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1.
Association of Sacubitril/Valsartan with Metabolic Parameters in Patients with Reduced Ejection Fraction Heart Failure at a Multidisciplinary Clinic.
Ryu, R, Tran, H, Bahjri, K
Metabolic syndrome and related disorders. 2021;(2):115-118
Abstract
Background: Sacubitril/valsartan was approved for New York Heart Association (NYHA) class II-IV heart failure with reduced ejection fraction (HFrEF) in 2015, based on the results of the PARADIGM-HF trial, which showed a reduction in cardiovascular (CV) death and heart failure hospitalization, compared with enalapril. A subsequent subgroup analysis of the trial showed glycemic improvement for patients on sacubitril/valsartan compared with those on enalapril. Methods: This was a retrospective observational study at the Loma Linda University (LLU) International Heart Institute (IHI). The aim was to evaluate the association of sacubitril/valsartan with glycemic index and other metabolic parameters, including change in hemoglobin A1C (HbA1C), blood pressure (BP), ejection fraction (EF), body weight, and lipid profile from baseline and at 3, 6, and 12 months. The rates of CV-related hospitalizations and total hospitalizations were also assessed. Results: The change in mean HbA1C from baseline was not significantly different at 1 year (P = 0.993). The mean EF was significantly higher and the mean diastolic BP was significantly lowered. Body weight and lipid parameters remained unchanged. Both the rates of CV-related hospitalizations and total hospitalizations were significantly lowered. For the prespecified subgroup analysis of diabetic HFrEF patients, the mean HbA1C was nonsignificant at 12 months (mean difference -0.48, P = 0.993). Conclusion: A non-significant reduction in HbA1C was associated in HFrEF patients with diabetes mellitus. Large randomized trials are needed to confirm our findings regarding the potential metabolic benefits of sacubitril/valsartan.
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2.
Comparative efficacy and safety of aliskiren and irbesartan in patients with hypertension and metabolic syndrome.
Krone, W, Hanefeld, M, Meyer, HF, Jung, T, Bartlett, M, Yeh, CM, Rajman, I, Prescott, MF, Dole, WP
Journal of human hypertension. 2011;(3):186-95
Abstract
Metabolic syndrome, a cluster of risk factors that increase the risk of cardiovascular morbidity and mortality, is common in patients with hypertension. Chronic renin-angiotensin-aldosterone system (RAAS) activation, shown by elevated plasma renin activity (PRA), is implicated in many of the features of metabolic syndrome. The direct renin inhibitor aliskiren may be of benefit in this patient group as aliskiren targets the RAAS at the rate-limiting step. In this double-blind study, 141 patients with hypertension (mean baseline BP 155/93 mm Hg) and metabolic syndrome (modified National Cholesterol Education Program ATP III criteria) were randomized to aliskiren 300 mg or irbesartan 300 mg once daily. Patients treated with aliskiren 300 mg had their mean sitting blood pressure (BP) lowered by 13.8/7.1 mm Hg after 12 weeks, significantly greater (P≤0.001) than the 5.8/2.8 mm Hg reduction observed in patients treated with irbesartan 300 mg. A significantly greater proportion of patients treated with aliskiren achieved BP control to <135/85 mm Hg (29.2 vs 16.7% with irbesartan; P=0.019). Aliskiren treatment led to a 60% decrease in PRA from baseline, whereas irbesartan increased PRA by 99% (both P<0.001). Aliskiren and irbesartan had similar effects on glucose and lipid profiles and on a panel of biomarkers of inflammation and cardiovascular risk. Both aliskiren and irbesartan were well tolerated. Collectively, these results suggest that aliskiren 300 mg may offer treatment benefits compared with irbesartan 300 mg for BP reduction in patients with hypertension and metabolic syndrome.
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3.
The value of irbesartan in the management of hypertension.
