Recent clinical trials have explored whether angiotensin receptor blockers (ARBs) or aldosterone blockade should be added to standard angiotensin‐converting enzyme (ACE) inhibitor/β blocker treatment in heart failure. Both strategies are of some value but it is unclear which strategy should be used first in patients with mild but symptomatic heart failure. The arguments for and against each strategy are discussed. The strongest argument for aldosterone blockade is the consistency in the results of the RALES (Randomized Aldactone Evaluation Study) and EPHESUS (Eplerenone Post‐acute Myocardial Infarction Heart Failure Efficacy and Survival Study) studies, but what is lacking is a trial of aldosterone blockade in patients with mild, symptomatic heart failure as such. The strongest argument for ARBs is that the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) Added trial result was positive in the precise patient population of interest (mild, symptomatic heart failure). The strength of this argument is diminished by the somewhat different results in Val‐HeFT (Valsartan Heart Failure Trial). A third possibility is to use neither an ARB nor an aldosterone blocker and arguments can be marshalled for this position also. Clinicians should now assess these various arguments to select what they believe would be best for their patients.
In seeking to implement evidence based medicine for the patient with heart failure occurring after a myocardial infarction (MI), much can be learnt from the long road to delivery of best care for the patient with chronic heart failure (CHF) caused by left ventricular systolic dysfunction. Both patient groups are part of the same cardiovascular continuum. A mass of evidence has accrued for the beneficial effects of angiotensin converting enzyme inhibitors, ß blockers, and aldosterone antagonists on both morbidity and mortality across a wide spectrum of patient severity. This evidence has informed the development of management guidelines, although registry data showed that uptake of treatments remained low, leading to research focused on how heart failure care could be delivered more effectively. This has resulted in a range of heart failure management programmes, many of which have been shown to reduce hospital admission rates and to improve adherence with treatments. Multidisciplinary heart failure management programmes that span primary and secondary care are now considered a routine "standard" to be aspired to in delivering effective CHF care. Applying such an approach to the care of the post-MI heart failure patient should be equally important.
Patients with heart failure, left ventricular systolic dysfunction, or both, after acute myocardial infarction have a poor prognosis. It is important to focus treatment on this high risk group to reduce the persistently high morbidity and mortality after acute myocardial infarction. As in chronic heart failure, there is now good evidence that inhibition of the renin–angiotensin–aldosterone system and sympathetic nervous system, with the appropriate drugs, can reduce morbidity and mortality. In addition to angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and ß blockers, the aldosterone blocker eplerenone has now been shown to be effective in reducing adverse outcomes.
Heart failure is a common and disabling condition with morbidity and mortality that increase dramatically with advancing age. Large observational studies, retrospective subgroup analyses and meta-analyses of clinical trials in systolic heart failure, and recently published randomized studies have provided data supporting the use of beta-blockers as a baseline therapy in heart failure in the elderly. Despite the available evidence about beta-blockers, this therapy is still less frequently used in elderly compared to younger patients. Nebivolol is a third-generation cardioselective beta-blocker with L-arginine/nitric oxide-induced vasodilatory properties, approved in Europe and several other countries for the treatment of essential hypertension, and in Europe for the treatment of stable, mild, or moderate chronic heart failure, in addition to standard therapies in elderly patients aged 70 years old or older. The effects of nebivolol on left ventricular function in elderly patients with chronic heart failure (ENECA) and the study of effects of nebivolol intervention on outcomes and rehospitalization in seniors with heart failure (SENIORS) have been specifically aimed to assess the efficacy of beta-blockade in elderly heart failure patients. The results of these two trials demonstrate that nebivolol is well tolerated and effective in reducing mortality and morbidity in older patients, and that the beneficial clinical effect is present also in patients with mildly reduced ejection fraction. Moreover, nebivolol appears to be significantly cost-effective when prescribed in these patients. However, further targeted studies are needed to better define the efficacy as well as safety profile in frail and older patients with comorbid diseases.
