Β-blockers In Patients Research Articles

Differences Between β-Blockers in Patients With Chronic Heart Failure and Chronic Obstructive Pulmonary Disease: A Randomized Crossover Trial

Abstract Abstract. Objectives. The purpose of this study was to determine the respiratory, hemodynamic, and clinical effects of switching between β1-selective and nonselective β-blockers in patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD). Background. Carvedilol, metoprolol succinate, and bisoprolol are established β-blockers for treating CHF. Whether differences in β-receptor specificities affect lung or vascular function in CHF patients, particularly those with coexistent COPD, remains incompletely characterized. Methods. A randomized, open-label, triple-crossover trial involving 51 patients receiving optimal therapy for CHF was conducted in two Australian teaching hospitals. Participants received each β-blocker, dose-matched, for 6 weeks before resuming their original β-blocker. Echocardiography, N-terminal pro-hormone brain natriuretic peptide (NT-ProBNP), central augmented pressure from pulse waveform analysis, respiratory function testing, 6-minute walk distance, and New York Heart Association (NYHA) functional class were assessed at each visit. Results. Of 51 patients with a mean age of 66±12 years; NYHA functional class I (n=6), II (n=29), or III (n=16); and left ventricular ejection fraction mean of 37%±10%, 35 had coexistent COPD. NT-ProBNP was significantly lower with carvedilol than with metoprolol or bisoprolol (mean, carvedilol 1001 [95% confidence interval (CI), 633–1367] ng/L; metoprolol 1371 [95% CI, 778–1964] ng/L; bisoprolol 1349 [95% CI, 782–1916] ng/L; P<.01), and returned to baseline level on resumption of the initial β-blocker. Central augmented pressure, a measure of pulsatile afterload, was lowest with carvedilol (carvedilol 9.9 [95% CI, 7.7–12.2] mm Hg; metoprolol 11.5 [95% CI, 9.3–13.8] mm Hg; bisoprolol 12.2 [95% CI, 9.6–14.7] mm Hg; P<.05). In patients with COPD, forced expiratory volume in 1 second (FEV1) was lowest with carvedilol and highest with bisoprolol (carvedilol 1.85 [95% CI, 1.67–2.03] l/s; metoprolol 1.94 [95% CI, 1.73–2.14] l/s; bisoprolol 2.0 [95% CI, 1.79–2.22] l/s; P<.001). The NYHA functional class, 6-minute walk distance, and left ventricular ejection fraction did not change. The β-blocker switches were well tolerated. Conclusions. Switching between β1-selective β-blockers and the nonselective β-blocker carvedilol is well tolerated but results in demonstrable changes in airway function, most marked in patients with COPD. Switching from β1-selective β-blockers to carvedilol causes short-term reduction of central augmented pressure and NT-ProBNP.—Jabbour A, Macdonald PS, Keogh AM, et al. Differences between β-blockers in patients with chronic heart failure and chronic obstructive pulmonary disease: a randomized crossover trial. J Am Coll Cardiol. 2010;55:1780-1787.

β-blockers and Their Mortality Benefits: Underprescribed in Heart Failure and Chronic Obstructive Pulmonary Disease

This article discusses the most recent insights into the actions of β-blockers on the heart and lungs, highlighting that β-blockers should have a place in the treatment of patients with chronic obstructive pulmonary disease (COPD), especially in those with coexisting cardiovascular disease or arterial hypertension. Practical studies clearly show underutilization of β-blockers in patients with heart failure and COPD, which seems to be caused by an unnecessary fear for adverse effects on the lungs, and the 'outdated' adverse effects mentioned on instruction leaflets.

