Use of beta-blockers in older adults with chronic heart failure

Most heart failure patients are older adults. Angiotensin-converting enzyme (ACE) inhibitors reduce mortality and morbidity in patients with systolic heart failure. However, the annual mortality rate in patients with systolic heart failure receiving ACE inhibitors is about 12%. Beta-blockers further reduce mortality rate by an additional 35% to 65%. Because of potential adverse effects, the rate of beta-blocker use is likely to be low in older adults with systolic heart failure. In this article, we review the findings of the major beta-blocker trials in systolic heart failure and discuss the potential benefits and adverse effects of beta-blockers, along with various practical aspects of their use in older adults with systolic heart failure. Subgroup analyses of these trials suggest that the survival benefits of beta-blockers observed in the main trials are also observed in persons 65 years of age and older. However, data are limited for heart failure patients 85 years of age and older. About half of the older adults with heart failure do not have systolic heart failure, and currently there is no evidence that beta-blockers also improve survival in these patients. Beta-blockers might play a beneficial role in heart failure patients without systolic heart failure by reducing high blood pressure, high heart rate, or myocardial ischemia, conditions known to impair ventricular relaxation. Adequate knowledge of the commonly used beta-blockers, along with careful patient selection and close monitoring for adverse effects will allow safe initiation and continuation of beta-blocker use for older adults with systolic heart failure. It is likely that lower doses of beta-blockers are as effective as higher doses.     

Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race,gender, and diabetic status: a meta-analysis of major clinical trials

OBJECTIVES: This study sought to assess the effect of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers on all-cause mortality in patients with left ventricular (LV) systolic dysfunction according to gender, race, and the presence of diabetes. BACKGROUND: Major randomized clinical trials have established that ACE inhibitors and beta-blockers have life-saving benefits in patients with LV systolic dysfunction. Most patients enrolled in these trials were Caucasian men. Whether an equal effect is achieved in women, non-Caucasians, and patients with major comorbidities has not been established. METHODS: The authors performed a meta-analysis of published and individual patient data from the 12 largest randomized clinical trials of ACE inhibitors and beta-blockers to produce random effects estimates of mortality for subgroups. RESULTS: Data support beneficial reductions in all-cause mortality for the use of beta-blockers in men and women, the use of ACE inhibitors and some beta-blockers in black and white patients, and the use of ACE inhibitors and beta-blockers in patients with or without diabetes. Women with symptomatic LV systolic dysfunction probably benefit from ACE inhibitors, but women with asymptomatic LV systolic dysfunction may not have reduced mortality when treated with ACE inhibitors (pooled relative risk = 0.96; 95% confidence interval: 0.75 to 1.22). The pooled estimate of three beta-blocker studies supports a beneficial effect in black patients with heart failure, but one study assessing bucindolol reported a nonsignificant increase in mortality. CONCLUSIONS: Angiotensin-converting enzyme inhibitors and beta-blockers provide life-saving benefits in most of the subpopulations assessed. Women with asymptomatic LV systolic dysfunction may not achieve a mortality benefit when treated with ACE inhibitors.     

Update on recent clinical trials in congestive heart failure

Understanding of the pathophysiology of heart failure has advanced over the last decade, resulting in new therapeutic advances. Convincing data exist that angiotensin-converting enzyme (ACE) inhibition and adrenergic blockade are the most important therapies and have the capacity to improve survival and lower morbidity. Higher doses of both ACE inhibitors and beta-blockers appear to provide additional benefits. The aldosterone antagonist spironolactone, when used in severe heart failure, provides additional survival advantage when added to standard triple therapy. Angiotensin receptor blockers have not been shown to be superior to ACE inhibitors, and their role in heart failure treatment requires further investigation. No trial's data support the use of inotropic agents or calcium channel blockers in heart failure. A number of new therapeutic agents, including vasopressin antagonists and tumor necrosis factor-alpha receptor antibody are in phase II and III clinical trials. If proved beneficial, they may provide new treatment options for patients with heart failure. Nevertheless, the current challenge is to increase the use of proven therapies, namely ACE inhibitors and beta-blockers, to improve outcomes in the rapidly growing population of patients with congestive heart failure.     

beta-blocker therapy in patients after aortic valve replacement for aortic regurgitation

