its antihypertensive effect is accentuated by diuretic co-administration. In controlled clinical trials, irbesartan was at least as effective as atenolol, hydrochlorothiazide, amlodipine and enalapril. In a double-blind study, irbesartan 300 mg was more effective than losartan 100 mg, and in a dose-titration study, irbesartan 150-300 mg produced significantly greater blood pressure reductions than losartan 50-100 mg. In pooled data from nine placebo-controlled studies, adverse event and discontinuation rates for irbesartan were similar to those for placebo, and there was no relationship between dose and adverse effects. Preliminary clinical data suggest positive haemodynamic effects in heart failure and renoprotective effects in diabetic nephropathy.
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PMID:Pharmacology of irbesartan. 1599 21

Hypertension is a powerful risk factor for cardiovascular (CV) morbidity and mortality; therefore, blood pressure (BP) lowering plays a central role in reducing the cardiovascular complications of hypertension, including stroke. Recent outcomes studies--Losartan Intervention For Endpoint reduction in hypertension, Reduction of Endpoints in Non-insulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan, and the Irbesartan Type 2 Diabetic Nephropathy Trial--suggest that some angiotensin II antagonists are associated with CV and renal effects beyond their ability to lower BP in patients with hypertension or diabetic nephropathy and may play a role in the prevention of new-onset type 2 diabetes. Angiotensin II antagonists are associated with a wide variety of vascular, cardiac, and renal effects, as well as molecule-specific effects independent of those induced by the angiotensin-I receptor. These actions may offer a mechanistic explanation for the outcome benefits observed in patients with hypertension or diabetic nephropathy. Angiotensin-converting enzyme inhibitors and calcium-channel blockers may also have effects that are not completely explained by differences in the antihypertensive response to these agents, but the evidence is less robust. Collectively, these findings suggest that management of patients with hypertension, with or without diabetes or renal disease, should no longer be viewed as simply a matter of correcting elevated BP. Antihypertensive agents that possess CV benefits beyond their BP-reducing effects should be used to prevent the development of end-organ damage.
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PMID:Do angiotensin II antagonists provide benefits beyond blood pressure reduction? 1602 Apr 2

Type 2 diabetes is a chief cause of pathologies such as cardiovascular disease, nephropathy and retinopathy, and its prevalence is increasing worldwide. Development of renal disease can be slowed by tight glycaemic control and treatment of associated hypertension with angiotensin-converting enzyme inhibition, as The Diabetes Control and Complications Trial and the UK Prospective Diabetes Study have demonstrated. Recent clinical trials have supported the use of angiotensin II receptor antagonists in the treatment of diabetic nephropathy, resulting in the approval of new therapeutic indications in the US and Europe. The main goal of this review is to demonstrate how results from the Programme for Irbesartan Mortality and Morbidity Evaluation and other recent studies, based on the effects of renin-angiotensin system blockade, can be appropriate in clinical practice, thus displaying benefits of irbesartan therapy at any stage of renal disease in diabetics.
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PMID:An update of irbesartan and renin-angiotensin system blockade in diabetic nephropathy. 1608 46

Elevated arterial pressure is a major risk factor for progression to ESRD in diabetic nephropathy. However, the component of arterial pressure and level of BP control for optimal renal outcomes are disputed. Data from 1590 hypertensive patients with type 2 diabetes in the Irbesartan Diabetic Nephropathy Trial (IDNT), a randomized, double-blind, placebo-controlled trial performed in 209 clinics worldwide, were examined, and the effects of baseline and mean follow-up systolic BP (SBP) and diastolic BP and the interaction of assigned study medications (irbesartan, amlodipine, and placebo) on progressive renal failure and all-cause mortality were assessed. Other antihypertensive agents were added to achieve predetermined BP goals. Entry criteria included elevated baseline serum creatinine concentration up to 266 micromol/L (3.0 mg/dl) and urine protein excretion >900 mg/d. Baseline BP averaged 159/87 +/- 20/11 mmHg. Median patient follow-up was 2.6 yr. Follow-up achieved SBP most strongly predicted renal outcomes. SBP >149 mmHg was associated with a 2.2-fold increase in the risk for doubling serum creatinine or ESRD compared with SBP <134 mmHg. Progressive lowering of SBP to 120 mmHg was associated with improved renal and patient survival, an effect independent of baseline renal function. Below this threshold, all-cause mortality increased. An additional renoprotective effect of irbesartan, independent of achieved SBP, was observed down to 120 mmHg. There was no correlation between diastolic BP and renal outcomes. We recommend a SBP target between 120 and 130 mmHg, in conjunction with blockade of the renin-angiotensin system, in patients with type 2 diabetic nephropathy.
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PMID:Independent and additive impact of blood pressure control and angiotensin II receptor blockade on renal outcomes in the irbesartan diabetic nephropathy trial: clinical implications and limitations. 1612 Aug 23

Proteinuria is a graded marker for kidney damage, as well as the risk for future cardiovascular events. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) reduce urinary protein excretion and slow progression of renal impairment, independent of blood pressure lowering. Both the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction in Endpoints in NIDDM with the Angiotensin Antagonist Losartan (RENAAL) study were large, randomized, prospective studies in type 2 diabetic patients with proteinuria. There was no reduction in the incidence of myocardial infarction or stroke with the ARBs compared to placebo in either trial. A broader overview of clinical trials comparing ACEIs and ARBs with other antihypertensive drugs fails to show any substantive blood pressure-independent effects on stroke or myocardial infarction with these classes of drugs. Therefore, for cardiovascular end points (as opposed to renal end points), it may be more important that the blood pressure is reduced, rather than how the process is started.
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PMID:Antihypertensive, antiproteinuric therapy and myocardial infarction and stroke prevention. 1615 81


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