Cardiovascular Effects of Cocaine

The use of cocaine has evolved from chewing the leaves of the Erythroxylon coca bush thousands of years ago, to purification of cocaine hydrochloride over 100 years ago and its use in tonics and elixirs (at one time in popular cola drinks), to insufflating and injecting the fine, white, water-soluble, powder form, to a smokable freebase form called “crack,” which became popular in the 1980s.1 In 2007, 2.1 million Americans had recent cocaine use; 1.6 million met criteria for cocaine dependence or abuse.1 Cocaine accounted for 31% of all visits to the emergency department related to drug misuse or abuse.1 From 1971 to 1987, the incidence of deaths caused by cocaine overdose increased 20-fold in Dade County, Florida.2 In a consecutive series of 233 emergency visits by cocaine-using patients, 56% presented with cardiovascular complaints, including 40% with chest pain.3 A minority of these patients have acute myocardial infarction (MI) (≈6%),4,–,7 and overall mortality is low (<1%).3,–,5,8,–,10 However, cocaine is associated with a number of cardiovascular diseases, including MI, heart failure, cardiomyopathies, arrhythmias, aortic dissection, and endocarditis. Identifying patients with acute disease is challenging. This review describes the relationship between cocaine and various cardiovascular diseases, as well as appropriate diagnostic evaluation and therapies. ### Molecular Cocaine stimulates the sympathetic nervous system by inhibiting catecholamine reuptake at sympathetic nerve terminals,11,12 stimulating central sympathetic outflow,11 and increasing the sensitivity of adrenergic nerve endings to norepinephrine (Figure 1).12 Cocaine also acts like a class I antiarrhythmic agent (local anesthetic) by blocking sodium and potassium channels, which depresses cardiovascular parameters.13 Of these 2 primary, opposing actions, enhanced sympathetic activity predominates at low cocaine doses, whereas the local anesthetic actions …

Nonselective β-blockers in patients with refractory ascites

Nonselective β-blockers are often used in patients with cirrhosis and esophageal varices to prevent variceal bleeding. A recent study has suggested that nonselective β-blockers promote more harm than benefit in patients who have cirrhosis and refractory ascites. The authors of the study suggest that these drugs should be contraindicated in these patients.

Digoxin

Digoxin

Overview of the methods and therapies for the primary prevention of variceal bleeding

Patients with cirrhosis develop varices at a rate of 5% per year, and a third of patients with high-risk varices will bleed. The mortality associated with variceal haemorrhage is typically 20%, and still exceeds that of myocardial infarction. Current options to prevent the first variceal bleed include noncardioselective β-blockers or variceal band ligation. In patients with medium-to-large esophageal varices, both therapies reduce the risk of bleeding by 50% or more. The choice of therapy should take into account patient choice and local availability; although for most patients drug therapy is the preferred first-line treatment. There has been recent interest in carvedilol, with promising initial data. Further studies are necessary before universal recommendation. There is no role for drug therapy in patients without varices, and the use of β-blockers for patients with small varices is controversial.

Dogma Challenged — β-Blockers for Patients with Cocaine-Associated Chest Pain?

Despite the proven survival benefit of β-blockers in patients with myocardial infarction, traditional teaching and current guidelines dictate that they

The Role of Vasodilating β-Blockers in Patients with Hypertension and the Cardiometabolic Syndrome

In the United States, a vast segment of the adult population is classified as having the cardiometabolic syndrome, and currently there are epidemic rates of both type 2 diabetes mellitus and obesity. Hypertension is closely linked with these metabolic disorders and is a strong independent predictor of incident type 2 diabetes. In addition, hypertension is an important contributor to increasing cardiovascular disease risk in patients with the cardiometabolic syndrome. Lowering elevated blood pressure in patients with the cardiometabolic syndrome or diabetes is a critical component of reducing global cardiovascular risk. However, aggressive management of hypertension in these patients is often challenging, and the presence of these conditions is associated with poor blood pressure control. The utility of β-blockers in patients with these conditions continues to be a subject of intense debate, given the adverse metabolic effects associated with conventional β-blockers. Data on vasodilating β-blockers, however, suggest that these agents have favorable or neutral metabolic effects and generally more favorable effects when compared with nonvasodilating members of this class. These agents may expand the utility of β-blockers to patient populations traditionally considered not to be optimal candidates for β-blocker therapy—a fact which has important clinical implications, because more antihypertensive agents are needed to diversify the therapeutic options available for clinicians treating hypertension in patients with the cardiometabolic syndrome or type 2 diabetes.