Background: beta-blocker therapy for dilated or ischemic cardiomyopathy is now an accepted and effective treatment. However, little is known about its efficacy in patients with postoperative impaired left ventricular function. This retrospective study was designed to assess the effects of beta-blocker therapy in patients after aortic valve replacement (AVR) for aortic regurgitation (AR). Methods: A total of 59 patients who underwent AVR for chronic AR were assigned to four groups. Twelve patients were treated with both ACE inhibitors and beta-blockers, 12 patients with only ACE inhibitors, eight patients with only beta-blockers, and 27 patients without beta-blockers or ACE inhibitors. A postoperative echocardiographic study was performed one year after surgery. Results: The heart rate was significantly reduced in patients with beta-blockers despite the use of ACE inhibitors after surgery. Postoperative left ventricular volume was more significantly decreased in beta patients than in non-beta patients despite the use of ACE inhibitors. There were also significant reductions in left ventricular mass index in ACE+beta patients compared to ACE+non-beta patients. However, there were no significant differences in NYHA functional class and survival rate between beta patients and non-beta patients. Conclusions: beta-blocker therapy may improve cardiac performance by reducing cardiac volume and mass in patients with impaired LV function after AVR for AR.     

Is heart rate reduction more important than target dose in chronic heart failure therapy with a beta-blocker?

1 IntroductionBeta-adrenoceptor blocking agents (beta-blockers) are now well established as cornerstone therapy in patients with systolic chronic heart failure (CHF).[1] Clinical data have overwhelmingly proven the beneficial effects of beta-blocker therapy in terms of improving patient prognosis,decreasing requirements for hospitalization,and postponing disease progression.[2-4] However,it remains unclear what the optimal efficacious and safe dose for an individual patient with CHF is,and whether this can simply be inferred from the target dose for each beta-blocking agent as used in the major clinical trials.Beta-blockers are a heterogeneous class of drugs,and due to the polymorphisms of beta-adrenoceptor gene expression,there is marked individual variation in responsiveness to specific agents.[5] If pharmacodynamic markers of responsiveness to beta-blockade (such as heart rate (HR) reduction) are more important than the achievement of a target dose,could they become another potential therapeutic target in beta-blocker therapy? We provide a discussion of the question in this article.     

New Information on the Role of Beta-Blockers in Cardiac Therapy

Summary. Hypertension and ischemic heart disease are important precursors of heart failure. The prevention of progression to heart failure is a prime objective when treating patients with hypertension or ischemic heart disease. In patients with hypertension, treatment with either diuretics or beta-blockers reduces the risk of chronic heart failure. In patients with ischemic heart disease, beta-blocker therapy reduces the risk of recurrent myocardial infarction and ensuing cardiac dysfunction. The beneficial effects of beta-blocker therapy may be greater in post-infarction patients who have impaired left ventricular function than in those patients without such impairment.When considering heart failure itself, the efficacy of angiotensin-converting enzyme (ACE) inhibitors has been demonstrated in patients with mild-to-severe left ventricular dysfunction and their use is indicated for all stages of heart failure to reduce symptoms and retard further impairment of left ventricular function. Diuretics and digitalis offer relief from the symptoms of the disease, while positive inotropes are reserved for parenteral administration in end-stage heart failure, as a bridge to transplantation, or in acute exacerbations of the disease. Added to standard therapy, beta-blockade is of value in the treatment of heart failure, preventing further deterioration and improving hemodynamics, exercise tolerance, quality of life, and long-term prognosis.     

Comparison of various blood pressure lowering treatments on the primary prevention of cardiovascular outcomes in recent randomised clinical trials

Randomised clinical trials completed over the past 8 to 10 years have provided much new evidence regarding the cardiovascular risks and benefits of treatment with newer blood pressure lowering drugs, particularly ACE inhibitors and calcium channel blockers (CCB). Trials of active treatment against placebo have now established that ACE inhibitors and CCBs reduce the risk of coronary heat disease and stroke in subjects with elevated blood pressure and that ACE inhibitors reduce the risk of heart failure but calcium antagonists do not. Clinical trials comparing active treatment regimens based on different blood pressure lowering drug classes, have provided convincing evidence that ACE inhibitors, CCBs, and "conventional treatment" with diuretics/beta-blockers are equally effective in the primary prevention of coronary heart disease, but that minor differences of the order of 5-12% favouring calcium antagonists may exist. The one area with a major difference is again for the primary prevention of heart failure where calcium antagonists are clearly inferior to diuretics/ beta-blockers and to ACE inhibitors. There is now convincing evidence that blood pressure lowering is effective in the secondary prevention of cardiovascular outcomes in subjects with established coronary heart disease, cerebrovascular disease, diabetes and chronic kidney disease, especially diabetic nephropathy. Clinical trial evidence comprising regimens based on different drug classes for the secondary prevention of cardiovascular outcomes is still very limited. It is possible that longer differences will be found between the efficacy and safety of drugs in secondary prevention than have been reported so far in primary prevention.     