Bramlage, P, Durand-Zaleski, I, Desai, N, Pirk, O, Hacker, C
Expert opinion on pharmacotherapy. 2009;(11):1817-31
Abstract
Elevated blood pressure levels are highly prevalent and are a major reason for cardiovascular events and thus place a significant financial burden on healthcare systems worldwide. Guidelines recommend five first-line anti-hypertensive drug classes, but compelling indications may indicate favoring one drug class over another. Angiotensin receptor blockers (ARBs) have demonstrated a blood pressure lowering efficacy which is at least comparable with other drug classes, including ACE inhibitors (ACE-I), beta-blockers, calcium channel blockers and diuretics. They have, in addition, a lower side effect profile than other drug classes and patients on ARBs are more persistent with therapy. Compelling indications for the use of ARBs are heart failure, post-myocardial infarction, diabetic nephropathy, proteinuria/microalbuminuria, left ventricular hypertrophy, atrial fibrillation, metabolic syndrome and ACE-I induced cough. The ARB irbesartan has demonstrated a high efficacy in lowering blood pressure, which has been shown to be at least comparable with ACE-Is and superior to other ARBs such as losartan and valsartan. This translated into a better cost-effectiveness for irbesartan than for valsartan and losartan in the treatment of hypertension. In addition, irbesartan has been shown to be effective in both early and late stage diabetic nephropathy. It has further demonstrated considerable cost savings over standard therapy including beta-blockers, diuretics and non-dihydropyridine calcium channel blockers at all stages of kidney disease. Based on efficacy data from the Irbesartan Diabetic Nephropathy Trial and Reduction of Endpoints in NIDDM (non insulin dependant diabetes melitis) with the Angiotensin II Antagonist Losartan Study, it has also demonstrated cost savings over losartan in late stage renal disease. While both losartan and irbesartan are registered for the treatment of late stage diabetic nephropathy, irbesartan is also registered for early stage diabetic nephropathy in the EU. In summary, the data from randomized clinical trials on the efficacy of antihypertensive drugs provides an indication of their real value to patients. In addition observational data from clinical practice and proven end-organ protection in diabetic nephropathy provides further evidence of the true value of irbesartan compared to other ARBs in the treatment of hypertension.
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4.
Effect of the angiotensin receptor blocker irbesartan on metabolic parameters in clinical practice: the DO-IT prospective observational study.
Parhofer, KG, Münzel, F, Krekler, M
Cardiovascular diabetology. 2007;:36
Abstract
AIMS: A number of intervention studies have shown that therapy with angiotensin receptor blockers, such as irbesartan, can improve metabolic parameters and reduce the incidence of diabetes mellitus. It is unknown whether this observation also holds true in routine clinical settings. METHODS We evaluated the effect of irbesartan (150 mg or 300 mg/d) together with or without hydrochlorothiazide (12.5 mg/d) in 3259 German patients. A total of 750 primary care physicians evaluated up to 5 subsequent patients with metabolic syndrome (58.9% diabetic), in whom irbesartan therapy was newly initiated (87%) or continued (13%). RESULTS Six months of irbesartan therapy decreased systolic blood pressure by 14% (157.4 +/- 14.7 vs. 135.0 +/- 10.7 mmHg) and diastolic blood pressure by 13% (92.9 +/- 9.2 vs. 80.8 +/- 6.8 mmHg). This was associated with a decrease in body weight (-2.3%), fasting glucose (-9.5%), HbA1c (-4.6%), LDL-cholesterol (-11%), triglycerides (-16%) and gamma-GT (-12%) and an increase in HDL-cholesterol (+5%). These changes were somewhat more pronounced in male than in female patients and in obese than in lean patients. Changes in glucose concentration and HbA1c were much more prominent in diabetic patients. CONCLUSION Irbesartan therapy improves metabolic parameters in routine clinical settings. Thus, our study confirms previously published results from large intervention trials and extends the findings to routine clinical practice.
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5.
The effects of irbesartan and telmisartan on metabolic parameters and blood pressure in obese, insulin resistant, hypertensive patients.