The Role of Vasodilating β-Blockers in Patients with Complicated Hypertension: Focus on Nebivolol

Despite their proven mortality and morbidity outcomes benefits, β-blockers remain substantially underused in patients with cardiac conditions. Reluctance to prescribe β-blockers may be owing to concerns about tolerability with the traditional drugs in this class. β-Blockers with vasodilatory properties, such as carvedilol and nebivolol, may overcome the tolerability and metabolic issues associated with traditional β-blockers. Because endothelial dysfunction, the pathophysiologic hallmark of hypertension, may be heightened in populations with difficult-to-treat hypertension (e.g., elderly patients, African American patients), a vasodilating β-blocker may be a particularly appropriate choice for these patient groups.

Interest of β-blockers in patients with right ventricular systemic dysfunction

β-blockers improve the prognosis of patients with cardiac failure due to left ventricular systolic dysfunction. The aim of this study was to assess the efficacy of β-blockers in patients with dysfunctional systemic right ventricle. Fourteen patients with systemic right ventricle following a Mustard or a Senning operation for the transposition of the great arteries, or congenitally corrected transposition were included in the study. All had a decreased systemic right ventricular ejection fraction despite having standard cardiac failure therapy. Quality of life, New York Heart Association class, aerobic capacity, and systemic right ventricular function were assessed before treatment with β-blockers and at the end of the follow-up period, mean of 12.8 months with a range from 3 to 36 months. Change in New York Heart Association class was significant (p = 0.016). Quality of life improved significantly throughout the study from a median grade 2 with a range from 1 to 3 to a median grade 1 with a range from 1 to 2 (p = 0.008). Systemic right ventricular ejection fraction assessed by radionuclide ventriculography improved significantly from a median of 41% (range: 29-53%) to 49% (range: 29-62%; p = 0.031). However, the change in thee ejection fraction assessed by magnetic resonance imaging was not significant from a median of 29% (range: 12-47%) to 32% (range: 22-63%; p = 0.063). In patients with cardiac failure due to systemic right ventricular dysfunction, β-blockers improve New York Heart Association class, quality of life, and systemic right ventricular ejection fraction assessed by radionuclide ventriculography.

Heart Rate Control in an Unselected Consecutive Population of Outpatients With Stable Coronary Artery Disease: Analysis of the CARDIf Study Cohort

Despite increasing pharmacological and mechanical treatment options, coronary artery disease (CAD) continues to be associated with considerable mortality and morbidity. The detrimental effects of elevated heart rate (HR) on cardiac morbidity and mortality are well established. Although β-blockers represent the mainstay of treatment of patients with CAD and heart failure (HF), according to current guidelines, these drugs are most often undertitrated for various reasons despite the lack of real contraindications. This observational, cross-sectional, multicenter survey was designed to assess which clinical variables influence HR and whether HR is adequately controlled; and the rate of administration of β-blockers in patients with chronic CAD attending outpatient clinics. Over 6 months 2226 (of 2362 screened) outpatients with stable CAD and resting HR > 60 beats/min (bpm) were enrolled. Left ventricular systolic function was not a criterion of inclusion. Each patient had a full clinical examination and the past medical history, angina, or HF-related symptoms were evaluated. In each patient, the demographics and cardiovascular risk factors were assessed; weight, height, and body mass index (BMI) was calculated; sitting blood pressure and a HR by a 12-lead electrocardiogram was obtained. Overall, 45.4% of patients with CAD were not under β-blocker therapy. Male patients featured a significantly lower HR than females, corrected from β-blockers use. In multiple regression analysis, which also included the use/nonuse of β-blockers as independent variable, not using β-blockers, female sex (OR 2.55), New York Heart Association (NYHA) classes I and II (OR 1.62 vs classes III-IV), smoking (OR 0.89), and increased BMI (OR 0.14) were all independent determinants of resting HR, with the lack of β-blockade therapy (OR 3.35) being the main determinant of the magnitude of HR increase. Heart rate in patients under β-blocker therapy was significantly less than in untreated patients (73.6 ± 10.0 vs 77.1 ± 10.4, P < .0001), although it often did not reach target values of <70 bpm. Among patients with HF symptoms, 56.6% were under β-blocker therapy. In patients free of symptoms of HF, HR was significantly less in those receiving a β-blocker (72.3 ± 10 vs 76.7 ± 11 bpm, P < .0001). This survey demonstrates that HR is poorly controlled in a broadly representative cohort of outpatients with CAD, even in those on β-blocker therapy, mainly because of undertitration of therapy-almost half of the patients with CAD and elevated resting HR are not on β-blockers. This might be related to absolute or relative controindications and to haemodynamic and chronotropic intolerance to beta-blockers.

