2000 Feb 19;320(7233):495-8 [Texto
ABC of heart failure. Management: digoxin and other inotropes, beta
and antiarrhythmic and antithrombotic treatment.
Gibbs CR, Davies MK, Lip GY
University Department of Medicine and the Department of Cardiology, City
Am J Cardiol 1999 Nov 4;84(9A):76R-82R
Mortality reduction by antiadrenergic modulation of arrhythmogenic
significance of combining beta blockers and amiodarone.
Ogunyankin KO, Singh BN
Division of Cardiology, Bassett Healthcare, Cooperstown, New York 13326,
Over the last 3 decades, there have been numerous experimental and
studies that utilized beta blockers for acute as well as chronic
syndromes, especially in the setting of myocardial infarction in which the
has been on mortality reduction. The results of these studies demonstrated
benefits of these agents at all stages of coronary artery disease.
these data have always indicated that beta blockade per se is an
as well as an antifibrillatory mechanism, the recognition of this
been slow in finding universal appreciation. More recent studies have
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
(VT) and ventricular fibrillation (VF), thereby reducing sudden arrhythmic
and prolonging survival. It is of interest that 2 of the leading
drugs, amiodarone and sotalol, also have antiadrenergic properties. This
reviews the expanding role of beta-blocking drugs in the control and
of life-threatening ventricular tachyarrhythmias with a particular focus
evidence for synergistic benefits when they are combined with other
interventions, especially amiodarone.
Clin Cardiol 1999 Oct;22 Suppl 5:V21-9
Experience with beta blockers in heart failure mortality trials.
University of Texas Southwestern Medical Center, Dallas 75216, USA.
Recent investigations have indicated that chronic heart failure can be
with agents that inhibit the reninangiotensin-aldosterone or sympathetic
system, such as angiontensin-converting enzyme (ACE) inhibitors and beta
blockers. A meta-analysis of clinical trials of ACE inhibition in chronic
failure reported reductions in mortality ranging from 13 to 33%, but as
inhibitors do not block chronic noradrenergic stimulation of the heart,
mortality remains unacceptably high. Beta blockers have been shown to
left ventricular ejection fraction, reduce end-systolic and end-diastolic
cardiac dimensions, improve quality of life, and reduce mortality.
mortality in the US Carvedilol trial was reduced 65%, and in MERIT-HF
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
differences in disease severity, race, and age should be answered as large
ongoing and planned clinical trials of beta blockers are completed.
Clin Cardiol 1999 Oct;22 Suppl 5:V16-20
The cellular and physiologic effects of beta blockers in heart failure.
Department of Medicine, Henry Ford Heart and Vascular Institute, Henry
Health System, Detroit, Michigan, USA.
Enhanced and sustained cardiac adrenergic drive occurs in heart failure
contributes, in part, to the progression of left ventricular (LV)
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
reserve and exercise tolerance. This sympathoadrenergic maladaptation can
lead to cellular abnormalities in the failing heart, manifested by defects
calcium handling of the sarcoplasmic reticulum, by defects in myocardial
energetics, and by ongoing loss of cardiomyocytes through necrosis or
Chronic treatment with beta blockers in patients with HF and in animals
experimentally induced HF has been shown to reverse, prevent, or, at the
arrest many, if not all, of these adverse processes. Beta blockers improve
function of the failing LV, prevent or reverse progressive LV dilation,
sphericity, and hypertrophy, and consequently have positive impact on
remodeling. Beta blockers also reduce heart rate and LV wall stress,
reduced myocardial oxygen consumption, a clear benefit to the failing
Beta blockers can also improve the intrinsic contractile function of
cardiomyocytes and have also been shown to improve myocardial energetics
possibly through desirable changes in substrate utilization. Recent
our laboratories have also shown that beta blockers can attenuate
apoptosis in HF. These benefits provide strong reinforcement to the
findings that beta blockers are highly beneficial for the management of
with chronic HF and, when properly used, afford unequivocal reductions in
mortality and morbidity in this patient population. At present, there is
agreement that increased cardiac sympathetic drive occurs in HF and may
potentially be an important contributor to the progression of LV
chamber remodeling that is characteristic of this disease state.