beta-blockers; therapy; older; left ventricular dysfunction; prognosis
Chronic heart failure (HF) is a major cause of morbidity and mortality particularly in the elderly and a growing healthcare burden in Italy. The objective was to assess the cost-effectiveness of candesartan cilexetil, an angiotensin II type 1 receptor blocker (ARB) for the treatment of HF. A pre-specified economic evaluation was conducted on resource utilization (cardiovascular drug treatment, cardiovascular and non-cardiovascular hospital admission, cardiovascular procedures/operations) prospectively collected alongside the CHARM program, a series of parallel randomized clinical trials comparing candesartan with placebo (standard therapy) in patients with NYHA Class II-IV HF: CHARM-Alternative (LVEF ≤40% patients not receiving ACE inhibitors because of previous intolerance); CHARM-Added (LVEF ≤40% patients currently receiving ACE inhibitors); or CHARM-Preserved (LVEF ≥40% patients). The primary outcome for the component trials was the composite of cardiovascular death or worsening hospital admission for HF and of the overall program all-cause mortality. Adjunctive treatment with candesartan in CHARM-Alternative and CHARM-Added led to clinical benefits and to either cost-savings or a small additional cost, depending on the trial. The less certain clinical benefit in CHARM-Preserved was obtained at modest extra cost. The incremental cost-effectiveness ratios (ICERs) were estimated to range from €713 per life year gained for CHARM-Alternative to dominant for CHARM-Added and the pooled reduced LVEF trials.
candesartan; heart failure; cost-effectiveness analysis; cost-consequence analysis; CHARM; Italy
Hypertensive patients with diabetes exhibit an increased risk for cardiovascular complications, such as acute coronary syndrome, stroke, heart failure and chronic kidney disease (CKD). These two chronic diseases are linked to a high rate of morbidity and mortality and for this reason it is important for the clinician to recognize the need for effective treatment of hypertension, which can require combination therapy to achieve blood pressure (BP) goals. Direct renin inhibitors (DRIs) may be useful in combination with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) as they provide a more complete blockade of the renin–angiotensin–aldosterone system (RAAS), effectively suppressing residual angiotensin II production and the counter-regulatory increase in plasma renin activity observed in patients receiving monotherapy with ACEIs or ARBs. Some questions regarding the action of aliskiren in cardiovascular and renal disorders are open. In particular, the combination therapy of aliskiren and a RAAS blocker in diabetic hypertensive patients with CKD is controversial. Several published studies demonstrated that aliskiren is suitable for once-daily administration and its antihypertensive effect is comparable or superior to that of other antihypertensive agents at recommended doses, with a good tolerability profile. At the moment the association with ACEIs and ARBs is not recommended in patients with type 2 diabetes mellitus (T2DM) and renal impairment even if a recent published open-label study of low-dose aliskiren (150 mg/daily) in association with ACEIs or ARBs has demonstrated a good tolerability profile without the adverse events found in other studies. This review provides a brief overview of RAAS blocking, in particular the rationale and clinical evidence supporting the use of the DRI aliskiren, in high-risk patients with T2DM.
aliskiren; diabetes; diabetic nephropathy; hypertension; RAAS; renin
The prevalence of heart failure is ever increasing around the world, particularly due to aging populations. Despite improvements in treatment over the last 20 years, the prognosis for heart failure remains poor. Among the treatments recommended for chronic heart failure, angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are crucial, provided of course that they are not contraindicated. However, angiotensin II receptor blockers (ARBs) can also be a beneficial treatment option. Candesartan is a particular ARB, characterized by a strong binding affinity to the angiotensin II type 1 receptor and slow dissociation. The benefits of candesartan have been demonstrated by the CHARM programme, which showed that candesartan significantly reduces the incidence of cardiovascular death, hospital admissions for decompensated heart failure, and all-cause mortality in chronic heart failure patients with altered left ventricular systolic function, when added to standard therapies or as an alternative to ACE inhibitors when these are poorly tolerated. Furthermore, candesartan can protect against myocardial infarction, atrial fibrillation and diabetes. Tolerance to candesartan is good, but blood pressure and serum potassium and creatinine levels must be monitored.