β-Blocker Therapy and Mortality of Patients With Chagas Cardiomyopathy

Background— Peculiar aspects of Chagas cardiomyopathy raise concerns about efficacy and safety of sympathetic blockade. We studied the influence of β-blockers in patients with Chagas cardiomyopathy. Methods and Results— We examined REMADHE trial and grouped patients according to etiology (Chagas versus non-Chagas) and β-blocker therapy. Primary end point was all-cause mortality or heart transplantation. Altogether 456 patients were studied; 27 (5.9%) were submitted to heart transplantation and 202 (44.3%) died. Chagas etiology was present in 68 (14.9%) patients; they had lower body mass index (24.1±4.1 versus 26.3±5.1, P =0.001), smaller end-diastolic left ventricle diameter (6.7±1.0 mm versus 7.0±0.9 mm, P =0.001), smaller proportion of β-blocker therapy (35.8% versus 68%, P &lt;0.001), and higher proportion of spironolactone therapy (74.6% versus 57.8%, P =0.003). Twenty-four (35.8%) patients with Chagas disease were under β-blocker therapy and had lower serum sodium (136.6±3.1 versus 138.4±3.1 mEqs, P =0.05) and lower body mass index (22.5±3.3 versus 24.9±4.3, P =0.03) compared with those who received β-blockers. Survival was lower in patients with Chagas heart disease as compared with other etiologies. When only patients under β-blockers were considered, the survival of patients with Chagas disease was similar to that of other etiologies. The survival of patients with β-blockers was higher than that of patients without β-blockers. In Cox regression model, left ventricle end-diastolic diameter (hazard ratio, 1.78; CI, 1.15 to 2.76; P =0.009) and β-blockers (hazard ratio, 0.37; CI, 0.14 to 0.97; P =0.044) were associated with better survival. Conclusions— Our study suggests that β-blockers may have beneficial effects on survival of patients with heart failure and Chagas heart disease and warrants further investigation in a prospective, randomized trial. Clinical Trial Registration— clinicaltrials.gov. Identifier: NCT00505050.

Is it Time to Discard β-Blockers in Patients Undergoing Noncardiac Surgery?

Prevention of cardiac complications in patients undergoing major surgical or vascular procedures should be approached as the prevention of these complications in other common situations. beta-Adrenoceptor antagonists (beta-blockers) should be indicated in patients who are candidates for those treatments, regardless of whether surgery is performed. Current guidelines include patients with acute coronary syndrome, systolic dysfunction, chronic coronary artery disease (CAD), vascular disease, and diabetes as candidates for long-term beta-blocker therapy. Therefore risk stratification prior to surgery is indeed required to identify patients with existing CAD or myocardial ischemia in order to be able to treat them as such. In addition, beta-blockers may reduce ischemic complications in high-risk patients. However, initiating treatment at high dosages immediately before surgery has been associated with an increased risk of hypotensive strokes.

Is Pretreatment with Beta-Blockers Beneficial in Patients with Acute Coronary Syndrome?

Objectives: The role of β-blockers in the treatment of hypertension is discussed controversially and the data showing a clear benefit in acute coronary syndromes (ACS) were obtained in the thrombolysis era. The goal of this study was to analyze the role of pretreatment with β-blockers in patients with ACS. Methods: Using data from the Acute Myocardial Infarction in Switzerland (AMIS Plus) registry, we analyzed outcomes of patients with β-blocker pretreatment in whom they were continued during hospitalization (group A), those without β-blocker pretreatment but with administration after admission (group B) and those who never received them (group C). Major adverse cardiac events defined as composed endpoint of re-infarction and stroke (during hospitalization) and/or in-hospital death were compared between the groups. Results: A total of 24,709 patients were included in the study (6,234 in group A, 12,344 in group B, 6,131 in group C). Patients of group B were younger compared to patients of group A and C (62.5, 67.6 and 68.4, respectively). In the multivariate analysis, odds ratio for major adverse cardiac events was 0.59 (CI 0.47–0.74) for group A and 0.66 (CI 0.55–0.83) for group B, while group C was taken as a reference. Conclusions: β-Blocker therapy is beneficial in ACS and they should be started in those who are not pretreated and continued in stable patients who had been on chronic β-blocker therapy before.