studies in animal models of HF as well as clinical studies in patients
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
sphericity. Results of recent multicenter clinical trials support these
and have made it abundantly clear that long-term therapy with beta
inhibits clinical progression and has a major impact on mortality and
in patients with HF that is at least as favorable, if not better, than
observed with angiotensin-converting enzyme (ACE) inhibitors. Beta
improve mortality and morbidity in HF and also improve LV ejection
(EF), a beneficial feature that, until recently, has only been attributed
positive inotropic agents.
Clin Cardiol 1999 Oct;22 Suppl 5:V11-5
Prevention of sudden cardiac death with beta blockers.
Institute of Heart and Lung Diseases, Sahlgrenska University Hospital,
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
to 50%. These reductions are substantially greater than trials of other
classes including angiotensin-converting enzyme inhibitors. However, not
beta blockers confer equal benefit to patients at risk of sudden cardiac
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
pronounced clinical effects. Based on the results of numerous clinical and
mechanistic studies, it is suggested that beta blockers should be given to
patients at risk for sudden cardiac death, including those patients with
previous myocardial infarction, hypertension, or congestive heart failure.
Clin Exp Hypertens 1999 Jul-Aug;21(5-6):815-21
Drug treatment--antihypertensive drugs--the present role of beta blockers
Department of Medicine and Therapeutics, University of Glasgow, Scotland,
There are several lines of evidence implicating increased sympathetic
not only in the maintenance of raised blood pressure but in the
of hypertensive complications including atherosclerosis. Beta blockers are
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
reinfarction in patients after myocardial infarction and to improve
patients with congestive heart failure. Side effects of beta blockers are
predictable and result from excess pharmacological activity. They can
controlled by dose adjustments. Alpha blockers reduce peripheral
They are as effective as other classes at lowering blood pressure although
date there is little or no long term outcome data with this class.
sympathetic activity with beta and/or alpha blockers should remain amongst
first choices for monotherapy (or add-on therapy) in essential
Am Fam Physician 1998 Nov 1;58(7):1627-34, 1641-2 [Texto
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
despite reduced mortality rates resulting from the addition of angiotensin
converting enzyme inhibitors to traditional treatment regimens. Because
the myocardial damage that occurs in patients with CHF may be related to
sympathetic activation, interest in the use of beta blockers has grown.
studies have shown the benefits of beta blocker therapy in many patients
heart failure. Carvedilol, the first beta blocker labeled in the United
specifically for the treatment of heart failure, has been shown to improve
ventricular ejection fraction and may reduce mortality.
Am J Med 1998 Feb;104(2):163-9
Restoring function in failing hearts: the effects of beta blockers.
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,
hemodynamic abnormalities, and enhanced functional status, but they failed
confer a survival benefit. Indeed, the use of inotropic agents often
excess mortality--a paradox explained in part by the pharmacological
of these agents, which increase production of cAMP, the intracellular
for the beta-adrenergic system. The short-term pharmacological benefits of
drugs may be offset by deleterious long-term biological effects on the
muscle itself. The use of beta-blockers in heart failure is
given that their initial pharmacological effect is to reduce heart rate
contractility in a faltering heart, thus producing an effect diametrically
opposed to that of inotropic agents. However, it is becoming more clear
beta-blocker therapy in patients with heart failure not only improves left
ventricular function, but may actually reverse pathological remodeling in
heart. Accumulating clinical evidence indicates that these beneficial
are the result of secondary biological changes in the myocardium rather
response to the pharmacological effects of the drugs themselves. Mounting
evidence suggest that these agents may prolong survival in patients with
failure, and ongoing clinical trials may soon confirm these preliminary
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.
