LA CONSULTA SEMANAL

ENERO 2001

CONSULTA

BMJ 2000 Feb 19;320(7233):495-8 [Texto completo]
ABC of heart failure. Management: digoxin and other inotropes, beta blockers, and antiarrhythmic and antithrombotic treatment.
Gibbs CR, Davies MK, Lip GY
University Department of Medicine and the Department of Cardiology, City Hospital, Birmingham.
Publication Types:
  Review
  Review, tutorial


Am J Cardiol 1999 Nov 4;84(9A):76R-82R
Mortality reduction by antiadrenergic modulation of arrhythmogenic substrate: significance of combining beta blockers and amiodarone.
Ogunyankin KO, Singh BN
Division of Cardiology, Bassett Healthcare, Cooperstown, New York 13326, USA.
Over the last 3 decades, there have been numerous experimental and clinical studies that utilized beta blockers for acute as well as chronic myocardial syndromes, especially in the setting of myocardial infarction in which the focus has been on mortality reduction. The results of these studies demonstrated the benefits of these agents at all stages of coronary artery disease. Although these data have always indicated that beta blockade per se is an antiarrhythmic as well as an antifibrillatory mechanism, the recognition of this phenomenon has been slow in finding universal appreciation. More recent studies have evaluated the additive role of beta blockers to newer therapies. A number of investigations have now established that this class of drugs does exert antifibrillatory action in preventing the occurrence of ventricular tachycardia (VT) and ventricular fibrillation (VF), thereby reducing sudden arrhythmic death and prolonging survival. It is of interest that 2 of the leading antiarrhythmic drugs, amiodarone and sotalol, also have antiadrenergic properties. This article reviews the expanding role of beta-blocking drugs in the control and prevention of life-threatening ventricular tachyarrhythmias with a particular focus on the evidence for synergistic benefits when they are combined with other interventions, especially amiodarone.
Publication Types:
  Review
  Review, tutorial


Clin Cardiol 1999 Oct;22 Suppl 5:V21-9
Experience with beta blockers in heart failure mortality trials.
Eichhorn EJ
University of Texas Southwestern Medical Center, Dallas 75216, USA.
Recent investigations have indicated that chronic heart failure can be reversed with agents that inhibit the reninangiotensin-aldosterone or sympathetic nervous system, such as angiontensin-converting enzyme (ACE) inhibitors and beta blockers. A meta-analysis of clinical trials of ACE inhibition in chronic heart failure reported reductions in mortality ranging from 13 to 33%, but as ACE inhibitors do not block chronic noradrenergic stimulation of the heart, mortality remains unacceptably high. Beta blockers have been shown to increase left ventricular ejection fraction, reduce end-systolic and end-diastolic cardiac dimensions, improve quality of life, and reduce mortality. All-cause mortality in the US Carvedilol trial was reduced 65%, and in MERIT-HF there was a 49% reduction in mortality from heart failure among patients receiving metoprolol CR/XL. MERIT-HF was ended early because of evidence of survival benefit. Although certain effects of beta blockers may be considered class effects, it is not yet clear whether there are differences between beta 1-selective antagonists and nonselective agents. The benefits conferred across differences in disease severity, race, and age should be answered as large ongoing and planned clinical trials of beta blockers are completed.
Publication Types:
  Review
  Review, tutorial