Beta-blockers in congestive heart failure. A Bayesian meta-analysis

PURPOSE: Congestive heart failure is an important cause of patient morbidity and mortality. Although several randomized clinical trials have compared beta-blockers with placebo for treatment of congestive heart failure, a meta-analysis quantifying the effect on mortality and morbidity has not been performed recently. DATA SOURCES: The MEDLINE, Cochrane, and Web of Science electronic databases were searched from 1966 to July 2000. References were also identified from bibliographies of pertinent articles. STUDY SELECTION: All randomized clinical trials of beta-blockers versus placebo in chronic stable congestive heart failure were included. DATA EXTRACTION: A specified protocol was followed to extract data on patient characteristics, beta-blocker used, overall mortality, hospitalizations for congestive heart failure, and study quality. DATA SYNTHESIS: A hierarchical random-effects model was used to synthesize the results. A total of 22 trials involving 10 135 patients were identified. There were 624 deaths among 4862 patients randomly assigned to placebo and 444 deaths among 5273 patients assigned to beta-blocker therapy. In these groups, 754 and 540 patients, respectively, required hospitalization for congestive heart failure. The probability that beta-blocker therapy reduced total mortality and hospitalizations for congestive heart failure was almost 100%. The best estimates of these advantages are 3.8 lives saved and 4 fewer hospitalizations per 100 patients treated in the first year after therapy. The probability that these benefits are clinically significant (>2 lives saved or >2 fewer hospitalizations per 100 patients treated) is 99%. Both selective and nonselective agents produced these salutary effects. The results are robust to any reasonable publication bias. CONCLUSIONS: beta-Blocker therapy is associated with clinically meaningful reductions in mortality and morbidity in patients with stable congestive heart failure and should be routinely offered to all patients similar to those included in trials.     

A continued role for beta-blocker therapy in heart failure

The number of patients with newly diagnosed heart failure continues to grow worldwide, to some extent reflecting the increase in survival after acute coronary syndromes and the aging of the population. The search for new and effective therapies for this condition remains a priority in the 21st century. The use of beta-blockers is now well established in the clinical context of mild and moderate systolic heart failure. The effects of beta-blockade on mortality are additive to those with angiotensin-converting enzyme inhibitor therapy. Recently completed, large, randomized trials provided strong evidence for the use of beta-blockers in severe (NYHA functional class IV) heart failure and in asymptomatic patients with left ventricular systolic dysfunction and recent myocardial infarction. Obviously, patient selection still remains the key to the safe use of beta-blockers in patients with heart failure. Further data from clinical trials have emerged to support similar benefits in terms of mortality and morbidity, a good safety record, and tolerability in patients at extremes of age (children and adults >70 years of age) and in specific clinical circumstances (including diabetes, chronic obstructive airways disease, renal failure, and atrial fibrillation). Recent use of beta-blockers with vasodilatory properties in patients with heart failure and preserved systolic function (so-called diastolic heart failure) appears promising but will require large-scale, long-term trials prior to widespread clinical use.     

