Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In most, but not all, studies antihypertensive treatment with angiotensin converting enzyme inhibitors (ACE inhibitors) improves insulin sensitivity, whereas beta-blockers decrease insulin sensitivity. However, there was a significant increase in body weight with beta-blockers and changes in the body potassium homeostasis with ACE inhibitors. In order to compare the drug specific metabolic effects of an ACE inhibitor and a cardioselective beta-blocker controlling these factors, we measured insulin sensitivity in a randomized, double-blind cross-over study in 22 healthy volunteers (age 27 +/- 3 years; BMI 22.0 +/- 1.5 kg m-2 (mean +/- SD)) during euglycaemic glucose clamps before and after 4 weeks' administration of 5 mg Lisinopril or 5 mg Bisoprolol. Both drug phases were separated by 4 weeks of no drug administration. During the insulin sensitivity measurements potassium concentrations were clamped at basal levels by means of a variable i.v. potassium infusion. Body weight was monitored at weekly intervals and kept constant within +/- 1 kg of the subjects' baseline weight throughout the entire study period. Insulin sensitivity did not change significantly during either drug administration period. The insulin sensitivity index of the 22 volunteers after administration of the ACE inhibitor was 7.9 +/- 2.4 mL min-1 m2 microU-1 mL-1 (basal index 8.3 +/- 1.9 mL min-1 m2 microU-1 mL-1, and 7.5 +/- 2.1 mL min-1 m2 microU-1 mL-1 after administration of the beta-blocker (basal index 8.2 +/- 1.9 mL min-1 m2 microU-1 mL-1; NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Four week administration of an ACE inhibitor and a cardioselective beta-blocker in healthy volunteers: no influence on insulin sensitivity. 758 16

Recently, several randomised controlled studies have demonstrated improvement in survival of patients with non ischemic cardiomyopathy (Bisoprolol, Metoprolol, Carvedilol) and ischemic cardiomyopathy (Carvedilol). It is not quite clear, whether the observed difference in mortality after beta-blockade on top of diuretics, digitalis and ACE-inhibitors is due to some as yet unknown pathophysiological changes. Certainly, beta-blocking agents have an established efficacy in arrhythmia. Irrespective of the acknowledged benefit in survival, one should note, that the risk reduction in mortality by 65% by Carvedilol has to be viewed critically-as the risk reductions in several other large scale trials. If the mortality in the group receiving digitalis, diuretics and ACE-inhibitors was 7.8%, the mortality after addition of Carvedilol was 3.2%. This means a difference of 4.6%. If however, percent from percent is calculated, than the risk reduction amounts to 65%. One can easily understand, why this larger latter, number usually is being published.
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PMID:[Beta-blockers and heart failure--a critical view]. 908 82

Clinical research in chronic heart failure has recently focused on the stimulated neuro-hormonal compensatory mechanisms that could contribute to auto-aggravation of the disease. On the basis of such a hypothesis, and apart from the inhibition of the renin angiotensin system, the antagonism of beta-receptors has evolved as a promising approach for improving quality of life and prognosis. However, the definite proof of beta-adrenoceptor blockade induced benefit on survival remains to be demonstrated. On the basis of CIBIS I data, the objective of the Cardiac Insufficiency Bisoprolol Study II (CIBIS II) is to evaluate effects of the selective beta-1 adrenoceptor blocker, bisoprolol, on mortality (primary endpoint) in patients with ischaemic or non-ischaemic chronic heart failure. Eligible patients will be symptomatic ambulatory patients with left ventricular ejection fraction < or = 35% in NYHA functional class III or IV, receiving a background treatment of diuretics and angiotensin converting enzyme inhibitors. A total of 2,500 patients are planned to be included with a mean follow up of at least 3 years. Secondary endpoints include hospitalisations, cardiovascular mortality and combination of both as well as permanent treatment withdrawal. Bisoprolol will be titrated up to 10 mg, starting with 1.25 mg daily. Randomization began in November 1995. CIBIS II results will represent a basis for definite conclusions on the evaluation of beta-adrenoceptor blockade induced benefit with bisoprolol in chronic heart failure.
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PMID:Design of the cardiac insufficiency bisoprolol study II (CIBIS II). The CIBIS II Scientific Committee. 910 60