Clin Cardiol 1999 Oct;22 Suppl 5:V16-20
The cellular and physiologic effects of beta blockers in heart failure.
Sabbah HN
Department of Medicine, Henry Ford Heart and Vascular Institute, Henry Ford Health System, Detroit, Michigan, USA.
Enhanced and sustained cardiac adrenergic drive occurs in heart failure (HF) and contributes, in part, to the progression of left ventricular (LV) dysfunction and remodeling that are characteristic of this disease state. Enhanced sympathetic drive in HF can lead to downregulation and desensitization of cardiac beta-adrenergic receptors with a consequent impairment of myocardial reserve and exercise tolerance. This sympathoadrenergic maladaptation can also lead to cellular abnormalities in the failing heart, manifested by defects in calcium handling of the sarcoplasmic reticulum, by defects in myocardial energetics, and by ongoing loss of cardiomyocytes through necrosis or apoptosis. Chronic treatment with beta blockers in patients with HF and in animals with experimentally induced HF has been shown to reverse, prevent, or, at the least, arrest many, if not all, of these adverse processes. Beta blockers improve function of the failing LV, prevent or reverse progressive LV dilation, chamber sphericity, and hypertrophy, and consequently have positive impact on cardiac remodeling. Beta blockers also reduce heart rate and LV wall stress, leading to reduced myocardial oxygen consumption, a clear benefit to the failing heart. Beta blockers can also improve the intrinsic contractile function of cardiomyocytes and have also been shown to improve myocardial energetics in HF, possibly through desirable changes in substrate utilization. Recent studies from our laboratories have also shown that beta blockers can attenuate cardiomyocyte apoptosis in HF. These benefits provide strong reinforcement to the clinical findings that beta blockers are highly beneficial for the management of patients with chronic HF and, when properly used, afford unequivocal reductions in mortality and morbidity in this patient population. At present, there is general agreement that increased cardiac sympathetic drive occurs in HF and may potentially be an important contributor to the progression of LV dysfunction and chamber remodeling that is characteristic of this disease state. Experimental studies in animal models of HF as well as clinical studies in patients with HF have suggested that chronic therapy with beta blockade is effective in preventing the progression of LV dysfunction and remodeling, the latter evidenced by reversal and/or prevention of progressive LV dilation and chamber sphericity. Results of recent multicenter clinical trials support these findings and have made it abundantly clear that long-term therapy with beta blockade inhibits clinical progression and has a major impact on mortality and morbidity in patients with HF that is at least as favorable, if not better, than that observed with angiotensin-converting enzyme (ACE) inhibitors. Beta blockers improve mortality and morbidity in HF and also improve LV ejection fraction (EF), a beneficial feature that, until recently, has only been attributed to positive inotropic agents.
Publication Types:
  Review
  Review, tutorial


Clin Cardiol 1999 Oct;22 Suppl 5:V11-5
Prevention of sudden cardiac death with beta blockers.
Hjalmarson A
Institute of Heart and Lung Diseases, Sahlgrenska University Hospital, Goteborg, Sweden.
Beta blockers have been shown to reduce the risk of sudden cardiac death in more  than 50 randomized trials involving more than 55,000 patients. Relative reductions (vs. placebo) in cardiac death in some of these trials ranged from 30 to 50%. These reductions are substantially greater than trials of other drug classes including angiotensin-converting enzyme inhibitors. However, not all beta blockers confer equal benefit to patients at risk of sudden cardiac death. Results from various trials suggest that lipophilic beta blockers--such as timolol, metoprolol, propranolol, bisoprolol, and carvedilol--may be more beneficial than hydrophilic beta blockers. Results of animal studies have indicated that sudden cardiac death is mediated, at least in part, by the central nervous system, which may account for why lipophilic agents have more pronounced clinical effects. Based on the results of numerous clinical and mechanistic studies, it is suggested that beta blockers should be given to all patients at risk for sudden cardiac death, including those patients with previous myocardial infarction, hypertension, or congestive heart failure.
Publication Types:
  Review
  Review, tutorial


Clin Exp Hypertens 1999 Jul-Aug;21(5-6):815-21
Drug treatment--antihypertensive drugs--the present role of beta blockers and alpha blockers.
Reid JL
Department of Medicine and Therapeutics, University of Glasgow, Scotland, UK.
There are several lines of evidence implicating increased sympathetic activity not only in the maintenance of raised blood pressure but in the pathophysiology of hypertensive complications including atherosclerosis. Beta blockers are one of the best documented classes of drugs in terms of long term safety and improvement in outcome in hypertension. They are also well established to reduce reinfarction in patients after myocardial infarction and to improve survival in patients with congestive heart failure. Side effects of beta blockers are predictable and result from excess pharmacological activity. They can often be controlled by dose adjustments. Alpha blockers reduce peripheral resistance. They are as effective as other classes at lowering blood pressure although to date there is little or no long term outcome data with this class. Reduction of sympathetic activity with beta and/or alpha blockers should remain amongst the first choices for monotherapy (or add-on therapy) in essential hypertension.
Publication Types:
  Review
  Review, tutorial


