Editorials: Beta Blockers and Congestive Heart Failure - American Family Physician
Heart failure, the only cardiovascular disease with an increasing incidence, is associated with significant mortality and poses a considerable economic burden. Can beta blockers cause heart failure, beta blockers have been considered to be contraindicated in patients with heart failure.
Recently, slots to win real money, several large randomized, controlled mortality trials have been stopped early because of significant improvement in mortality rates in patients with heart failure who were given beta blockers in addition to angiotensin-converting enzyme inhibitors, diuretics and, sometimes, digoxin.
Beta blockers can beta blockers cause heart failure now be considered standard therapy in patients with New York Heart Association class II or class III heart failure who are hemodynamically stable, who do not have dyspnea at rest and who have no other contraindications to the use of these agents. Congestive heart failure is a significant public health problem that affects an estimated 4.
The can beta blockers cause heart failure incidence of congestive heart www megacasino is in contrast to the decreasing incidence of other cardiovascular disorders.
InMedicare spent 5. Despite the magnitude of the problem, treatment of congestive heart failure is often inadequate. Most patients with heart failure are cared for by primary care physicians. Recently, three large, randomized, controlled trials demonstrated a substantial mortality benefit for beta-blocker therapy in patients with heart failure. As the number of effective interventions increases, it has become increasingly important for primary care physicians to stay can beta blockers cause heart failure of developments in heart failure treatment.
As the understanding of heart failure has advanced, it has become important to separate systolic dysfunction from diastolic dysfunction because the etiology, treatment and prognosis of these disorders is quite different.
The discussion in this article is limited to heart failure resulting from left ventricular systolic dysfunction, defined as an ejection fraction of less check this out 40 percent. Left ventricular systolic dysfunction is a mechanical defect i. The impact of this dysfunction is manifested in hemodynamic and physiologic abnormalities, including decreased cardiac output, elevated pulmonary capillary wedge pressure and decreased exercise tolerance.
Historically, interventions to treat patients with heart failure have been directed at improving these hemodynamic end points. However, clinical trials found a lack of correlation between hemodynamic improvement and clinical improvement, and new strategies were sought.
Recent studies have revealed a correlation between prognosis in heart failure and plasma levels of such neurohormones as endothelin, 14 norepinephrine 15 and renin, 16 among others. Neurohormones have also been shown to stimulate necrosis, fibrosis and apoptosis in the heart. As a result, a neurohormonal hypothesis has evolved to describe how activation of these neurohormonal systems may cause progression of heart failure. Elevated levels of norepinephrine may affect individual myocytes, heart rate, peripheral resistance and, perhaps, other neurohormonal systems.
Blocking the impact of norepinephrine by blocking beta receptors would, in theory, block the adverse affects of norepinephrine. The clinical trials described in this article provide evidence that currently available beta-blocking agents intended to block this neurohormonal process have a significant positive clinical impact in patients with heart failure.
Bisoprolol Zebeta is a selective beta 1 antagonist without significant intrinsic sympathetic activity or vasodilating properties Table 1. Two randomized, controlled mortality trials of bisoprolol have been completed in patients with heart here Table 2. Placebo mortality was lower than expected and decreased the statistical power of the study.
No significant difference was found in the death rate from progressive pump failure. Information from A randomized trial of beta-blockade in heart failure. The Cardiac Can beta blockers cause heart failure Bisoprolol Study CIBIS. CIBIS Investigators and Committees.
The Cardiac Insufficiency Bisoprolol Study CIBIS 18 was the first true mortality trial of beta antagonists. The absolute mortality rate at the end of the approximately month surveillance period was However, bisoprolol was titrated up to the target dosage can beta blockers cause heart failure 5 mg per day in only one half of treated patients; this may have affected the outcome of the study.
Nonetheless, CIBIS demonstrated the safety of betway bingo, along with a significant improvement in New York Heart Association NYHA class Table 3 and a decrease in hospitalizations in the patients who received bisoprolol.
CIBIS-II was similar to CIBIS but had go here statistical power to detect a mortality benefit for bisoprolol therapy. CIBIS-II also had approximately four times as many patients as CIBIS, included more patients with NYHA class IV symptoms and used a higher dosage of bisoprolol.
The benefits applied irrespective of the etiology of the heart failure. There were 42 percent fewer sudden deaths in the bisoprolol-treated patients.
This improvement was statistically significant and accounted for almost all of the mortality benefit. The decreased death rates from other causes were not significant. Like bisoprolol, metoprolol tartrate Lopressor and metoprolol succinate Toprol XL are beta 1 -selective blockers without significant intrinsic sympathetic activity or vasodilating properties.
Reports have been published from two mortality trials on the effectiveness of metoprolol in patients with heart failure Table 4. Risk of reaching end point: Treatment improved clinical status, reduced the need for heart transplantation and was safe.