chronic heart failure; angiotensin II receptor blockers; candesartan; left ventricular systolic function
Survivors of myocardial infarction (MI) are at high risk of disability and death. This is due to infarct-related complications such as heart failure, cardiac remodeling with progressive ventricular dilation, dysfunction, and hypertrophy, and arrhythmias including ventricular and atrial fibrillation. Angiotensin (Ang) II, the major effector molecule of the renin–angiotensin–aldosterone system (RAAS) is a major contributor to these complications. RAAS inhibition, with angiotensin-converting enzyme (ACE) inhibitors were first shown to reduce mortality and morbidity after MI. Subsequently, angiotensin receptor blockers (ARBs), that produce more complete blockade of the effects of Ang II at the Ang II type 1 (AT1) receptor, were introduced and the ARB valsartan was shown to be as effective as an ACE inhibitor in reducing mortality and morbidity in high-risk post-MI suvivors with left ventricular (LV) systolic dysfunction and and/or heart failure and in heart failure patients, respectively, in two major trials (VALIANT and Val-HeFT). Both these trials used an ACE inhibitor as comparator on top of background therapy. Evidence favoring the use of valsartan for secondary prevention in post-MI survivors is reviewed.
valsartan; myocardial infarction; infarct survivors; remodeling; heart failure
Ischaemic heart disease and congestive heart failure are common and important conditions in family practice. Effective treatments may be underutilized, particularly in women and the elderly. The objective of the study was to determine the rate of prescribing of evidence-based cardiovascular medications and determine if these differed by patient age or sex.
We conducted a two-year cross-sectional study involving all hospitals in the province of Nova Scotia, Canada. Subjects were all patients admitted with ischaemic heart disease with or without congestive heart failure between 15 October 1997 and 14 October 1999. The main measure was the previous outpatient use of recommended medications. Chi-square analyses followed by multivariate logistic regression analyses were used to examine age-sex differences.
Usage of recommended medications varied from approximately 60% for beta-blockers and angiotensin converting enzyme (ACE) inhibitors to 90% for antihypertensive agents. Patients aged 75 and over were significantly less likely than younger patients to be taking any of the medication classes. Following adjustment for age, there were no significant differences in medication use by sex except among women aged 75 and older who were more likely to be taking beta-blockers than men in the same age group.
The use of evidence-based cardiovascular medications is rising and perhaps approaching reasonable levels for some drug classes. Family physicians should ensure that all eligible patients (prior myocardial infarction, congestive failure) are offered beta-blockers or ACE inhibitors.
The advantages of blood pressure (BP) control on the risks of heart failure and stroke are well established. The renin-angiotensin system plays an important role in volume homeostasis and BP regulation and is a target for several groups of antihypertensive drugs. Angiotensin II receptor blockers represent a major class of antihypertensive compounds. Candesartan cilexetil is an angiotensin II type 1 (AT) receptor antagonist (angiotensin receptor blocker [ARB]) that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system. Oral candesartan 8–32 mg once daily is recommended for the treatment of adult patients with hypertension. Clinical trials have demonstrated that candesartan cilexetil is an effective agent in reducing the risk of cardiovascular mortality, stroke, heart failure, arterial stiffness, renal failure, retinopathy, and migraine in different populations of adult patients including patients with coexisting type 2 diabetes, metabolic syndrome, or kidney impairment. Clinical evidence confirmed that candesartan cilexetil provides better antihypertensive efficacy than losartan and is at least as effective as telmisartan and valsartan. Candesartan cilexetil, one of the current market leaders in BP treatment, is a highly selective compound with high potency, a long duration of action, and a tolerability profile similar to placebo. The most important and recent data from clinical trials regarding candesartan cilexetil will be reviewed in this article.
angiotensin receptor blockers; candesartan; candesartan cilexetil; clinical trials; efficacy studies; safety; blood pressure
Treatment with specific beta-blockers reduces mortality and hospitalisation in heart failure.
To describe trends and inequities in beta-blocker prescribing for heart failure.
