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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ACE-inhibitors and AT, receptor antagonists play an important role in the treatment of cardiovascular and renal diseases. The criteria of evidence-based medicine indicate that ACE-inhibitors (in appropriate combinations with other cardiovascular agents) continue to represent the treatment of first choice in chronic heart failure, post-myocardial infarction with compromised ventricular function, high cardiovascular risk, and diabetic (type 1) nephropathy. It is here that the AT1 antagonists should be used--in particular when ACE-inhibitors are not tolerated. The AT1 antagonists, Irbesartan and Losartan, are applied, at appropriately high doses, primarily in hypertensives with diabetic (type 2) nephropathy. With the current exception of chronic heart failure, no confirmed data are yet available on the value of combination treatment. The LIFE study has shown that an AT1 antagonist is superior to an established beta blocker in hypertensives with an increased risk (left-ventricular hypertrophy), in particular when diabetes mellitus is impending or already present.
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PMID:[ACE inhibitor or AT1 antagonist. Is there a differential therapy?]. 1213 23

Irbesartan (SR 47436; BMS-186295) is a selective non-peptide antagonist of angiotensin II type 1 receptor (AT1). Irbesartan inhibits the action of angiotensin II, which acts through the binding to the AT1 receptor. Many experimental and clinical data show that activation of AT1 receptors plays the crucial role in the development of hypertension, hypertrophy of left ventricle, progression of lipid disorders and impairment of renal function. Therefore, the pharmacological intervention with angiotensin II type 1 receptor antagonists could be used as a new therapeutic option in treatment of hypertension and its complications. The advantage of irbesartan is its long lasting blood pressure lowering action and the possibility of taking it once a day. The principle of its action is not only limited to blocking the AT1 receptor, but it also participates in many other reactions of the renin-angiotensin-aldosterone system. According to the reports published, irbesartan and other antagonists of angiotensin II type 1 receptor seem to be a promising complement in the treatment of idiopathic hypertension, especially in patients with heart failure, diabetes and impaired renal function. Several studies showed that in addition to its long blood pressure lowering action (study of Pool, Fogari, Stumlple, Minran)--(possibility of taking the drug once a day), the AT1 antagonists reduced proteinuria (Sica et al.) without decreasing the creatinine clearance, improved the function of endothelium and inhibited the mitogen and proliferative action of angiotensin II on cardio-vascular system (Kahan et al., Tonkon et al., SILVER and ELITE trail).
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PMID:[Irbesartan--antihypertensive treatment in patients with heart failure and diabetes mellitus]. 1218 30

During the past few years, several major intervention trials have been conducted in an attempt to determine the efficacy of specific antihypertensive agents in retarding progression of diabetic nephropathy. These studies have clearly demonstrated the importance of renin-angiotensin system blockade in attenuating progressive renal disease. The preferred initial therapy is an angiotensin-converting enzyme (ACE) inhibitor, or an angiotensin type I (AT1) receptor antagonist based on the recent 'landmark' proof-of-concept trials--the Irbesartan Type 2 Diabetic Nephropathy Trial (IDNT) and the Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan (RENAAL). However, these clinical trials also demonstrate that aggressive blood pressure targets are needed in patients with diabetes and hypertension. This frequently requires multiple-drug therapy with several different classes of antihypertensive agents. Data from several clinical trials, including RENAAL, suggest that calcium antagonists may be added to ACE inhibitor or AT1 receptor antagonist therapy as needed to achieve target blood pressure. Calcium antagonists could, therefore, constitute an important component of the antihypertensive regimen in the management of patients with diabetic nephropathy.
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PMID:Evolving therapeutic strategies for retarding progression of diabetic nephropathy--an update for 2002. 1222 27

