The Experts below are selected from a list of 10935 Experts worldwide ranked by ideXlab platform
Stefan Peters - One of the best experts on this subject based on the ideXlab platform.
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Can Angiotensin Receptor Antagonists Prevent Restenosis After Stent Placement?
American Journal of Cardiovascular Drugs, 2002Co-Authors: Stefan PetersAbstract:Restenosis rates after coronary stent implantation in complex lesions are between 30 and 50%. Neointimal hyperplasia promoted by complex interaction between cellular and acellular elements, such as cytokines and growth factors, is thought to be the primary process responsible for restenosis. The risk of in-stent restenosis is increased in patients with a history of restenosis after percutaneous transluminal coronary angioplasty, in long lesions, in total occlusions, in patients with diabetes mellitus, in small vessels, in the proximal parts of the left anterior descending coronary artery and in cases of stent oversizing. In-stent restenosis represents a serious economic burden on society because treatment strategies include expensive approaches such as cutting-balloon angioplasty, rotational atherectomy and brachytherapy. A number of pharmacological agents, including ACE inhibitors, have been unsuccessful in preventing restenosis. Alternative procedures such as brachytherapy, radioactive stents and drug-eluting stents are under evaluation. Although sirolimus- or paclitaxel-eluting stents have been associated with very low restenosis rates over durations of 6 to 12 months, the long-term efficacy and tolerability of this approach is currently being investigated. Although ACE inhibitors have failed in reducing restenosis rates, the selective Angiotensin II type 1 (AT_1) Receptor Antagonist valsartan has shown encouraging results in the single-center Valsartan for Prevention of Restenosis after Stenting of Type B2/C lesions trial (ValPREST). The ValPREST trial is the first randomized, placebo-controlled study to have evaluated the effect of an Angiotensin Receptor Antagonist on in-stent restenosis in a moderate number of patients. Compared with ACE inhibitors, Angiotensin Receptor blockers exert additional effects on the pathophysiological processes which lead to restenosis. Angiotensin Receptor Antagonists may affect several mechanisms involved in neointimal hyperplasia such as decreasing circulating cytokine and growth factor levels and reducing neutrophil activation, especially after stenting in acute coronary syndromes, but the results need to be confirmed in a large multicenter trial. The question whether long-term therapy, with an oral Angiotensin Receptor Antagonist, is cost-effective and whether Angiotensin Receptor Antagonists should be used as an add-on therapy to drug-eluting stents, requires clarification.
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Can Angiotensin Receptor Antagonists Prevent Restenosis After Stent Placement?
American Journal of Cardiovascular Drugs, 2002Co-Authors: Stefan PetersAbstract:Restenosis rates after coronary stent implantation in complex lesions are between 30 and 50%. Neointimal hyperplasia promoted by complex interaction between cellular and acellular elements, such as cytokines and growth factors, is thought to be the primary process responsible for restenosis. The risk of in-stent restenosis is increased in patients with a history of restenosis after percutaneous transluminal coronary angioplasty, in long lesions, in total occlusions, in patients with diabetes mellitus, in small vessels, in the proximal parts of the left anterior descending coronary artery and in cases of stent oversizing. In-stent restenosis represents a serious economic burden on society because treatment strategies include expensive approaches such as cutting-balloon angioplasty, rotational atherectomy and brachytherapy. A number of pharmacological agents, including ACE inhibitors, have been unsuccessful in preventing restenosis. Alternative procedures such as brachytherapy, radioactive stents and drug-eluting stents are under evaluation. Although sirolimus- or paclitaxel-eluting stents have been associated with very low restenosis rates over durations of 6 to 12 months, the long-term efficacy and tolerability of this approach is currently being investigated. Although ACE inhibitors have failed in reducing restenosis rates, the selective Angiotensin II type 1 (AT_1) Receptor Antagonist valsartan has shown encouraging results in the single-center Valsartan for Prevention of Restenosis after Stenting of Type B2/C lesions trial (ValPREST). The ValPREST trial is the first randomized, placebo-controlled study to have evaluated the effect of an Angiotensin Receptor Antagonist on in-stent restenosis in a moderate number of patients. Compared with ACE inhibitors, Angiotensin Receptor blockers exert additional effects on the pathophysiological processes which lead to restenosis. Angiotensin Receptor Antagonists may affect several mechanisms involved in neointimal hyperplasia such as decreasing circulating cytokine and growth factor levels and reducing neutrophil activation, especially after stenting in acute coronary syndromes, but the results need to be confirmed in a large multicenter trial. The question whether long-term therapy, with an oral Angiotensin Receptor Antagonist, is cost-effective and whether Angiotensin Receptor Antagonists should be used as an add-on therapy to drug-eluting stents, requires clarification.