Design of study
Repeated cross-sectional analysis of a nationally representative primary care database (DIN-LINK).
A total of 152 UK general practices.
Prescribing of beta-blockers between 2000 and 2005 was examined among a yearly average of 7294 patients aged ≥50 years who had actively managed heart failure — defined as a recorded diagnosis of heart failure and two prescriptions of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker during the calendar year. The main outcome was the prescription of a guideline-recommended beta-blocker (bisoprolol, carvedilol, metoprolol, or nebivolol) in the year. Determinants of beta-blocker prescribing were analysed using logistic regression.
Between 2000 and 2005, age-adjusted use of recommended beta-blockers rose from 6.1% to 27.0% in men, and from 4.2% to 21.5% in women. In 2005, younger patients were more likely to be treated; the fully adjusted odds ratio was 4.83 (95% confidence interval = 3.78 to 6.17) for patients aged 60–64 years compared with those aged 85 years. Women and patients living in areas of socioeconomic deprivation were less likely to be treated. In 2005, in addition to treatment with guideline-recommended beta-blockers, a further 11.7% of men and 12.5% of women were prescribed other beta-blockers.
Recommended beta-blocker use has risen in the UK but remains low and inequitable, with many patients still treated with beta-blockers that are not recommended in guidelines. This suggests further improvements in prescribing are still possible.
adrenergic; beta-blockers; equity; heart failure
Risk of morbidity and mortality in patients with severe heart failure (HF) is reduced by blockade of aldosterone receptors with spironolactone. However, benefits of spironolactone are potentially limited by treatment compliance and adverse events profile. The aim of this study was to estimate use of spironolactone by patients with HF, incidence of key adverse events, and patient compliance.
This study was performed using data from the Quebec provincial medical and drug plans (Régie de l'Assurance Maladie du Québec, RAMQ) for patients who had a diagnosis of HF. Relative incidence of gynecomastia and hyperkalemia was estimated for users and non-users of spironolactone. Treatment adherence was estimated for users of spironolactone and compared to adherence with angiotensin converting enzyme (ACE) inhibitors, beta-blockers (β-blockers), and angiotensin receptor blockers (ARBs).
RAMQ data were obtained for a total of 82,018 patients with a diagnosis of HF. Of these patients, 59.9% used an ACE inhibitor, 59.5% used a beta-blocker, 28.4% used an ARB, and 15.1% (n = 12,344) used spironolactone. Despite underestimation due to limitation of the database, the documented incidence of hyperkalemia (3.3% versus 1.4%) and gynecomastia (1.8% versus 0.7%) was significantly higher in spironolactone users than non-users (p < 0.001). Treatment compliance was significantly lower with spironolactone compared to ACE inhibitors, β-blockers, and ARBs (45.6% versus 56.1%, 59.7%, and 57.0%, respectively; p < 0.001). Persistence to treatment over a one-year period was also lower with spironolactone compared to ACE inhibitors, β-blockers, and ARBs (50.7% versus 64.5%, 70.4%, and 66.3%, respectively; p < 0.001).
Use of spironolactone is associated with an incidence of adverse events, which may have an impact on treatment compliance.
Most information about the use of guideline-recommended therapies for heart failure reflects what occurred at discharge after an inpatient stay.
Using a nationally representative, community-dwelling sample of elderly Medicare beneficiaries, we examined how the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), and beta-blockers has changed and factors associated with their use.
Using data from the Medicare Current Beneficiary Survey cost and use files matched with Medicare claims data, we identified beneficiaries for whom a diagnosis of heart failure was reported between January 1, 2000, and December 31, 2004. Data on medications prescribed during the year of cohort entry were based on patient self-report. We used multivariable logistic regression to explore relationships between the use of ACE inhibitors/ARBs and beta-blockers and patient demographic characteristics.
From 2000 through 2004, the use of ARBs increased from 12% to 19%, and the use of beta-blockers increased from 30% to 41%. The use of ACE inhibitors remained constant at 45%. Beneficiaries who reported having prescription drug insurance coverage were 32% more likely than other beneficiaries to have filled a prescription for an ACE inhibitor or ARB and 26% more likely to have filled a prescription for a beta-blocker.