Beta-blocker therapy in heart failure in the elderly

Chronic heart failure (CHF) is a common and disabling condition with morbidity and mortality that increase dramatically with advancing age. There is some evidence available about beta-blocker therapy in the elderly. The Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure (SENIORS) and retrospective subgroup (elderly) analyses of landmark clinical trials in stable systolic heart failure have provided data supporting the use of beta-blocker as baseline therapy in heart failure in the elderly. However, beta-blocker is still less frequently used in elderly compared to younger patients. There are many reasons, one of which is that available data on elderly patients are not as convincing as those pertaining to their younger counterparts. There is uncertainty or disagreement about whether beta-blockers are equally beneficial and well tolerated in elderly heart failure patients as in younger ones. In other words, the level of evidence regarding beta-blocker therapy in the elderly is not regarded as high as that in younger patients. Indeed, the senior heart failure population, which in fact comprises the majority of all heart failure patients, is in general less well studied, both experimentally and clinically, than younger populations. Both clinical studies and experience indicate good tolerability in the use of beta-blocker in the elderly. Although beta-blockers are well tolerated by the elderly, target doses (based on previous clinical trials) may be difficult to achieve. The question is whether we should use the same target dose in the elderly as that in younger patients. Theoretically, the most effective dose is the highest dose tolerated, which may differ across different age groups. Is it time to abandon the "target dose" for the "highest dose tolerated"? The time has come to carry out active research to achieve better documentation of evidence based heart failure management in the elderly for the benefit of a large number of elderly patients with heart failure. We need clinical trial data that show definite improvement in outcomes as well as a clear-cut, favourable benefit-risk analysis involving beta-blockers in typical older heart failure patients irrespective of comorbidity and polypharmacy. Until the above is available, it may be wiser to adhere to beta-blocker therapy, which at present is better documented than other heart failure therapies in the elderly.     

Additive Beneficial Effects of Beta-Blockers to Angiotensin-Converting Enzyme Inhibitors in the Survival and Ventricular Enlargement (SAVE) Study

Objectives. This study assessed whether treatment with a beta-adrenergic blocking agent in addition to the use of the angiotensin-converting enzyme (ACE) inhibitor captopril decreases cardiovascular mortality and morbidity in patients with asymptomatic left ventricular dysfunction after myocardial infarction (MI) and whether the presence of neurohumoral activation at the time of hospital discharge predicts the effects of beta-blocker treatment in these patients.Background. Both beta-blockers and ACE inhibitors have been shown to have beneficial effects in patients with left ventricular dysfunction but no overt heart failure after MI. These patients often have persistent neurohumoral activation at the time of hospital discharge, and one would expect that patients with activation of the sympathetic nervous system derive the most benefit from treatment with beta-blockers. However, beta-blockers are underutilized in this high risk group of patients, and it is unknown whether their beneficial effects are additive to those of ACE inhibitors.Methods. We performed a retrospective analysis of data from the Survival and Ventricular Enlargement (SAVE) study and its neurohumoral substudy. The relations between beta-blocker use at the time of randomization and neurohumoral activation and the subsequent development of cardiovascular events were analyzed by use of Cox proportional hazards models controlling for covariates.Results. After adjustment for baseline imbalances, beta-blocker use was associated with a significant reduction in risk of cardiovascular death (30%, 95% confidence interval [CI] 12% to 44%) and development of heart failure (21%, 95% CI 3% to 36%), but the reduction in recurrent MI (11%, 95% CI 13% to 31%) was not significant. These reductions were independent of the use of captopril. Beta-blockers were not found to have a greater effect in patients with neurohumoral activation at the time of hospital discharge.Conclusions. The beneficial effects of beta-blocker use at the time of hospital discharge in patients with asymptomatic left ventricular dysfunction after MI appear to be additive to those of captopril and other interventions known to improve prognosis. Neurohumoral activation at the time of hospital discharge fails to identify those patients who will derive the greatest benefit from treatment with beta-blockers.(J Am Coll Cardiol 1997;29:229–36)     

Role of Beta-Blocker Therapy in Heart Failure and Atrial Fibrillation

Heart failure is a serious disorder associated with substantial morbidity and mortality. Approximately 15-30% patients with systolic heart failure are in atrial fibrillation and the proportion increases with severity of heart failure. Patients with heart failure and atrial fibrillation have worse outcome than those in sinus rhythm. Beta-blockers, together with angiotensin-converting enzymes inhibitors, are the standard therapy in patients with chronic heart failure. Retrospective studies have suggested that despite the improvement in left ventricular systolic function after treatment with beta-blockers, the exercise capacity and symptoms in those heart failure patients with atrial fibrillation was not improved as much as those in sinus rhythm. Moreover, the use of bisoprolol in the Cardiac Insufficiency Bisoprolol Study II, unlike those in sinus rhythm, failed to produce any survival benefit in patients with poor systolic function and atrial fibrillation. It seems that those patients with heart failure and atrial fibrillation may have different response to beta-blocker therapy. Prospective trials to clarify the impact of beta-blocker therapy and the optimal therapeutic strategy in this high-risk group of patients are warranted.     