Medication Underuse During Long-Term Follow-Up in Patients With Peripheral Arterial Disease

Patients with peripheral arterial disease constitute a high-risk population. Guideline-recommended medical therapy use is therefore of utmost importance. The aims of our study were to establish the patterns of guideline-recommended medication use in patients with PAD at the time of vascular surgery and after 3 years of follow up, and to evaluate the effect of these therapies on long-term mortality in this patient group. Data on 711 consecutive patients with peripheral arterial disease undergoing vascular surgery were collected from 11 hospitals in the Netherlands (enrollment between May and December 2004). After 3.1+/-0.1 years of follow-up, information on medication use was obtained by a questionnaire (n=465; 84% response rate among survivors). Guideline-recommended medical therapy use for the combination of aspirin and statins in all patients and beta-blockers in patients with ischemic heart disease was 41% in the perioperative period. The use of perioperative evidence-based medication was associated with a reduction of 3-year mortality after adjustment for clinical characteristics (hazard ratio, 0.65; 95% CI, 0.45 to 0.94). After 3 years of follow-up, aspirin was used in 74%, statins in 69%, and beta-blockers in 54% of the patients respectively. Guideline-recommended medical therapy use for the combination of aspirin, statins, and beta-blockers was 50%. The use of guideline recommended therapies in the perioperative period was associated with reduction in long-term mortality in patients with peripheral arterial disease. However, the proportion of patients receiving these evidence-based treatments-both at baseline and 3 years after vascular surgery-was lower than expected based on the current guidelines. These data highlight a clear opportunity to improve the quality of care in this high-risk group of patients.

Quality Improvement

Outcomes research examines the effects of healthcare interventions and policies on health outcomes for individual patients and populations in routine practice, as opposed to the idealized setting of clinical trials. A national survey from 1998 to 2000 that evaluated the extent to which patients received established processes of care for 30 medical conditions illustrated the importance of outcomes research.1 Among adults living in 12 metropolitan areas in the United States, only half of patients received proven elements of preventive care, treatments for acute illness, and chronic disease management for which they were eligible. For cardiovascular conditions, the use of proven therapies varied widely from 68% to 25% of patients who received recommended care for coronary artery disease and atrial fibrillation, respectively.1 Despite these gaps between ideal and actual care, patient outcomes have improved in many fields. For instance, the age-adjusted mortality from cardiovascular disease in the United States fell by >40% from 1980 to 2000 as a result of improvements in risk factor modification and uptake of evidence-based treatments for coronary artery disease, myocardial infarction, and heart failure.2,3 Nevertheless, many Americans do not receive the ideal recommended care (either at all or in a timely fashion), whereas others receive too much or the wrong care.4,5 In the field of cardiovascular diseases, substantial opportunities for improvement remain. Outcomes research has generated a foundation of knowledge about what constitutes ideal care and what gaps exist between ideal and actual care, but we have less understanding about how to deliver this ideal care to every patient every day. The potential for basic science breakthroughs to reach and improve the health of individual patients and populations may be substantially delayed or may not be realized if science is not efficiently translated to action. Moreover, in many cases, increased delivery of …