Although the use of guideline-recommended therapies for heart failure has increased, it remains suboptimal.
Evidence-Based Practice; Guidelines as Topic; Heart Failure; Medicare
Clinical outcomes of patients with chronic heart failure (CHF) have improved, but evidence-based treatment appears to be imbalanced depending on patients' and physicians' gender. We aimed to determine the interactions of gender with medical treatment of CHF.
Methods and results
Consecutive patients with CHF (n = 1857) were evaluated regarding co-morbidities, New York Heart Association classification, current medical treatment, and dosage of angiotensin-converting enzyme-inhibitors (ACE-Is) and beta-blockers. Gender of patients and treating physicians was recorded. Baseline characteristics of patients and physicians were comparable for males and females. Female patients were less frequently treated with ACE-Is, angiotensin-receptor blockers, or beta-blockers. Achieved doses were lower in female compared with male patients. Guideline-recommended drug use and achieved target doses tended to be higher in patients treated by female physicians. There was no different treatment for male or female patients by female physicians, whereas male physicians used significantly less medication and lower doses in female patients. In multivariable analysis, female gender of physicians was an independent predictor of use of beta-blockers.
Treatment of CHF is influenced by patients', but also physicians' gender with regard to evidenced-based drugs and their dosage. Physicians should be aware of this problem in order to avoid gender-related treatment imbalances.
Gender; Chronic heart failure; ACE inhibitor; Angiotensin antagonist
Specific blockers of the angiotensin type1 receptor, angiotensin receptor blockers (ARBs), have been introduced as an alternative to angiotensin-converting enzyme inhibitors (ACEi) for the treatment of heart failure. In comparison with ACEi, ARBs are better tolerated and have similar effects on haemodynamics, neurohormones and exercise capacity. Early studies have suggested that ARBs might have a superior effect on mortality. However, the first outcome trial, ELITE II (Losartan Heart Failure Survival Study), did not show any significant difference between losartan and captopril in terms of mortality or morbidity. This commentary outlines the role of ARBs in the treatment of heart failure.
angiotensin-converting enzyme inhibitor; angiotensin receptor blocker; efficacy; heart failure; tolerability
Heart failure is common and is associated with poor prognosis. Chronic kidney disease is common in heart failure, and shares many risk factors with heart failure such as age, hypertension, diabetes, and coronary artery disease. Over half of all heart failure patients may have moderate to severe chronic kidney disease. The presence of chronic kidney disease is associated with increased morbidity and mortality, yet it is also associated with underutilization of evidence-based heart failure therapy that may reduce morbidity and mortality. Understanding the epidemiology and outcomes of chronic kidney disease in heart failure is essential to ensure proper management of these patients.
Heart failure; chronic kidney disease; epidemiology; risk factors; management
We sought to examine associations between initiation of beta-blocker therapy and outcomes among elderly patients hospitalized for heart failure.
Beta-blockers are guideline-recommended therapy for heart failure, but their clinical effectiveness is not well-understood, especially in elderly patients.
We merged Medicare claims data with OPTIMIZE-HF records to examine long-term outcomes of eligible patients newly initiated on beta-blocker therapy. We used inverse probability-weighted Cox proportional hazards models to determine the relationships between treatment and mortality, rehospitalization, and a combined mortality–rehospitalization endpoint.
Observed 1-year mortality was 33%, and all-cause rehospitalization was 64%. Among 7154 patients hospitalized with heart failure and eligible for beta-blockers, 3421 (49%) were newly initiated on beta-blocker therapy. Among patients with left ventricular systolic dysfunction (LVSD; n = 3001), beta-blockers were associated with adjusted hazard ratios of 0.77 (95% confidence interval [CI], 0.68–0.87) for mortality, 0.89 (95% CI, 0.80–0.99) for rehospitalization, and 0.87 (95% CI, 0.79–0.96) for mortality–rehospitalization. Among patients with preserved systolic function (n = 4153), beta-blockers were associated with adjusted hazard ratios of 0.94 (95% CI, 0.84–1.07) for mortality, 0.98 (95% CI, 0.90–1.06) for rehospitalization, and 0.98 (95% CI, 0.91–1.06) for mortality-rehospitalization.