Am Fam Physician 1998 Nov 1;58(7):1627-34, 1641-2 [Texto completo]
Carvedilol: the new role of beta blockers in congestive heart failure.
Vanderhoff BT, Ruppel HM, Amsterdam PB
Grant Medical Center, Columbus, Ohio, USA.
The prognosis remains poor for patients with congestive heart failure (CHF), despite reduced mortality rates resulting from the addition of angiotensin converting enzyme inhibitors to traditional treatment regimens. Because much of the myocardial damage that occurs in patients with CHF may be related to sympathetic activation, interest in the use of beta blockers has grown. Recent studies have shown the benefits of beta blocker therapy in many patients with heart failure. Carvedilol, the first beta blocker labeled in the United States specifically for the treatment of heart failure, has been shown to improve left ventricular ejection fraction and may reduce mortality.
Publication Types:
  Review
  Review, tutorial


Am J Med 1998 Feb;104(2):163-9
Restoring function in failing hearts: the effects of beta blockers.
Eichhorn EJ
Department of Internal Medicine (Division of Cardiology), Dallas Veterans Administration Hospital, Texas 75216, USA.
Until recently, clinical management of congestive heart failure was purely palliative. The drugs used in patients with failing hearts--digoxin, vasodilators, and positive inotropic agents--improved contractility, reversed hemodynamic abnormalities, and enhanced functional status, but they failed to confer a survival benefit. Indeed, the use of inotropic agents often resulted in excess mortality--a paradox explained in part by the pharmacological properties of these agents, which increase production of cAMP, the intracellular messenger for the beta-adrenergic system. The short-term pharmacological benefits of these drugs may be offset by deleterious long-term biological effects on the heart muscle itself. The use of beta-blockers in heart failure is counterintuitive, given that their initial pharmacological effect is to reduce heart rate and contractility in a faltering heart, thus producing an effect diametrically opposed to that of inotropic agents. However, it is becoming more clear that beta-blocker therapy in patients with heart failure not only improves left ventricular function, but may actually reverse pathological remodeling in the heart. Accumulating clinical evidence indicates that these beneficial changes are the result of secondary biological changes in the myocardium rather than a response to the pharmacological effects of the drugs themselves. Mounting evidence suggest that these agents may prolong survival in patients with heart failure, and ongoing clinical trials may soon confirm these preliminary findings.
Publication Types:
  Review
  Review, tutorial


Am J Cardiol 1997 Nov 13;80(9B):50J-53J
Clinical studies on beta blockers and heart failure preceding the MERIT-HF Trial. Metoprolol CR/XL Randomized Intervention Trial in Heart Failure.
Goldstein S
Henry Ford Heart and Vascular Institute, Henry Ford Hospital, Detroit, Michigan 48202-2689, USA.
With greater understanding of the impact of neuroendocrine stimulation on the adverse outcomes of heart failure, especially lethal arrhythmias and sudden cardiac death, focus has returned to the potential benefits of beta-adrenergic blockade. In patients with myocardial infarction and left ventricular (LV) dysfunction, particularly those prone to life-threatening arrhythmias, beta-blocker therapy has been associated with a lower incidence of arrhythmias and improved survival. Even in the absence of angiotensin-converting enzyme (ACE) inhibition, beta blockade has improved cardiac function and LV contractility in nonischemic heart failure, leading to a decrease in LV end-diastolic pressure and improved clinical status. Both the Metoprolol in Dilated Cardiomyopathy (MDC) trial and the Cardiac Insufficiency Bisoprolol Study (CIBIS) found beta blockade to be associated with decreased mortality rates in patients with nonischemic heart failure. Of the 3 large randomized mortality trials now under way, the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF) is specifically designed to investigate the effects of beta blockade on total mortality when used as an adjunct to ACE inhibition in patients with ischemic or nonischemic heart failure. Unresolved issues to be addressed include whether: (1) beta-blocker therapy in heart failure can improve survival and/or reduce the incidence of sudden cardiac death; (2) beta blockade is equally effective in ischemic and nonischemic heart failure; (3) any specific beta blocker may be better tolerated initially and cause fewer adverse effects; and (4) all beta blockers result in improved exercise tolerance and quality of life.
Publication Types:
  Review
  Review, tutorial