Arthur M Feldman - One of the best experts on this subject based on the ideXlab platform.
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An Opportunity to Definitively Evaluate the Theoretical Risks of Neprilysin Inhibition
JACC. Heart failure, 2017Co-Authors: Arthur M FeldmanAbstract:Solomon et al. [(1)][1] recently described the rationale and design of a trial aimed at identifying the potential utility of the combination of the Angiotensin Receptor Antagonist valsartan and the neprilysin inhibitor sacubitril (Entresto) for the treatment of individuals with heart failure and
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Neprilysin Inhibition in the Time of Precision Medicine.
JACC. Heart failure, 2016Co-Authors: Arthur M FeldmanAbstract:The recent results of the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) showing that the combination of the neprilysin (NEP) inhibitor sacubitril (sac) and the Angiotensin Receptor Antagonist (ARB) valsartan (
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valsartan sacubitril for heart failure reconciling disparities between preclinical and clinical investigations
JAMA, 2016Co-Authors: Arthur M Feldman, Julia A Haller, Steven T DekoskyAbstract:Valsartan/sacubitril (Entresto, Novartis) is a combination of the neprilysin inhibitor sacubitril and the Angiotensin Receptor Antagonist valsartan. In July 2015, the US Food and Drug Administration (FDA) approved valsartan/sacubitril through the fast-track pathway for the treatment of patients with New York Heart Association class II through IV heart failure symptoms and a reduced ejection fraction. The approval was based on the results of a single phase 3 clinical trial (PARADIGM-HF)1 that included 8400 patients. In this trial, valsartan/sacubitril was associated with a 20% (hazard ratio, 0.80) decrease in the primary end point of death from cardiovascular cause or first hospitalization for heart failure (from 26.5% to 21.8%), when compared with the Angiotensin-converting inhibitor enalapril, and a 16% (hazard ratio, 0.84) reduction in all-cause mortality (from 19.8% to 17.0%). However, recent translational science studies involving the central nervous system and the eye suggest that other effects of valsartan/sacubitril might influence its use in some patients.
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Valsartan/Sacubitril for Heart Failure: Reconciling Disparities Between Preclinical and Clinical Investigations.
JAMA, 2016Co-Authors: Arthur M Feldman, Julia A Haller, Steven T DekoskyAbstract:Valsartan/sacubitril (Entresto, Novartis) is a combination of the neprilysin inhibitor sacubitril and the Angiotensin Receptor Antagonist valsartan. In July 2015, the US Food and Drug Administration (FDA) approved valsartan/sacubitril through the fast-track pathway for the treatment of patients with New York Heart Association class II through IV heart failure symptoms and a reduced ejection fraction. The approval was based on the results of a single phase 3 clinical trial (PARADIGM-HF)1 that included 8400 patients. In this trial, valsartan/sacubitril was associated with a 20% (hazard ratio, 0.80) decrease in the primary end point of death from cardiovascular cause or first hospitalization for heart failure (from 26.5% to 21.8%), when compared with the Angiotensin-converting inhibitor enalapril, and a 16% (hazard ratio, 0.84) reduction in all-cause mortality (from 19.8% to 17.0%). However, recent translational science studies involving the central nervous system and the eye suggest that other effects of valsartan/sacubitril might influence its use in some patients.