In elderly patients hospitalized with heart failure and LVSD, incident beta-blocker use was clinically effective and independently associated with lower risks of death and rehospitalization. Patients with preserved systolic function had poor outcomes, and beta-blockers did not significantly influence the mortality and rehospitalization risks for these patients.
Adrenergic beta-Antagonists; Heart Failure; Mortality; Patient Readmission
Cardiovascular disease (CVD) is the leading cause of death in patients with serious mental illness (SMI) and in patients with Type 2 diabetes. Inadequate pharmacologic care for CVD may partially explain poor health outcomes in individuals with both conditions. We sought to identify patients in this group at greatest risk for suboptimal pharmacologic management.
Among individuals with Type 2 diabetes and SMI identified from Maryland Medicaid data, we evaluated patient and service utilization factors associated with the prescription of HMG-CoA reductase inhibitors (“statins”) for hyperlipidemia and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for chronic kidney disease, congestive heart failure, and hypertension.
From 2001 to 2003, the annual prevalence of use of statins and ACE-inhibitors/ARBs ranged from 44–59%, with rates increasing each year. Being female, having certain cardiovascular conditions, and having a greater number of outpatient visits for diabetes increased the odds of receiving statins and ACE-inhibitors/ARBs. More frequent contact with the mental health system was associated with a lower likelihood of receipt of both medication classes; having a substance use disorder was associated with reduced use of statins. African-Americans were less likely than Caucasians to receive statins, but more likely to receive prescriptions for ACE-inhibitors/ARBs.
Although use of cardioprotective medications in individuals with Type 2 diabetes and SMI increased over the study period, a considerable proportion of patients remained inadequately managed despite their considerable cardiac risk. Further study should focus on observed racial variations and strategies to increase the capacity of mental health contacts to improve prescribing of these agents.
Diabetes; serious mental illness; Medicaid database analysis
Heart failure is a frequent complication after acute myocardial infarction (MI) and carries a poor prognosis. Current treatments inhibit the renin-angiotensin-aldosterone system but suppression of aldosterone may be incomplete. The aldosterone antagonist spironolactone has been shown to improve survival in patients with chronic, severe heart failure. Eplerenone is a selective aldosterone antagonist expected to have a lower incidence of hormonal side effects than spironolactone.
To assess the evidence on the therapeutic value of eplerenone for treatment of heart failure in adults.
The evidence base consists of one large double-blind placebo-controlled multicenter randomized trial in over 6000 patients with postmyocardial infarction (MI) heart failure, comparing eplerenone plus standard therapy with placebo plus standard therapy. All the main outcomes were patient-oriented. Evidence from this trial shows that eplerenone improves survival and reduces cardiovascular hospitalization/mortality, compared with standard treatment alone. The incidence of hormonal side effects is no greater than with placebo. The risk of hyperkalemia is significantly increased, especially in patients with low creatinine clearance. Eplerenone was both more effective and more costly than standard treatment alone. The cost-effectiveness ratio has been estimated at $US10 402–21 876 per life-year gained.
Place in therapy:
Eplerenone reduces mortality compared with current treatment alone in patients with post-MI heart failure, at additional cost. Direct comparative evidence is needed to assess its efficacy versus spironolactone. It may be valuable in patients who are intolerant to the hormonal side effects of spironolactone.
eplerenone; evidence; heart failure; left ventricular dysfunction; myocardial infarction; survival
Clinical practice guidelines have been slowly and inconsistently applied in clinical practice, and certain evidence-based, guideline-driven therapies for heart failure (HF) have been significantly underused. The purpose of this study was to survey guideline compliance and its effect on clinical outcomes in the treatment of systolic HF in Korea.