Practical recommendations for the use of ACE inhibitors, beta-blockers, aldosterone antagonists and angiotensin receptor blockers in heart failure: putting guidelines into practice

Surveys of prescribing patterns in both hospitals and primary care have usually shown delays in translating the evidence from clinical trials of pharmacological agents into clinical practice, thereby denying patients with heart failure (HF) the benefits of drug treatments proven to improve well-being and prolong life. This may be due to unfamiliarity with the evidence-base for these therapies, the clinical guidelines recommending the use of these treatments or both, as well as concerns regarding adverse events. ACE inhibitors have long been the cornerstone of therapy for systolic HF irrespective of aetiology. Recent trials have now shown that treatment with beta-blockers, aldosterone antagonists and angiotensin receptor blockers also leads to substantial improvements in outcome. In order to accelerate the safe uptake of these treatments and to ensure that all eligible patients receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of HF. The objective of these recommendations is to provide practical guidance for non-specialists, in order to increase the use of evidenced based therapy for HF. These practical recommendations are meant to serve as a supplement to, rather than replacement of, existing HF guidelines.     

Sudden Cardiac Death in Dilated Cardiomyopathy – Therapeutic Options

BACKGROUND: Despite routine use of angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and spironolactone in patients with heart failure due to dilated cardiomyopathy (DCM), these patients still have a considerable annual mortality rate of 5-10%. Sudden unexpected death accounts for up to 50% of all deaths and is most often due to rapid ventricular tachycardia or ventricular fibrillation and less often due to bradyarrhythmias or asystole. THERAPEUTIC OPTIONS: The use of beta-blockers in patients with heart failure has been shown to improve overall mortality considerably. This survival benefit has been demonstrated for bisoprolol, metoprolol and carvedilol. Therefore, one of these three beta-blocking agents should be administered routinely starting with low doses in all patients with New York Heart Association (NYHA) class II or III heart failure in addition to ACE inhibitors, unless there is a contraindication to beta-blocker use. In addition, NYHA class IV heart failure patients have been shown to benefit from carvedilol therapy, if tolerated. The conflicting results of GESICA and CHF-STAT studies do not support a strategy of "prophylactic" amiodarone therapy in patients with DCM in order to prevent sudden cardiac death. Despite growing evidence that implantable cardioverter defibrillator (ICD) therapy results in improved overall survival py preventing sudden cardiac death in patients at high risk for serious arrhythmic events, arrhythmia risk stratification with regard to prophylactic ICD implantation remains highly controversial in patients with DCM. CONCLUSION: This review describes potential arrhythmia mechanisms in DCM and summarizes the results of antiarrhythmic drug trials and of prophylactic ICD trials in patients with heart failure as well as our knowledge concerning arrhythmia risk stratification in patients with DCM.     

beta-Blockers in hypertension-the emperor has no clothes: an open letter to present and prospective drafters of new guidelines for the treatment of hypertension

Over the past decade, national and international guidelines have proposed beta-blockers to be used on an equal footing with diuretics for initial therapy of hypertension. This preferred status was supposedly based on evidence documenting a reduction in morbidity and mortality with beta-blocker therapy in hypertension. We systematically analyzed all available outcome studies and found no evidence that beta-blocker based therapy, despite lowering blood pressure, reduced the risk of heart attacks or strokes. Despite the inefficacy of beta-blockers, the incidence of adverse effects is substantial. In the MRC study, for every heart attack or stroke prevented, three patients withdrew from atenolol because of impotence, and another seven withdrew because of fatigue. Thus the risk/benefit ratio of beta-blockers is characterized by lack of efficacy and multiple adverse effects. Given that many thorough, prospective, randomized trials attest to efficacy and safety of diuretics, calcium antagonists, ACE inhibitors, and angiotensin receptor inhibitors, the time has come to admit that beta-blockers should no longer be considered appropriate for first-line therapy in uncomplicated hypertension.     