Should nephrologists use beta-blockers? A perspective

Given the high prevalence of cardiovascular disease in people with chronic kidney disease (CKD) and the clear benefits of mortality reduction observed for most β−blockers in clinical trials, they are relatively underused in CKD patients [1,2]. The rationale for use of β-blockers in patients with CKD is reviewed in detail elsewhere [2,3] but is summarized in this editorial. Alterations in β- and α-receptor responsiveness are associated with sympathetic over-activity in CKD. This increased sympathetic activity is involved in the genesis of hypertension, and contributes to cardiac complications seen in CKD [2,3]. The contribution of the sympathetic nervous system to nephropathy progression is documented in sub-totally nephrectomized rats where non-hypotensive doses of β-blockers ameliorate development of glomerulosclerosis and cardiac injury [4]. In men, sympathetic over-activity, as assessed by sural nerve microneurography, was present in patients on haemodialysis [5], stage 4 nephropathy [6] and in early stage 2 nephropathy among patients with polycystic kidney disease [7]. The role of the damaged kidney in causing sympathetic over-activity is illustrated by normalization of sympathetic over-activity in haemodialysis patients following bilateral nephrectomy [5] and in renal allograft recipients when their shrunken native kidneys are removed [8]. The most common cause of death in stage 3 and higher CKD results from complications of cardiovascular disease. This may be due, in part, to inadequate treatment of blood pressure, where blood pressure goals were not attained and agents known to reduce mortality secondary to cardiovascular causes, i.e. aspirin, ACE inhibitors and β-blockers were not used [9]. In a separate study, β-blockers were used in fewer than 30% of haemodialysis patients [10]. This is surprising, since β-blockers are well-established, evidence-based therapy for reducing cardiovascular risk in hypertension associated with diabetes and after myocardial infarction [11,12]. Observational studies support definite survival benefits derived from β-blocker use in patients with advanced CKD [13,14]. Furthermore, a prospective,

Impact of Cardioselective β-Blockers on Mortality in Patients with Chronic Obstructive Pulmonary Disease and Atherosclerosis

beta-Blocker use is associated with improved health outcomes in patients with cardiovascular disease. There is a general reluctance to prescribe beta-blockers in patients with chronic obstructive pulmonary disease (COPD) because they may worsen symptoms. We investigated the relationship between cardioselective beta-blockers and mortality in patients with COPD undergoing major vascular surgery. We evaluated 3,371 consecutive patients who underwent major vascular surgery at one academic institution between 1990 and 2006. The patients were divided into those with and without COPD on the basis of symptoms and spirometry. The major endpoints were 30-day and long-term mortality after vascular surgery. Patients were defined as receiving low-dose therapy if the dosage was less than 25% of the maximum recommended therapeutic dose; dosages higher than this were defined as intensified dose. There were 1,205 (39%) patients with COPD of whom 462 (37%) received cardioselective beta-blocking agents. beta-Blocker use was associated independently with lower 30-day (odds ratio, 0.37; 95% confidence interval, 0.19-0.72) and long-term mortality in patients with COPD (hazards ratio, 0.73; 95% confidence interval, 0.60-0.88). Intensified dose was associated with both reduced 30-day and long-term mortality in patients with COPD, whereas low dose was not. Cardioselective beta-blockers were associated with reduced mortality in patients with COPD undergoing vascular surgery. In carefully selected patients with COPD, the use of cardioselective beta-blockers appears to be safe and associated with reduced mortality.

Statin Therapy within the Perioperative Period

STATINS are highly effective in lowering serum cholesterol concentrations through 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibition and thus are central to the primary and secondary prevention of cardiovascular disease. More than 50% of patients undergoing major vascular surgery and 80% undergoing cardiac surgery are on chronic statin therapy. 1,2 Statins also exert numerous lipid-independent or “pleiotropic” effects (effects that were not expected during drug development) as a result of their ability to inhibit the inflammatory response, reduce thrombosis, enhance fibrinolysis, decrease platelet reactivity, inhibit cell growth, reduce ischemia–reperfusion injury, and restore endothelial function. These beneficial effects result predominantly from the modulation of the complex interplay between the pathologic triad of inflammation, dynamic obstruction, and thrombosis. 3 This triad is integral to the surgical stress response and central to postoperative outcomes. However, recent reports noted that patients who undergo postoperative statin withdrawal experience increased cardiac morbidity when compared with patients who undergo early postoperative readministration of statins or with patients not treated with statins. 1,4 These facts raise several important questions for the anesthesiologist regarding statin therapy during the perioperative period: (1) Do statins modify perioperative risk? (2) Is continuation or discontinuation of statin therapy during the perioperative period associated with additional risk? (3) Do the potential benefits of statin therapy outweigh the potential risks? This review of the literature explores the risks and benefits associated with perioperative statin therapy.

β1-adrenoceptor polymorphisms: deviation of clinical outcome with use of β-blockers in ventricular dysfunction

While the debate continues regarding the role of polymorphisms of β1-adrenoceptors on the clinical outcomes and beneficial effects of β-blockers in patients with heart failure, we need to step back and examine the evidence in the peer-reviewed literature more closely.