Method and Results
The SUrvey of Guideline Adherence for Treatment of Systolic Heart Failure in Real World (SUGAR) trial was a multi-center, retrospective, observational study on subjects with systolic HF (ejection fraction <45%) admitted to 23 university hospitals. The guideline adherence indicator (GAI) was defined as a performance measure on the basis of 3 pharmacological classes: angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor II blocker (ARB), beta-blocker (BB), and aldosterone antagonist (AA). Based on the overall adherence percentage, subjects were divided into 2 groups: those with good guideline adherence (GAI ≥50%) and poor guideline adherence (GAI <50%). We included 1319 regional participants as representatives of the standard population from the Korean national census in 2008. Adherence to drugs at discharge was as follows: ACEI or ARB, 89.7%; BB, 69.2%; and AA, 65.9%. Overall, 82.7% of the patients had good guideline adherence. Overall mortality and re-hospitalization rates at 1 year were 6.2% and 37.4%, respectively. Survival analysis by log-rank test showed a significant difference in event-free survival rate of mortality (94.7% vs. 89.8%, p = 0.003) and re-hospitalization (62.3% vs. 56.4%, p = 0.041) between the good and poor guideline-adherence groups.
Among patients with systolic HF in Korea, adherence to pharmacologic treatment guidelines as determined by performance measures, including prescription of ACEI/ARB and BB at discharge, was associated with improved clinical outcomes.
Secondary analyses of clinical trial data suggest that, compared with other agents, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) are associated with lower risk of incident atrial fibrillation (AF) in patients with heart failure, but data from the hypertension trials have been inconsistent. Information is scant about the association of beta-blocker use with AF risk in hypertensive patients without heart failure.
We conducted a population-based case-control study to determine whether antihypertensive treatment with ACE inhibitors/ARBs or beta-blockers, compared with diuretics, was associated with the risk of incident AF in a community practice setting. All patients (810 AF cases, 1,512 control subjects) were members of Group Health, an integrated health-care delivery system, were pharmacologically treated for hypertension, and did not have heart failure. Medical records were reviewed to confirm the diagnosis of incident AF and to collect information on medical conditions and health behaviors. Information on antihypertensive medications was obtained from a pharmacy database.
Single-drug users of an ACE inhibitor/ARB had a lower risk of incident AF compared with single-drug users of a diuretic (adjusted odds ratio [OR] 0.63, 95% confidence interval [CI] 0.44–0.91). Single-drug use of beta-blockers was not significantly associated with lower AF risk (OR 1.05, 95% CI 0.73–1.52), and none of the most commonly-used two-drug regimens was significantly associated with AF risk, compared with single-drug use of diuretic.
In a general hypertensive population without heart failure, single-drug use of ACE inhibitors/ARBs was associated with lower AF risk.
Chronic heart failure is a common clinical syndrome that may have different causes. Its incidence and prevalence are predicted to rise substantially over the next 10 years. There are therefore major consequences for resource provision, especially in primary care, where most patients are managed. Chronic heart failure is a serious condition with high morbidity and mortality. There is good evidence to show that treatment with angiotensin-converting enzyme (ACE) inhibitors in patients with left ventricular systolic dysfunction improves symptoms and signs, slows progression of heart failure, reduces hospitalisation rates, and improves survival. Despite this evidence, primary care studies show that patients with heart failure are incorrectly diagnosed and inadequately treated. Most patients present in general practice, and because effective treatment relies on a correct diagnosis, this is a key step in the appropriate management of heart failure. The aim of this paper is to review the evidence about the usefulness of signs, symptoms, and investigations in diagnosing heart failure in primary care. To identify relevant studies for this review, four strategies were used: a MEDLINE search from 1993 to January 1998 using the diagnosis search filter; a MEDLINE search from 1993 to January 1998 using the guideline search filter to locate published heart failure guidelines; a search for review articles in the Cochrane Library; and a check of references in the studies identified. The search terms included MeSH terms and the keywords 'heart failure' and 'diagnosis'. All searches were limited to humans and English language articles. Studies were included in this review on the basis of quality and relevance to primary care. The review shows that symptoms and signs are important because they alert clinicians to the possibility of heart failure as a diagnosis. However, they are not sufficiently specific for confirming left ventricular systolic dysfunction. From the evidence available, a patient with suspected heart failure must have objective tests to confirm the diagnosis. These should include an electrocardiogram and, ideally, an echocardiogram. Further research is also needed on the usefulness of signs and symptoms in primary care, as most studies of heart failure have been conducted in secondary care.