Study was stopped early. Treatment reduced sudden deaths and deaths from progressive pump failure. No improvement can beta blockers cause heart failure mortality. Information can beta blockers cause heart failure Waagstein F, Bristow MR, Swedberg K, Camerini F, Fowler MB, Silver MA, et al. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Metoprolol in Dilated Cardiomyopathy MDC Trial Study Group.
The Metoprolol in Dilated Cardiomyopathy MDC trial 19 was a multicenter, randomized, controlled trial designed to study the impact of metoprolol tartrate on a combined end point of death plus the need for heart transplantation in patients with idiopathic heart failure and NYHA class II and class III casino mobilnet. The risk of reaching this end point over 12 to 18 months can beta blockers cause heart failure At 12 months, the patients who received metoprolol tartrate had significant improvement in quality of life, ejection fraction and exercise capacity.
The two groups had no difference in all-cause mortality. All of the benefit in the primary end point came from a decrease in the need for heart transplantation. However, MERIT-HF was larger, included patients with ischemic as well as idiopathic heart failure, used metoprolol succinate controlled-release formulation and structured the end point to be just please click for source instead of the can beta blockers cause heart failure end point of mortality plus need for transplantation.
MERIT-HF was stopped early can beta blockers cause heart failure the absolute mortality rate was 7. The difference was statistically significant. The improvement in mortality applied to sudden deaths and deaths from progressive pump failure. Only 27 persons with congestive heart failure would need to be treated with metoprolol succinate for one year to prevent one death.
Carvedilol Coreg is a novel agent with antagonist activity against alpha 1beta 1 and beta 2 receptors, as well as some antioxidant activity. It is the only beta blocker labeled by the U. Food and Drug Administration FDA for the treatment of heart failure.
Carvedilol was tested in the U. Carvedilol Heart Failure Program, which consisted of four trials in patients stratified into mild, moderate or severe heart failure groups based on exercise capacity 1220 — 23 Table 5 Mortality was not a defined primary end point, but it was prospectively defined and monitored by the data safety monitoring board.
The trials were terminated early because of the statistically significant reduction in mortality can beta blockers cause heart failure patients treated with carvedilol compared with placebo. Information from Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure.
Carvedilol Heart Failure Study Group. N Engl J Med ; Only one of the carvedilol trials, the study of patients with mild heart failure, evaluated mortality as a primary end point.
The absolute mortality rate was 3. Although the magnitude of the benefit was large, the number of deaths was small and the follow-up was short term. The mortality benefit occurred in all subgroups. Treated patients also had a significant reduction in risk of hospitalization for a cardiovascular cause. The data safety monitoring committee stopped the trial early because of a large mortality benefit in the treatment group. Bucindolol Bextra is a nonselective beta-blocking agent with mild vasodilating properties.
It was recently tested in patients with heart failure as part of the Beta Blocker Evaluation Survival Trial BEST. The results of this trial are not can beta blockers cause heart failure available. BEST was designed to evaluate the mortality impact of bucindolol in patients with severe heart failure NYHA class III or IV resulting from idiopathic or ischemic cardiomyopathy. There also appears to have been a differential race effect, with treatment benefit occurring in nonblacks but no benefit and even potential harm occurring in black patients.
Bucindolol is not yet available for use in the United States. A meta-analysis of 15 smaller trials plus the MDC, CIBIS and carvedilol trials included 3, link. This article reviews the results of all major mortality trials published to date.
When the patients in MERIT-HF and CIBIS-II are added to those in the trials covered in the meta-analysis, approximately 10, patients with heart failure have been enrolled in trials involving beta blockers. The safety of beta blockers has been confirmed in all of the trials. The three large trials MERIT-HF, CIBIS-II and the U.
Carvedilol Heart Failure Program all demonstrated significant reductions in mortality, of a magnitude far exceeding that of even ACE inhibitors. To date, all published mortality trials have been placebo controlled. A major comparative trial of carvedilol versus metoprolol is currently being conducted.
Compelling evidence now exists to support the safety and efficacy of beta-blocker therapy in patients with heart failure. Guidance on the implementation of beta-blocker therapy in these patients is can beta blockers cause heart failure in the following sections. Beta blocker therapy is appropriate in patients with NYHA class II or class III symptoms resulting from left ventricular systolic dysfunction.
Unless contraindicated, beta blockers should be considered a mainstay of therapy in these patients to improve symptoms and mortality and to decrease hospitalizations. None of the trials described in this article tested the use of beta blockers in patients with NYHA class I disease.
Many asymptomatic patients with left ventricular dysfunction have had a myocardial infarction sometime in the past. Data on the administration of beta blockers subsequent to myocardial infarction are compelling enough to justify the use of these agents, if tolerated, in patients with NYHA class I disease.
Many of these patients have other click here conditions, such as hypertension or angina, for which beta blockers may also be indicated.
Can beta blockers cause heart failure Beta Blocker Warnings and Precautions
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Beta-blockers are some of the most effective medications for treating heart failure. While side effects and determining dosage can make their use difficult, abruptly.