There is now considerable clinical trial data to support the use of beta-blockers in patients with congestive heart failure (CHF) due to systolic left ventricular dysfunction. A substantial database has accumulated over the last 20 years supporting the benefits of these agents on ventricular function and clinical status. In addition, morbidity and mortality benefits have been suggested, specifically with the non-selective vasodilating agent, carvedilol. More recently, a "new wave" of clinical trials have been conducted to definitively determine the mortality benefits of beta-blockers in patients with mild to moderate CHF as well as addressing other important clinical questions. These questions include whether the beneficial effects of carvedilol on survival can be reproduced by other agents in prospective, adequately powered studies; whether the benefits of carvedilol in systolic heart failure are due to its beta-blocking properties alone or to a combination of the beta-blocking and ancillary effects of the drug; whether beta-blockers are of benefit in patients with severe New York Heart Association (NYHA) Class IIIB-IV CHF; and, whether beta-blockers are of benefit (additional to ACE inhibitors) in patients with evidence of systolic ventricular dysfunction when commenced in the immediate post-myocardial infarction period. Major studies are currently being undertaken to address the above questions. Most are still underway but 3 studies have recently reported their results: the second Cardiac Insufficiency Bisoprolol Study (CIBIS II), the Research in Left Ventricular Dysfunction Study (RESOLVD), and the Metoprolol CR/XL Randomised Intervention Trial in Heart Failure (MERIT-HF) study. These studies have demonstrated that blockade with beta1-selective, non-vasodilating agents (i.e. bisoprolol and metoprolol) improve survival in patients with CHE Comparison of relative risk reduction in these recent studies with the earlier carvedilol studies raises mechanistic questions, specifically whether non-selectivity, vasodilation and other ancillary properties of carvedilol are critical to its benefit in CHF patients. This question is currently being addressed in the Carvedilol and Metoprolol European Trial (COMET), comparing metoprolol with carvedilol. The beneficial effects of beta-blockers on mortality in patients with mild to moderate CHF have also had major implications in ongoing studies of other agents in this condition. Open-label prescribing of beta-blockers is increasing in these studies and this is having an impact on event rates and thus required duration of administration of study drug. Furthermore, it would now appear unethical to deprive suitable NYHA Class II-III CHF patients of beta-blockers as part of the design of such studies. In conclusion, beta-blockers have now become the most extensively studied class of agents in the treatment of CHF, with a database of over 6000 patients in placebo-controlled studies, and ongoing clinical and mechanistic studies. Despite this, further questions remain regarding the use of these agents in CHF, including their role in the extreme elderly, in patients with diabetes mellitus and in patients with renal impairment.
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PMID:Beta-blockers in heart failure. The 'new wave' of clinical trials. 1047 16

Bisoprolol is a highly selective beta(1)-adrenoceptor antagonist. Administration of bisoprolol to patients with chronic heart failure is associated with increases in left ventricular function and reductions in heart rate; increases in heart rate variability are also seen. Two major randomised, double-blind, placebo-controlled, multicentre trials have examined the clinical efficacy of bisoprolol in combination with ACE inhibitors and diuretics in patients with stable chronic heart failure (New York Heart Association class III or IV): the Cardiac Insufficiency Bisoprolol Study (CIBIS; n = 641) and CIBIS II (n = 2 647). All-cause mortality (primary endpoint) was significantly lower in bisoprolol than in placebo recipients in CIBIS II (11.8 vs 17.3%) and was reduced by bisoprolol regardless of dosage. All-cause mortality was also lower in CIBIS (16.6 vs 20.9%) although the difference did not achieve statistical significance. In a meta-analysis of CIBIS and CIBIS II (n = 3 288), a relative reduction of 29% in the incidence of all-cause mortality was seen in bisoprolol versus placebo recipients; this analysis also demonstrated that bisoprolol reduces mortality in patients with chronic heart failure regardless of aetiology or severity. In CIBIS II, there were significantly fewer cardiovascular deaths, admissions to hospital for any reason, or cardiovascular deaths or cardiovascular hospitalisations (combined endpoint) in bisoprolol, compared with placebo, recipients (secondary endpoints). Compared with standard treatment alone, the addition of bisoprolol was a cost-effective option in chronic heart failure in UK, French, German and Swedish pharmacoeconomic studies. Bisoprolol is generally well tolerated in patients with chronic heart failure. In CIBIS II, adverse events occurring more commonly in bisoprolol than placebo recipients, regardless of causal relationship with the study medication, included dizziness, bradycardia, hypotension and fatigue. Bisoprolol recipients were less likely than placebo recipients to experience worsening of heart failure, dyspnoea or tachycardia. In both CIBIS and CIBIS II there was no significant difference between bisoprolol and placebo recipients in the incidence of permanent treatment withdrawal. In conclusion, adding the highly selective beta(1)-blocker bisoprolol to a treatment regimen comprising an ACE inhibitor and a diuretic significantly improves survival in patients with stable chronic heart failure and reduces the need for hospitalisation. The use of bisoprolol in this disorder is generally well tolerated and is cost effective. Thus, bisoprolol should be considered a standard treatment option when selecting a beta-blocker for use in combination with ACE inhibitors and diuretics in patients with stable, moderate to severe chronic heart failure.
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PMID:Bisoprolol: a review of its use in chronic heart failure. 1246 13