Previous studies have demonstrated that women hospitalized for heart failure receive poorer quality of care and have worse outcomes than men. However, these studies were based upon selected patient populations and lacked quality of care measures.
We used data from the National Heart Failure Project, a national sample of fee-for-service Medicare patients hospitalized with heart failure in the United States in 1998–1999, to evaluate differences in quality of care and patient outcomes between men and women. Multivariable hierarchical logistic regression models and χ2 analyses were used to examine sex differences in the documentation of left ventricular systolic function (LVSF), prescription of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for patients with left ventricular dysfunction, and mortality within 30 days and 1 year of admission in the study cohort (n = 30 996).
Women had lower overall rates of LVSF assessment than men (64.9% vs 69.5%, P < .001). Among patients classified as candidates for ACE inhibitor prescription, women had lower crude rates of ACE inhibitor prescription than men (70.1% vs 74.2%, P = .015), but treatment rates were similar when evaluating the prescription of ACE inhibitors or ARBs (78.9% women vs 81.3% men, P = .11). Despite lower rates of treatment, women had lower mortality rates than men at 30 days (9.2% vs 11.4%, P < .001) and 1 year (36.2% vs 43.0%, P < .001) after admission. Results were similar after multivariable adjustment.
There were small sex differences in the quality of care provided to fee-for-service Medicare patients hospitalized with heart failure, although women had higher rates of survival than men up to 1 year after hospitalization.
About 5 million Americans suffer from heart failure. Given the correlation of heart failure with age and the rising life expectancy, the prevalence of heart failure continues to increase in the general population. Sympathetic stimulation intensifies with progressive heart failure. The rationale to use β-blockers in individuals with impaired myocardial function is based on experimental evidence supporting the notion that prolonged α- and β-adrenergic stimulation leads to worsening heart failure. Until recently, safety concerns have precluded the use of β-blockers in patients with diabetes and heart failure. However, several large, randomized, placebo-controlled clinical trials such as Metoprolol Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) have shown that β-blockers can be safely used in patients with diabetes and heart failure. Moreover, β-blockers significantly improved morbidity and mortality in this population. Based on this evidence, it is now recommended to add β-blockers such as metoprolol CR/XL with an escalating dosage regimen to the treatment of patients with symptomatic heart failure who already are receiving a stable medical regimen including angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, diuretics, vasodilators, or digitalis.
metoprolol; heart failure; diabetes mellitus; β-adrenergic blocking agents; MERIT-HF
Heart Failure (HF) accounted for 3.4 mill ambulatory visits in 2000. Current guidelines from the American Heart Association (AHA) and the American College of Cardiology (ACC), the Heart Failure Society of America (HSFA), and the International Society for Heart & Lung Transplantation (ISHLT) recommend aggressive pharmacologic interventions for patients with HF. This may include a combination of diuretics, angiotensin-converting enzyme (ACE) inhibitors, β-blockers, angiotensin-receptor blockers (ARBs), aldosterone antagonists, and digoxin. Nitrates and hydralazine are also indicated as part of standard therapy in addition to β-blockers and ACE inhibitors, especially but not exclusively, for African Americans with left ventricular (LV) systolic dysfunction. For those with acute decompensated HF, additional treatment options include recombinant human B-type natriuretic peptide, and in the future possible newer agents not yet approved for use in the United States, such as Levosimendan. Medical devices for use in patients with advanced HF include LV assist devices, cardiac resynchronization therapy, and implantable cardioverter defibrillators. For refractory patients heart transplantation, the gold-standard surgical intervention for the treatment of refractory HF, may be considered. Newer surgical options such as surgical ventricular restoration may be considered in select patients.
heart failure; cardiac transplantation; cardiomyopathy; myocarditis