Carvedilol does not alter the insulin sensitivity in patients with congestive heart failure

This article provides information and a commentary on landmark trials presented at the American Heart Association meeting held in November 2004, relevant to the pathophysiology, prevention, and treatment of heart failure. An open trial of the ACORN Cardiac Support Device (CSD) showed encouraging preliminary results in patients with severe heart failure. The PEACE (Prevention of Events with Angiotensin-Converting Enzyme inhibition) study supports data from previous studies showing that ACE inhibitors reduce vascular events in patients at increased risk. The CREATE (clinical trial of metabolic modulation in acute MI treatment evaluation) study of patients with acute myocardial infarction (MI) showed no mortality benefit of a glucose/insulin/potassium regimen, but treatment with reviparin reduced the incidence of death, MI, or stroke. Azimilide was not associated with a significant reduction in shocks, but reduced the shocks or episodes of markedly symptomatic ventricular tachycardia terminated by pacing in the SHIELD (Shock Inhibition Evaluation with Azimilide) study. The addition of isosorbide dinitrate plus hydralazine to standard therapy improved survival in black heart failure patients in the A-HeFT (AfricanAmerican Heart Failure Trial) study. In an investigation of hypertensive patients with diabetes, carvedilol had fewer adverse effects on diabetic control than metoprolol. A meta-analysis of high-dose vitamin E supplementation suggested an association with increased mortality. The ESCAPE (Evaluation Study of CHF and Pulmonary Artery Catheterisation Effectiveness) study showed no benefit of pulmonary artery catheterisation over clinical management in patients with severe heart failure. Routine prophylactic coronary revascularisation for stable coronary disease prior to major vascular surgery showed no benefit in the CARP (Coronary Artery Revascularization Prophylaxis) study. Analysis of data from SCD-HeFT supports the cost-effectiveness of ICDs in heart failure, although overall cost implications may be prohibitive.

Section: Gemini: Glycemic Effects In Diabetes Mellitus: Carvedilolsupporting

confidence: 68%

Clinical trials update from the American Heart Association meeting: ACORN‐CSD, primary care trial of chronic disease management, PEACE, CREATE, SHIELD, A‐HeFT, GEMINI, vitamin E meta‐analysis, ESCAPE, CARP, and SCD‐HeFT cost‐effectiveness study

Shelton

Velavan

Nikitin

et al. 2005

“…A number of studies assessing the effect of carvedilol and doxazosin on glucose uptake in hypertension and in CHF patients with or without diabetes found no effect on insulin sensitivity. 23,24 Others, however, have reported an improvement in glycaemic control. 25 In a COMET substudy, comparing the effects of metoprolol and carvedilol on pre-existing and new onset diabetes in patients with CHF, researchers found that new onset diabetes is more likely to occur during treatment with metoprolol than during treatment with carvedilol.…”

Section: Discussionmentioning

confidence: 99%

Alpha‐receptor blockade improves muscle perfusion and glucose uptake in heart failure

Gomes

Mulder

Bellersen³

et al. 2010

AimsAlpha-adrenergic receptor-mediated vasoconstriction might underlie the insulin resistance seen in conditions associated with increased sympathetic tone, like chronic heart failure (CHF). Alpha-adrenergic receptor blockade by phentolamine could improve forearm blood flow (FBF) and forearm glucose uptake (FGU) in CHF patients. Methods and resultsIn 8 CHF patients and in 12 healthy volunteers, FBF (plethysmography) and FGU were measured in both forearms during a 150 min hyperinsulinaemic euglycaemic clamp procedure. During the final 30 min of the clamp, phentolamine was infused into one arm (experimental arm) at a dose of 5.0 mg; min 21 dL 21 of forearm volume. Insulin infusion (t ¼ 0-120 min) increased FGU in the two groups, without affecting FBF. In the CHF group, a-adrenergic receptor blockade by phentolamine (t ¼ 120-150 min) further increased FGU in the experimental arm from 3.0 + 0.7 to 5.0 + 0.9 mmol min 21 dL 21 (P ¼ 0.03). Forearm glucose uptake in the contralateral forearm remained unchanged. In the control group, phentolamine infusion did not increase FGU in the experimental forearm. The increase in blood flow in response to phentolamine was similar in both groups (CHF: 2.1 + 0.3-7.5 + 1.7 mL min 21 dL 21 , P , 0.001; controls 1.5 + 0.2 -5.5 + 0.8 mL min 21 dL 21 , P , 0.001 for both, CHF vs.control, P ¼ 0.2). Phentolamine did not affect FBF in the control arm in either group. ConclusionAlpha-adrenergic receptor blockade improves FGU in CHF patients. As the increase in FBF is similar in controls and CHF patients, this might be explained by an improved glucose-extraction capacity in CHF patients.--

“…However, the administration of β‐blockers to patients with concomitant diabetes has been questioned, because they may worsen insulin sensitivity and cause more severe hypoglycemic attacks [15,16]. In contrast to the traditional β‐blockers, carvedilol, because of its associated properties, has been shown not to affect plasma glucose levels and insulin sensitivity in hypertensive patients with concomitant diabetes mellitus, [17,18] and in patients with chronic heart failure [19]. In addition, β‐blockers might specifically counteract many of the untoward effects of diabetes mellitus, like myocardial ischemia, metabolic abnormalities or reduced vagal drive.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and tolerability of the long‐term administration of carvedilol in patients with chronic heart failure with and without concomitant diabetes mellitus

Nodari

Metra

Dei

et al. 2003

Background: Diabetes is frequently associated with heart failure and is an independent risk factor for an increased mortality and morbidity. Beta-blockers are traditionally regarded as relatively contraindicated in patients with diabetes mellitus. Aim of the study: To assess the efficacy and tolerability of carvedilol administration in patients with heart failure and concomitant diabetes. Methods and results: One hundred ninety-three patients (68 diabetics, 125 non-diabetics) with chronic heart failure were assessed by radionuclide ventriculography, cardiopulmonary exercise testing and right heart catheterization before and after 12 months of maintenance carvedilol treatment (mean dose, 40"19 mg daily). Diabetic patients were older and with a lower peak VO , 2 compared with non-diabetics. Long-term carvedilol administration was associated with an improvement in left ventricular function, clinical symptoms, resting and exercise hemodynamic parameters compared to baseline, with no significant difference between the diabetic and the non-diabetic patients. The incidence of adverse effects was also similar between the two groups. Diabetics had higher all-cause mortality with a similar mortality and hospitalization rate, compared to non-diabetics during 33"20 months of follow-up. Conclusion: Concomitant diabetes does not influence the efficacy and tolerability of carvedilol administration in patients with chronic heart failure.