Diabetes mellitus is the most common cause of end-stage renal disease in the United States, accounting for about 50% of all new cases. Although we previously established the renoprotective benefits of angiotensin converting enzyme (ACE) inhibitors in patients with coexisting hypertension and type 1 diabetes, evidence of the renoprotective effect of ACE inhibitors in patients with type 2 diabetes is less clear. We conducted the Irbesartan Diabetic Nephropathy Trial (IDNT) to determine whether the angiotensin II receptor blocker (ARB) irbesartan slows the progression of nephropathy in patients with type 2 diabetes independently of its blood pressure (BP)-lowering effect. In this randomized, controlled trial, we found that irbesartan was associated with a 20% reduction in the risk for the primary composite end point (doubling of the baseline serum creatinine concentration, development of end-stage renal disease, or death from any cause) compared with placebo (P =.02) and a 23% reduction compared with amlodipine therapy (P =.006). These results were not explained by differences in the BP that was achieved. In a separate study, losartan was shown to reduce the risk for progression of renal disease in patients with type 2 diabetic nephropathy. Angiotensin II receptor blocker therapy has also been demonstrated to slow the progression to overt nephropathy when initiated early in the course of type 2 diabetic renal disease (ie, in patients with microalbuminuria). Based on these studies, ARBs are clearly effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection is independent of their BP-lowering effect. Preclinical studies with the newest ARB, olmesartan medoxomil, suggest that this agent may provide renoprotective benefits as well.
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PMID:The role of angiotensin II receptor blockers in preventing the progression of renal disease in patients with type 2 diabetes. 1238 93

In this article, 2 leading physicians debate the strength of outcome data on the efficacy of angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs) for reducing the incidence of cardiovascular, cerebrovascular, and renovascular events. Dr. Stephen G. Ball notes that the efficacy of ACE inhibitors for reducing the risk for myocardial infarction independent of their effects on blood pressure is controversial. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril treatment in high-risk patients was associated with a 20% reduction in the risk for myocardial infarction; mean reduction in blood pressure was 3 mm Hg for systolic blood pressure and 1 mm Hg for diastolic blood pressure. The HOPE investigators propose that the 20% reduction was much greater than would be expected based on the observed blood pressure reduction. However, a meta-regression analysis of blood pressure reduction in >20 antihypertensive therapy outcome trials found that the reduction in myocardial infarction risk with ramipril observed in HOPE was consistent with the modest blood pressure reduction seen with that agent. Nevertheless, there are convincing data for prevention of myocardial infarction with ACE inhibitors in patients with heart failure, including those with heart failure after myocardial infarction, as well as supportive evidence from studies in patients with diabetes mellitus and concomitant hypertension. On the other hand, Dr. William B. White takes the position that ARBs are well-tolerated antihypertensive agents that specifically antagonize the angiotensin II type 1 (AT(1)) receptor and provide a more complete block of the pathologic effects of angiotensin II-which are mediated via the AT(1) receptor-than ACE inhibitors. The Evaluation of Losartan in the Elderly (ELITE) II study and the Valsartan Heart Failure Trial (ValHeFT) suggest that ARBs reduce the risk for mortality in patients with congestive heart failure. The Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension trial also demonstrated beneficial effects of ARBs in the prevention of stroke events. The Irbesartan in Patients with Diabetes and Microalbuminuria (IRMA) study, the Irbesartan Diabetic Nephropathy Trial (IDNT), and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated significant reductions in the rate of progression of renal disease in patients receiving ARBs, independent of effects on blood pressure. These data support the use of ARBs, in addition to the standard of care, in hypertensive patients with heart failure who are intolerant of ACE inhibitors, and also provide compelling evidence for their use in patients with hypertension and type 2 diabetes.
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PMID:Debate: angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers--a gap in evidence-based medicine. 1451 6