Beta-Adrenergic Blocking Drugs in the Treatment of Hypertension

The reduction in blood pressure seen with the use of beta-blocking drugs was an unexpected finding. Initially there was resistance to their use as the reduction of cardiac output and increase in peripheral resistance from beta-blockade was considered an undesirable pharmacological action for a drug in the treatment of hypertension. However, beta-blockers have now become established in the treatment of hypertension and have been recommended as a first line choice in various guidelines, although their exact mode of action remains a matter for debate. In broad terms beta-blocking drugs are at least of similar efficacy to the other major classes of antihypertensive drugs. They may be usefully combined with other anti-hypertensives, as is often required. There is some evidence that the beta- 1 selective agents are more efficacious than the non-selective beta-blockers. Notwithstanding some observations to the contrary beta-blockers are often effective antihypertensive agents in the elderly and in black patients; the combination of being elderly and black, however, appears to result in a reduced fall in blood pressure. If they are given early in pregnancy they lead to a low birth weight. Co-existant disease may influence the choice of a beta-blocker to treat hypertension. Beta-blockers are valuable agents in ischaemic heart disease, notably the control of chronic angina pectoris and to improve prognosis post-myocardial infarction. While initial dose titration has to be extremely careful, heart failure is now a strong indication for the use of a beta-blocker, as prognosis is much improved. Diabetes should no longer be regarded as a contra-indication to the use of a beta- 1 selective agent. Recent work confirms that beta-blockers should be given to patients undergoing surgery who have a high cardiac risk. Outcome studies suggest overall that in younger patients beta-blockers reduce the incidence of strokes and myocardial infarction. There is no convincing evidence of a difference between the ACE inhibitor captopril and the combination of diuretic and a beta-blocker. In high risk patients, i.e. those with diabetes, no difference was seen between captopril and atenolol. Diuretics may result in better outcome measurements in the elderly compared to beta-blockade but in combination, "conventional treatment" is as effective in terms of total mortality, strokes and myocardial infarction as ACE inhibitors or calcium antagonists. Co-existant asthma remains an important contra-indication to beta-blockade, but not chronic obstructive airways disease where a beta-blocker should be used with caution if it is indicated, e.g. post-infarction. Quality of life measurements, at least with beta- 1 selective agents compare favourably with other anti-hypertensive drugs. Beta-blockers, without partial agonist activity, should not be stopped abruptly, particularly in patients with, or at high risk of, co-existant ischaemic disease because of the danger of post-beta-blockade cardiac sympathetic hypersensitivity; alternatively bed rest should be instituted to reduce the risk of sympathetic stimulation.     

Beta-adrenergic blocking drugs in the treatment of hypertension

The reduction in blood pressure seen with the use of beta-blocking drugs was an unexpected finding. Initially there was resistance to their use as the reduction of cardiac output and increase in peripheral resistance from beta-blockade was considered an undesirable pharmacological action for a drug in the treatment of hypertension. However, beta-blockers have now become established in the treatment of hypertension and have been recommended as a first line choice in various guidelines, although their exact mode of action remains a matter for debate. In broad terms beta-blocking drugs are at least of similar efficacy to the other major classes of antihypertensive drugs. They may be usefully combined with other anti-hypertensives, as is often required. There is some evidence that the beta-1 selective agents are more efficacious than the non-selective beta-blockers. Notwithstanding some observations to the contrary beta-blockers are often effective antihypertensive agents in the elderly and in black patients; the combination of being elderly and black, however, appears to result in a reduced fall in blood pressure. If they are given early in pregnancy they lead to a low birth weight. Co-existant disease may influence the choice of a beta-blocker to treat hypertension. Beta-blockers are valuable agents in ischaemic heart disease, notably the control of chronic angina pectoris and to improve prognosis post-myocardial infarction. While initial dose titration has to be extremely careful, heart failure is now a strong indication for the use of a beta-blocker, as prognosis is much improved. Diabetes should no longer be regarded as a contra-indication to the use of a beta-1 selective agent. Recent work confirms that beta-blockers should be given to patients undergoing surgery who have a high cardiac risk. Outcome studies suggest overall that in younger patients beta-blockers reduce the incidence of strokes and myocardial infarction. There is no convincing evidence of a difference between the ACE inhibitor captopril and the combination of diuretic and a beta-blocker. In high risk patients, i.e. those with diabetes, no difference was seen between captopril and atenolol. Diuretics may result in better outcome measurements in the elderly compared to beta-blockade but in combination, "conventional treatment" is as effective in terms of total mortality, strokes and myocardial infarction as ACE inhibitors or calcium antagonists. Co-existant asthma remains an important contraindication to beta-blockade, but not chronic obstructive airways disease where a beta-blocker should be used with caution if it is indicated, e.g. post-infarction. Quality of life measurements, at least with beta-1 selective agents compare favourably with other anti-hypertensive drugs. Beta-blockers, without partial agonist activity, should not be stopped abruptly, particularly in patients with, or at high risk of, co-existant ischaemic disease because of the danger of post-beta-blockade cardiac sympathetic hypersensitivity; alternatively bed rest should be instituted to reduce the risk of sympathetic stimulation.     