Chronic heart failure affects between 1-5% of the population and rise steeply with age. Most patients with chronic heart failure should be routinely managed with a combination of 4 types of drugs: a diuretic, an angiotensin converting enzyme inhibitors (ACE-I), beta-blocker and usually digitalis. Diuretics are essential for symptomatic treatment when fluid overload is present, and should always be administrated in combination with ACE-I if possible. ACE-I improves survival and symptoms and reduces hospitalization in patients with moderate to severe ventricular systolic dysfunction, and in the absence of fluid retention should be given first. Angiotensin II receptor antagonist could be considered in patients who not tolerate ACE-I. beta-blocking agents are recommended for treatment of patients with stable, mild, moderate and severe heart failure unless there is a contraindication. Bisoprolol, metoprolol and carvedilol have been associated with reduction in total mortality, cardiovascular mortality and sudden death. Cardiac glycosides are indicated in atrial fibrillation and any degree of symptomatic heart failure in order slow ventricular rate. Indications for antiarrhythmic drug therapy include atrial fibrillation, non-sustained or sustained ventricular tachycardia. Oral anticoagulation reduces the risk of stroke in patients with atrial fibrillation, and there is a lack of evidence to support the use of antithrombotic therapy in patients in sinus rhythm.
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PMID:[Pharmacotherapy of chronic heart failure in clinical practice]. 1551 21

The life-time risk of developing HF is about 20% (40% if hypertension present). With increasing longevity in the developed world the burden of HF (hospitalisation) is set to increase over the next 10-20 years. CAD and hypertension are the two main causes of HF; CAD (and obesity) in the case of systolic HF and hypertension in the case of diastolic HF (mainly in the elderly). BB have become the corner-stone (alongside ACE-inhibitors) in the treatment of systolic HF. Bisoprolol, metoprolol and carvedilol (on an ACE-inhibitor background) have reduced all-cause death by 34-5%. The presence of intrinsic sympathomemetic activity (xamoterol, bucindolol, nebivolol) diminishes efficacy in the treatment of systolic HF. First-line bisoprolol has proved "non-inferior" to first-line enalapril in reducing all-cause death and is probably superior in reducing sudden death. The main mode of action of BB in treating systolic HF is inhibition of chronic beta-1 stimulation-induced myocardial apoptosis/necrosis/inflammation. The combination of pure beta-1 blockade (low-dose bisoprolol) and pure beta-2 blockade (clenbuterol) may prove invaluable in the treatment of end-stage systolic HF (thus avoiding cardiac transplantation). The appropriate treatment of diastolic HF has yet to be determined. Beta-blockade is effective in the prevention of HF i) in the post-MI period and ii) as first-line agents in the treatment of young/middle-aged hypertension and as second-line agents (to first-line diuretics) in the treatment of elderly systolic hypertension. BB are highly effective in reversing LVH in young/middle-aged hypertensives (LVH pre-disposes to HF in young/middle-aged hypertension) and are (bisoprolol) at least as good as ACE-inhibitors. Choice of BB is important as benefit is not a class-effect. ISA (xamoterol, bucindolol, nebivolol) markedly diminishes efficacy. The choice is between bisoprolol, metoprolol succinate and carvedilol for optimal efficacy. Adverse reactions are associated, mainly, with beta-2 blockade and alpha-blockade. Thus non-selective (e.g. propranolol) or modestly beta-1 selective (e.g. metoprolol, atenolol) are associated with metabolic disturbance, bronchospasm, epinephrine/hypertensive interaction (with cigarette-smoking or insulin-induced hypoglycaemia), while the possession of alpha-blocking activity (e.g. carvedilol) is associated with dizziness and postural hypotension. The possession of beta-2 blockade, particularly if combined with alpha-blockade, is associated with an increased occurrence of sexual dysfunction. Lipophilic BB like propranolol and metoprolol appear in high concentrations in human brain tissue and are associated with side-effects such as insomnia, dreams and nightmares.
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PMID:Beta-blockers and heart failure. 2118 Feb 98