Type 2 diabetes is an ever-growing problem worldwide. Approximately 40% of the patients with type 2 diabetes will develop diabetic kidney disease. In the United States, diabetes has become the most common single cause of endstage renal disease defined by the need for dialysis or transplantation. Patients with type 2 diabetes and diabetic nephropathy have a dramatically increased cardiovascular risk. The Irbesartan Diabetic Nephropathy Trial was designed to determine whether the use of irbesartan or a calcium channel blocker would provide protection against the progression of nephropathy due to type 2 diabetes beyond that attributable to the lowering of blood pressure. In that study, 1715 hypertensive patients with nephropathy due to type 2 diabetes were randomly assigned to irbesartan 300 mg/day or amlodipine 10 mg/day, or placebo. All patients randomized in this trial had more than 900 mg of protein in their urine and serum creatinines between 1.0 mg/dl and 3.0 mg/dl. The target blood pressure was 135/85 mmHg or less in all groups. The primary outcome was time to a combined endpoint of doubling of their baseline serum creatinine concentration, the development of endstage renal disease, or death from any cause. The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite endpoint that was 20% lower than that in the placebo group ( P = 0.02) and 23% lower than that in the amlodipine group ( P = 0.006). The risk of doubling of the serum creatinine concentration was 33% lower in the irbesartan group than in the placebo group ( P = 0.003) and 37% lower in the irbesartan group than in the amlodipine group ( P < 0.001). Treatment with irbesartan was associated with a relative risk of endstage renal disease that was 23% lower than that in both other groups. These differences were not accounted for by differences in the blood pressures that were achieved. Proteinuria was reduced on average by 33% in the irbesartan group as compared with 6% in the amlodipine group and 10% in the placebo group. The angiotensin II receptor blocker irbesartan was shown to be effective in protecting against the progression of nephropathy due to type 2 diabetes. In a study done in patients with type 2 diabetes and early nephropathy as manifested by microalbuminuria, 590 hypertensive patients with type 2 diabetes and microalbuminuria were randomized to receive either irbesartan 150 mg/day or irbesartan 300 mg/day and followed for 2 years. The primary outcome in that trial was the time to the onset of diabetic nephropathy, defined by persistent albuminuria in overnight specimens, with a urinary albumin excretion rate that was more than 200 mg/min or at least 30% higher than the baseline level. The irbesartan 150 mg/day group demonstrated a 39% relative risk reduction versus the control group in the development of overt proteinuria. The irbesartan 300 mg/day group demonstrated a highly significant 70% risk reduction versus the control group ( P < 0.001). The albumin excretion rate was reduced in the two irbesartan groups throughout the study (-11% and -38% at 24 months compared with baseline in the irbesartan 150-mg and 300-mg groups, respectively). The albumin excretion rate remained unchanged in the control group. Irbesartan was demonstrated in the above study to be renoprotective, independent of its blood pressure-lowering effect, in patients with type 2 diabetes and microalbuminuria. Thus, irbesartan, an angiotensin receptor blocker, was demonstrated to be significantly renoprotective in patients with type 2 diabetes with either early nephropathy (microalbuminuria) or late nephropathy (proteinuria). The renoprotective effects of irbesartan were above and beyond the effects irbesartan had on systemic blood pressure. Patients with type 2 diabetes and either early or late diabetic nephropathy should be treated with the angiotensin II receptor blocker irbesartan.
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PMID:Treatment of diabetic nephropathy with angiotensin II receptor antagonist. 1458 37

During the past decade, the incidence of end-stage renal disease (ESRD) has risen dramatically, primarily due to an increase in the incidence of diabetes. In patients with diabetes, both hyperglycemia and hypertension are independent risk factors for renal disease. Hypertension is also a risk factor in nondiabetic renal disease and contributes to renal dysfunction by increasing glomerular pressure, glomerular capillary damage, and proteinuria. The resultant nephron damage increases glomerular pressure and damage within remnant functional nephrons, further contributing to deterioration of renal function. In addition to its role in systemic hypertension, angiotensin II has direct effects on the kidney through elevation of glomerular capillary pressure and upregulation of components of the renal injury response. These direct effects of angiotensin II on the kidney support the inclusion of agents that target the renin-angiotensin system (RAS) into treatment regimens for patients at risk for renal disease. Several clinical trials have established the benefits of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in patients with diabetes. The ACE inhibitors have been shown to delay renal decline in patients with type 1 diabetes, whereas the renoprotective effect of these agents in patients with type 2 diabetes is less clear. The ARBs have been shown to provide significant benefits in patients with type 2 diabetes, both at early (microalbuminuria) and late (proteinuria) stages of renal decline. In the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, ARB therapy significantly reduced the progression of overt nephropathy (composite of doubling of serum creatinine, ESRD, and death), a benefit that has not been shown for ACE inhibitors. Moreover, in RENAAL, losartan significantly reduced the incidence of the individual end point of ESRD. The benefits of ARB therapy in IDNT and RENAAL were associated with significant reductions in proteinuria and were independent of blood pressure reductions. In RENAAL, proteinuria was a strong predictor of both renal and cardiovascular events. These findings underscore the importance of RAS blockade as a strategy for improving clinical outcomes in patients with renal disease.
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PMID:Recommendations for the management of special populations: renal disease in diabetes. 1462 61