Antihypertensive drug therapy in Saskatchewan: patterns of use and determinants in hypertension

BACKGROUND: The benefits of continuous treatment of hypertension have been extensively documented in randomized controlled trials. However, clinical trials may not reflect actual drug use in the population. OBJECTIVE: To examine the distribution and determinants of patterns of use of antihypertensive agents in the first 5 years of hypertension treatment in Saskatchewan. METHODS: Patterns of use and modifications to therapy were derived from a careful examination of medication use in a cohort of 19 501 subjects aged 40 to 79 years, without recognized cardiac disease and initiating therapy with an angiotensin-converting enzyme inhibitor, a calcium antagonist, or a beta-blocker in Saskatchewan between 1990 and 1993. RESULTS: Angiotensin-converting enzyme inhibitors (37.4%), followed by calcium antagonists (27.5%) and beta-blockers (26.4%), were the most commonly prescribed agents to initiate treatment in our study population. Patients with diabetes were less likely to be dispensed a beta-blocker, as were younger and female patients. Previous visits to a cardiologist decreased the likelihood of receiving combination therapy or angiotensin-converting enzyme inhibitors but increased that of using calcium antagonists. Apart from dose adjustment, 89% of study subjects underwent at least 1 modification to their initial regimen, at a median time of 134 days. After 1 year, only 33.8% of patients were still using their initial drug. An early decrease in the proportion of patients continuing to receive initial therapy was noted, especially among beta-blocker users. CONCLUSIONS: Erratic drug-taking behaviors were observed in this Saskatchewan population. In addition, initial drug use does not seem to be in accordance with the stepped-care approach to hypertension therapy recommended in the Canadian guidelines.     

Beta Blockers as Anti-Arrhythmic Agents

Although beta-adrenergic blocking agents are not always considered anti-arrhythmic drugs, the results of several recent trials have suggested an anti-arrhythmic mechanism for at least part of their mortality benefit in the treatment of chronic congestive heart failure. We review background experimental and clinical evidence for the anti-arrhythmic actions of beta-blockers and then review the results of published beta-blocker heart failure trials. A majority of trials showed improvement in overall survival as well as reduction in sudden death and ventricular arrhythmias with beta-blocker treatment. Although different effects were seen with different specific agents, these trials overall support a clinically significant anti-arrhythmic effect of several beta-blockers.     

Angiotensin type-1 receptor blockers in heart failure

Chronic heart failure is a common condition with a poor prognosis, usually associated with poor exercise tolerance and debilitating symptoms despite optimal modern therapy. Standard therapy includes diuretics, digoxin, angiotensin-converting enzyme inhibitors (ACEIs) and beta-blockers. Despite this, many patients remain symptomatic, and interest is high as to whether the angiotensin receptor blockers (ARBs) would offer further advantage to a patient already receiving quadruple therapy. In addition, some patients are intolerant of ACEIs, and for this group the ARBs seem a logical choice. This article reviews the evidence for the use of ARBs as a class in heart failure concentrating on clinical recommendations and clinical needs and evidence rather than purely on statistical issues of significance in trials. The trials to date have demonstrated clearly similar hemodynamic effects to those seen with ACEIs and variety of ancillary benefits such as improvements in endothelial function, anti-thrombotic effects, and effects on neurohormonal inhibition. There is consistent evidence of a preservation of exercise tolerance when patients with heart failure are crossed over from stable ACEI therapy, and when added to ACEIs exercise tolerance appears to increase with ARBs. In terms of major outcomes, the two largest trials, Elite-II and Val-Heft, demonstrate that angiotensin receptor blockers probably have a clinical role in improving mortality and morbidity as an alternative to ACEIs in those patients unable to tolerate these agents, which remain, however, the first choice in unselected patients with heart failure. There is a worrying suggestion of a negative interaction when ARBs are added to beta-blockers, which is a reason for caution in using the ARBs, not a reason not to use beta-blockers.