Henry Ford Heart and Vascular Institute, Henry Ford Hospital, Detroit,
With greater understanding of the impact of neuroendocrine stimulation on
adverse outcomes of heart failure, especially lethal arrhythmias and
cardiac death, focus has returned to the potential benefits of
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
and improved survival. Even in the absence of angiotensin-converting
(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
Dilated Cardiomyopathy (MDC) trial and the Cardiac Insufficiency
Study (CIBIS) found beta blockade to be associated with decreased
rates in patients with nonischemic heart failure. Of the 3 large
randomized mortality trials now under way, the Metoprolol CR/XL Randomized
Trial in Heart Failure (MERIT-HF) is specifically designed to investigate
effects of beta blockade on total mortality when used as an adjunct to ACE
inhibition in patients with ischemic or nonischemic heart failure.
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
failure; (3) any specific beta blocker may be better tolerated initially
cause fewer adverse effects; and (4) all beta blockers result in improved
exercise tolerance and quality of life.
Am J Cardiol 1997 Nov 13;80(9B):45J-49J
Efficacy of beta blockers in idiopathic dilated cardiomyopathy and
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
heart failure has, however, brought beta blockade into focus. There is
experimental evidence for the value of blocking sympathetic activation in
and increased sympathetic activation may be an etiologic factor for
of CHF. Clinical studies have shown that long-term beta blockade improves
systolic and diastolic function. The effects on exercise tolerance and
of life seem to differ between beta1-selective and nonselective beta
favor of the beta1-selective blockers. To date, results of all trials
consistent pattern of decreased cardiovascular morbidity. In one trial of metoprolol, fewer heart transplantations were required; such a reduction
have a great impact on healthcare costs associated with heart failure.
long-term survival found by one study must be confirmed in additional
such survival trials (with metoprolol, bisoprolol, and bucindolol) are now
Am J Cardiol 1997 Nov 13;80(9B):15J-19J
Clinical relevance of pharmacokinetic differences between beta blockers.
Department of Medicine, University of Brimingham, Edgbaston, England,
Fundamental differences in the pharmacodynamic and pharmacokinetic
beta-adrenergic blocking agents must be considered in optimizing their
and determining the appropriate selection of these drugs in different
Beta blockers are contraindicated in patients with asthma and should be
cautiously in heart failure. Clinically important distinctions are related
whether a beta blocker is beta1-selective or nonselective. Most adverse
of beta-blocker use are related to interference with beta2-mediated
including bronchodilation, vasodilation, and mobilization of free fatty
To achieve the potential benefits of beta1 blockade (decreased heart rate,
pressure, cardiac workload, and excitability), a low plasma concentration
beta1-selective drug is required. Adverse effects of beta blockers can be
further decreased by selecting a sustained-release beta1-selective drug.
blockers are further differentiated on the basis of lipophilicity or
hydrophilicity. Lipophilic beta blockers cross the blood-brain barrier,
hydrophilic agents do not enter the central nervous system. Some
agents (metroprolol, timolol, and propanolol) have been shown to decrease
mortality in coronary heart disease, particularly sudden cardiac death.
Clin Cardiol 1994 Aug;17(8):415-21
Concomitant use of nitrates, calcium channel blockers, and beta blockers
optimal antianginal therapy.
Department of Medicine, State University of New York Health Sciences
Stony Brook 11794-8171.
Despite the introduction of new mechanical techniques for
pharmacologic therapy continues to be the mainstay of antianginal therapy.
conventional antianginal medications, which include nitrates, beta
calcium channel blockers, act to correct the imbalance between myocardial
and demand by increasing coronary blood flow, reducing myocardial oxygen
requirements, or both. All three are appropriate for the management of
caused by a fixed coronary obstruction, but nitrates and calcium channel
blockers, which not only reduce demand but also increase supply, are
in cases of angina believed to involve a significant increase in vasomotor
Because of the different yet complementary mechanisms of action of the
classes of anti-ischemic drugs, use of these agents in combination is a
approach to the treatment of angina unresponsive to monotherapy. Such
combinations have been shown to enhance the therapeutic response achieved
single-agent therapy. In addition, the pharmacologic action of one of the
components of the combination regimen may serve to offset side effects
associated with the other.
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.