Itamar Raz - One of the best experts on this subject based on the ideXlab platform.
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The Role of Sulodexide in the Treatment of Diabetic Nephropathy
Drugs, 2007Co-Authors: Ram Weiss, Robert Niecestro, Itamar RazAbstract:Diabetic nephropathy is an important cause of morbidity and mortality in patients with either type 1 or type 2 diabetes mellitus. The pathogenesis and natural history of diabetic nephropathy, characterised by a progressive decline in glomerular function, were initially described in patients with type 1 diabetes. Reports that describe the glomerulopathy and progression of renal disease in patients with type 2 diabetes suggest that the disease process is similar to that observed in patients with type 1 diabetes with diabetic nephropathy. An emerging body of evidence supports the notion that glomerular capillary wall and mesangial alterations in diabetic nephropathy involve pathobiochemical alterations of glycoproteins in these structures. Evidence in experimental animals rendered diabetic, reveal that the administration of heparin and other anionic glycoproteins can effectively prevent the biochemical alterations that promote albuminuria. Clinical reports of the use of sulodexide, a preparation of low molecular weight glycosaminoglycan polysaccharides, have shown that proteinuria is significantly diminished in patients with diabetic nephropathy, even when these patients are receiving either an ACE inhibitor or Angiotensin Receptor Antagonist.
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renoprotective effect of the Angiotensin Receptor Antagonist irbesartan in patients with nephropathy due to type 2 diabetes
The New England Journal of Medicine, 2001Co-Authors: Edmond J Lewis, Lawrence G Hunsicker, William R Clarke, Tomas Berl, Marc A Pohl, Julia B Lewis, Eberhard Ritz, Robert C Atkins, Richard D Rohde, Itamar RazAbstract:Background It is unknown whether either the Angiotensin-II–Receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure. Methods We randomly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan (300 mg daily), amlodipine (10 mg daily), or placebo. The target blood pressure was 135/85 mm Hg or less in all groups. We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration, the development of end-stage renal disease, or death from any cause. We also compared them with regard to the time to a secondary, cardiovascular composite end point. Results The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo gro...
Adrienne A.m. Zandbergen - One of the best experts on this subject based on the ideXlab platform.
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Short-term administration of an Angiotensin-Receptor Antagonist in patients with impaired fasting glucose improves insulin sensitivity and increases free IGF-I
European journal of endocrinology, 2006Co-Authors: Adrienne A.m. Zandbergen, Steven W. J. Lamberts, Joop A.m.j.l. Janssen, Aart H. BootsmaAbstract:Objective: Blocking the renin–Angiotensin system (RAS) may reduce the risk of developing type-2 diabetes, but data are inconclusive and the mechanisms involved are unclear. RAS and RAS inhibition also influence the IGF-I system, which is important in glucose homeostasis. We investigated the effects of the Angiotensin-Receptor Antagonist, losartan, on insulin resistance and IGF-I levels Design and methods: In this hypothesis-generating study, five individuals with impaired fasting glucose received 100 mg losartan during 8 weeks. Before and after the treatment period, insulin sensitivity was assessed using the homeostasis model assessment of insulin resistance (HOMA), as well as the 2-h continuous infusion of glucose with model assessment (CIGMA). Furthermore, serum levels of free and total IGF-I, IGF-binding protein-3 (IGFBP-3), lipids and HbAlc were measured. Results: After the treatment period, the HOMA score for insulin resistance had decreased from 5.3G1.1 to 3.7G0.9 (PZ0.004) and the 2-h CIGMA score from 23.4G3.1 to 15.9G2.1 (PZ0.07). The serum levels of free IGF-I had increased from 57G18.8 to 134G31.3 pmol/l (PZ0.04). In terms of percentage, the decrease of HOMA correlated with the increase in free IGF-I levels (Pearson’s correlation coefficient rZK0.8; PZ0.07). A trend in the same direction was observed with 2-h CIGMA. No differences were observed in lipids, total IGF-I, IGFBP-3 or HbAlc. Conclusions: Losartan raised serum levels of free IGF-I, which might contribute to the improvement of insulin resistance associated with losartan treatment. These observations, if confirmed in broader studies, will help our understanding of the pathogenesis of type-2 diabetes mellitus, as well as the role of Angiotensin-Receptor Antagonists in its prevention.