Am J Cardiol 1997 Nov 13;80(9B):45J-49J
Efficacy of beta blockers in idiopathic dilated cardiomyopathy and ischemic cardiomyopathy.
Waagstein F
Division of Cardiology, Sahlgrenska University Hospital, Goteborg, Sweden.
Despite the well-documented benefits of beta blockade in a variety of cardiovascular conditions, the value of beta blockade in congestive heart failure (CHF) is still in question. The concept of neurohormonal blockade in heart failure has, however, brought beta blockade into focus. There is experimental evidence for the value of blocking sympathetic activation in CHF, and increased sympathetic activation may be an etiologic factor for development of CHF. Clinical studies have shown that long-term beta blockade improves both systolic and diastolic function. The effects on exercise tolerance and quality of life seem to differ between beta1-selective and nonselective beta blockers in favor of the beta1-selective blockers. To date, results of all trials reveal a consistent pattern of decreased cardiovascular morbidity. In one trial of metoprolol, fewer heart transplantations were required; such a reduction may have a great impact on healthcare costs associated with heart failure. Improved long-term survival found by one study must be confirmed in additional trials: 3 such survival trials (with metoprolol, bisoprolol, and bucindolol) are now in progress.
Publication Types:
  Review
  Review, tutorial


Am J Cardiol 1997 Nov 13;80(9B):15J-19J
Clinical relevance of pharmacokinetic differences between beta blockers.
Kendall MJ
Department of Medicine, University of Brimingham, Edgbaston, England, United Kingdom.
Fundamental differences in the pharmacodynamic and pharmacokinetic profiles of beta-adrenergic blocking agents must be considered in optimizing their efficacy and determining the appropriate selection of these drugs in different patients. Beta blockers are contraindicated in patients with asthma and should be used cautiously in heart failure. Clinically important distinctions are related to whether a beta blocker is beta1-selective or nonselective. Most adverse effects of beta-blocker use are related to interference with beta2-mediated functions including bronchodilation, vasodilation, and mobilization of free fatty acids. To achieve the potential benefits of beta1 blockade (decreased heart rate, blood pressure, cardiac workload, and excitability), a low plasma concentration of a beta1-selective drug is required. Adverse effects of beta blockers can be further decreased by selecting a sustained-release beta1-selective drug. Beta blockers are further differentiated on the basis of lipophilicity or hydrophilicity. Lipophilic beta blockers cross the blood-brain barrier, whereas hydrophilic agents do not enter the central nervous system. Some lipophilic agents (metroprolol, timolol, and propanolol) have been shown to decrease mortality in coronary heart disease, particularly sudden cardiac death.
Publication Types:
  Review
  Review, tutorial


Clin Cardiol 1994 Aug;17(8):415-21
Concomitant use of nitrates, calcium channel blockers, and beta blockers for optimal antianginal therapy.
Cohn PF
Department of Medicine, State University of New York Health Sciences Center, Stony Brook 11794-8171.
Despite the introduction of new mechanical techniques for revascularization, pharmacologic therapy continues to be the mainstay of antianginal therapy. The conventional antianginal medications, which include nitrates, beta blockers, and calcium channel blockers, act to correct the imbalance between myocardial supply and demand by increasing coronary blood flow, reducing myocardial oxygen requirements, or both. All three are appropriate for the management of angina caused by a fixed coronary obstruction, but nitrates and calcium channel blockers, which not only reduce demand but also increase supply, are preferred in cases of angina believed to involve a significant increase in vasomotor tone. Because of the different yet complementary mechanisms of action of the three classes of anti-ischemic drugs, use of these agents in combination is a rational approach to the treatment of angina unresponsive to monotherapy. Such combinations have been shown to enhance the therapeutic response achieved with single-agent therapy. In addition, the pharmacologic action of one of the components of the combination regimen may serve to offset side effects typically associated with the other.
Publication Types:
  Review
  Review, tutorial


Med Clin (Barc) 1994 Feb 19;102(6):231-5
[Beta blockers, fibrinogen, and atherosclerosis].
[Article in Spanish]
Serrano Aguilar PG
Instituto Nacional de la Salud, Tejina, La Laguna, Santa Cruz de Tenerife.
Publication Types:
  Review
  Review, tutorial