Irbesartan is a long-acting angiotensin II antagonist acting specifically at the level of the Type 1-receptor subtype (AT1-receptor). This compound lowers blood pressure dose-dependently in hypertensive patients and has a placebo-like tolerability. The antihypertensive efficacy of irbesartan is greatly enhanced by the coadministration of a diuretic, and fixed-dose combinations of irbesartan and hydrochlorothiazide are now available. Irbesartan-based treatment appears especially effective for high-risk patients, such as those with diabetes, renal disease and cardiac hypertrophy. In patients with Type 2 diabetes, irbesartan delays the development of nephropathy as well as the progression of renal failure. Irbesartan may have antiatherosclerotic properties beyond those expected from blood pressure lowering per se: this AT1-blocker decreases the vascular oxidative stress and prevents the procoagulant as well as the pro-inflammatory effects of angiotensin II. Irbesartan given alone or in combination with a diuretic therefore represents a rational approach to treat hypertensive patients.
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PMID:AT1-receptor antagonism in hypertension: what has been learned with irbesartan? 1503 Feb 94

There are substantial healthcare costs associated with the provision of renal replacement therapy. Patients with diabetes mellitus are the largest and fastest growing group developing end-stage renal disease (ESRD) in the United Kingdom (UK). Treatment leading to a slowing of progression to ESRD in diabetic patients could lead to considerable cost savings. Using treatment-specific probabilities derived from the Irbesartan in Diabetic Nephropathy Trial (IDNT), the cost effectiveness of treating patients with hypertension, type II diabetes and nephropathy with irbesartan, amlodipine or control was calculated using a Markov model. UK-specific ESRD-related data were retrieved from published sources to reflect local management practices, ESRD outcomes and costs. Mean 10-year costs and changes in life expectancy due to ESRD delayed or avoided were calculated. Future costs and clinical benefits were discounted at 6.0 and 1.5% per annum and extensive sensitivity analyses were performed. Delay in the onset of ESRD with irbesartan led to cost savings of pound sterling 5125 and pound sterling 2919/patient and improvements in projected discounted life expectancy of 0.07 and 0.21 years over 10 years vs amlodipine and control, respectively. The costs of treatment of ESRD were the main contributor to the total costs. The cost of trial medications had only a minor impact. These results were robust in a wide range of plausible assumptions. Given that the IDNT efficacy results could be translated to a UK setting, treating patients with hypertension, type II diabetes and overt nephropathy with irbesartan was cost saving over a 10-year period compared to amlodipine and control.
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PMID:An economic evaluation of the Irbesartan in Diabetic Nephropathy Trial (IDNT) in a UK setting. 1511 42

Type 2 diabetes is increasing globally and is a major cause of conditions such as cardiovascular disease, retinopathy and nephropathy. The Diabetes Control and Complications Trial and the UK Prospective Diabetes Study demonstrated that the progression of renal disease could be slowed by tight glycaemic control and treating any associated hypertension with angiotensin-converting enzyme inhibition. 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 United States and Europe. The objective of this review is to demonstrate how results from the Program for Irbesartan Mortality and morbidity Evaluation studies apply to clinical practice, and to show how the benefits of irbesartan therapy can be realised at any stage of renal disease in patients with diabetes.
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PMID:What is the impact of PRIME on real-life diabetic nephropathy? 1511 95


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