Negro, R, Formoso, G, Hassan, H
Journal of endocrinological investigation. 2006;(11):957-61
Abstract
Obesity, hypertension, dyslipidemia and glucose intolerance cluster in the insulin resistance syndrome. Angiotensin II receptor blockers (ARB) are able to reduce insulin resistance. Furthermore, among ARB, telmisartan displays the property of stimulating PPARgamma. The aim of the study was to examine if and to what extent treatment with irbesartan and telmisartan induces variations in metabolic parameters in insulin resistant, hypertensive subjects. Forty-six non diabetic, obese, insulin-resistant, hypertensive patients took part in the study. They were divided into 2 groups. Group A (23) was submitted to irbesartan 150 mg/day, Group B (23) to telmisartan 80 mg/day for 6 months. Adiponectin, glucose, cholesterol, triglycerides, free fatty acids (FFA), steady-state plasma insulin and glucose (SSPG), 24-hBP were determined at the beginning and at the end of the study. Both irbesartan or telmisartan reduced blood pressure and ameliorated the insulin sensitivity, with increased adiponectin values; in Group B, the amelioration of metabolic parameters was greater than in Group A and the reduction of blood pressure was related with variation of adiponectin levels. Data obtained showed that the antihypertensive action of telmisartan and irbesartan is associated with the amelioration of the metabolic picture. The greater impact on the improvement of the metabolic profile showed by telmisartan and the inverse correlation between adiponectin levels and blood pressure may be partly due to the action as partial PPARgamma agonist displayed by telmisartan.
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6.
Perspectives on prehypertension.
Nesbitt, SD
Journal of the cardiometabolic syndrome. 2006;(5):364-5
Abstract
The Trial of Preventing Hypertension (TROPHY) investigated pharmacologic intervention in patients with prehypertension. TROPHY confirmed that treatment with candesartan 16 mg can prevent or postpone the development of hypertension, demonstrating a 66.3% reduction in hypertension incidence relative to placebo (26.8% absolute reduction) at 2 years, and a 15.6% reduction in hypertension incidence relative to placebo (9.8% absolute reduction) at 4 years. Further analyses of TROPHY may help to delineate the mechanisms behind this result more specifically, including those relating to components of the metabolic syndrome and markers of inflammation and early vascular change. The rate of progression and the concurrence of risk factors make a strong case for the development of a directive for closer follow-up and treatment. The potential for success in reducing cardiovascular events is great, given the prevalence of prehypertension and the likelihood of progression.
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7.
Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-alpha.
Derosa, G, Cicero, AF, D'Angelo, A, Ragonesi, PD, Ciccarelli, L, Piccinni, MN, Pricolo, F, Salvadeo, SA, Ferrari, I, Gravina, A, et al
Hypertension research : official journal of the Japanese Society of Hypertension. 2006;(11):849-56
Abstract
The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56+/-5, treated with telmisartan; and 45 males and 48 females, aged 55+/-4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-alpha (TNF-alpha), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbAlc and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-alpha and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes.
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8.
Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study.
Sola, S, Mir, MQ, Cheema, FA, Khan-Merchant, N, Menon, RG, Parthasarathy, S, Khan, BV
Circulation. 2005;(3):343-8
Abstract
BACKGROUND The metabolic syndrome is associated with increased angiotensin II activity, induction of a proinflammatory and oxidative state, and endothelial dysfunction. We evaluated the ability of irbesartan, an angiotensin receptor blocker, and lipoic acid, an antioxidant, to affect endothelial function and inflammation in patients with the metabolic syndrome. METHODS AND RESULTS We randomized 58 subjects with the metabolic syndrome in a double-blinded manner to irbesartan 150 mg/d (n=14), lipoic acid 300 mg/d (n=15), both irbesartan and lipoic acid (n=15), or matching placebo (n=14) for 4 weeks. Endothelium-dependent and -independent flow-mediated vasodilation was determined under standard conditions. Plasma levels of interleukin-6, plasminogen activator-1, and 8-isoprostane were measured. After 4 weeks of therapy, endothelium-dependent flow-mediated vasodilation of the brachial artery was increased by 67%, 44%, and 75% in the irbesartan, lipoic acid, and irbesartan plus lipoic acid groups, respectively, compared with the placebo group. Treatment with irbesartan and/or lipoic acid was associated with statistically significant reductions in plasma levels of interleukin-6 and plasminogen activator-1. In addition, treatment with irbesartan or irbesartan plus lipoic acid decreased 8-isoprostane levels. No significant changes in blood pressure were noted in any of the study groups. CONCLUSIONS Administration of irbesartan and/or lipoic acid to patients with the metabolic syndrome improves endothelial function and reduces proinflammatory markers, factors that are implicated in the pathogenesis of atherosclerosis.