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Effect of Losartan on Microalbuminuria in Normotensive Patients with Type 2 Diabetes Mellitus
Annals of Internal Medicine, 2003Co-Authors: Adrienne A.m. Zandbergen, Steven W. J. Lamberts, Aart H. Bootsma, Marinus G.a. Baggen, Dick De Zeeuw, Rob J.th. OuwendijkAbstract:The Angiotensin-Receptor Antagonist losartan reduces urinary albumin excretion in normotensive patients with type 2 diabetes and microalbuminuria. The effect of losartan on proteinuria is independe...
Aart H. Bootsma - One of the best experts on this subject based on the ideXlab platform.
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Short-term administration of an Angiotensin-Receptor Antagonist in patients with impaired fasting glucose improves insulin sensitivity and increases free IGF-I
European journal of endocrinology, 2006Co-Authors: Adrienne A.m. Zandbergen, Steven W. J. Lamberts, Joop A.m.j.l. Janssen, Aart H. BootsmaAbstract:Objective: Blocking the renin–Angiotensin system (RAS) may reduce the risk of developing type-2 diabetes, but data are inconclusive and the mechanisms involved are unclear. RAS and RAS inhibition also influence the IGF-I system, which is important in glucose homeostasis. We investigated the effects of the Angiotensin-Receptor Antagonist, losartan, on insulin resistance and IGF-I levels Design and methods: In this hypothesis-generating study, five individuals with impaired fasting glucose received 100 mg losartan during 8 weeks. Before and after the treatment period, insulin sensitivity was assessed using the homeostasis model assessment of insulin resistance (HOMA), as well as the 2-h continuous infusion of glucose with model assessment (CIGMA). Furthermore, serum levels of free and total IGF-I, IGF-binding protein-3 (IGFBP-3), lipids and HbAlc were measured. Results: After the treatment period, the HOMA score for insulin resistance had decreased from 5.3G1.1 to 3.7G0.9 (PZ0.004) and the 2-h CIGMA score from 23.4G3.1 to 15.9G2.1 (PZ0.07). The serum levels of free IGF-I had increased from 57G18.8 to 134G31.3 pmol/l (PZ0.04). In terms of percentage, the decrease of HOMA correlated with the increase in free IGF-I levels (Pearson’s correlation coefficient rZK0.8; PZ0.07). A trend in the same direction was observed with 2-h CIGMA. No differences were observed in lipids, total IGF-I, IGFBP-3 or HbAlc. Conclusions: Losartan raised serum levels of free IGF-I, which might contribute to the improvement of insulin resistance associated with losartan treatment. These observations, if confirmed in broader studies, will help our understanding of the pathogenesis of type-2 diabetes mellitus, as well as the role of Angiotensin-Receptor Antagonists in its prevention.
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Effect of Losartan on Microalbuminuria in Normotensive Patients with Type 2 Diabetes Mellitus
Annals of Internal Medicine, 2003Co-Authors: Adrienne A.m. Zandbergen, Steven W. J. Lamberts, Aart H. Bootsma, Marinus G.a. Baggen, Dick De Zeeuw, Rob J.th. OuwendijkAbstract:The Angiotensin-Receptor Antagonist losartan reduces urinary albumin excretion in normotensive patients with type 2 diabetes and microalbuminuria. The effect of losartan on proteinuria is independe...