Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Beta blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are evidence-based medications for chronic heart failure, but little is known about the persistent use and clinical effectiveness of these medications. We evaluated the longer-term use of beta blockers and ACEIs/ARBs in patients with left ventricular systolic dysfunction and coronary artery disease. Patients with an ejection fraction <40% and coronary artery disease who had a cardiac catheterization from April 1994 through December 2005 were identified. Long-term patterns of beta-blocker and ACEI/ARB use were categorized as persistent, new, previous, or no use based on information from routine follow-up surveys. Characteristics among medication-use groups were explored, and survival associated with persistent use was determined. Of 3,187 patients identified for the beta-blocker analysis, 1,339 (42.0%) had persistent use. Conditional on surviving for > or = 2 follow-up surveys, the adjusted risk of death was statistically significantly lower with persistent use versus no use (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.65 to 0.82) and new use versus no use (HR 0.81, 95% CI 0.68 to 0.97). Adjusted risk of death was not statistically significantly different between persistent or new use of an evidence-based beta blocker and persistent use of a nonevidence-based beta blocker (HR 0.96, 95% CI 0.78 to 1.17). Of 3,166 patients identified for the ACEI/ARB analysis, 1,347 (42.5%) had persistent use. There was no statistically significant association between adjusted mortality and persistent use (HR 0.93, 95% CI 0.81 to 1.05), new use (HR 0.86, 95% CI 0.71 to 1.03), or previous use (HR 0.88, 95% CI 0.73 to 1.07) compared with no ACEI/ARB use. In conclusion, persistent and new use of beta blockers was associated with survival, but evidence-based beta blockers did not appear superior to nonevidence-based beta blockers. We were unable to demonstrate a statistically significant association between persistent ACEI/ARB use and survival.
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PMID:Association between mortality and persistent use of beta blockers and angiotensin-converting enzyme inhibitors in patients with left ventricular systolic dysfunction and coronary artery disease. 1946 9

The 2005 American Heart Association/American College of Cardiology heart failure (HF) guidelines contributed to a renewed focus on "at-risk" patients and emphasized HF as a progressive disease. Patient categorization by stages focused attention on customization of therapy to achieve optimal, evidence-based treatments across the HF continuum. Therapy for risk factors that predispose patients to left ventricular dysfunction or other symptoms may help reduce HF development. beta-Blockers are valuable for treatment of HF; however, the class is heterogeneous, and proper beta-blocker selection for each HF stage is important. beta-Blockers have been used routinely to treat patients with stage A HF with hypertension. Recent controversy regarding the detrimental effects that some beta-blockers have on metabolic parameters has raised inappropriate concerns about the use of any beta-blocker for diabetes. beta-Blockade is standard therapy for the patient with stage B HF who has had a myocardial infarction, but few data are available concerning use in asymptomatic patients with left ventricular dysfunction. Additionally, beta-blockers are part of the core therapy for stage C HF and selected patients with stage D HF. This review examines the role and use of beta-blockers in each HF stage through an evidence-based approach to provide better understanding of their importance in this progressive disease. PubMed searches (1980-2008) identified large clinical trials that evaluated cardiovascular events and outcomes in any HF stage or hypertension. Search terms were heart failure, hypertension, beta-blocker, ACEI, ARB, and calcium channel blocker AND blood pressure coronary artery disease, diabetes, efficacy, left ventricular dysfunction, metabolism, mortality, myocardial infarction, or stroke.
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PMID:Beta-blocker use for the stages of heart failure. 1964 89

The renin-angiotensin-aldosterone system (RAAS), an important regulator of blood pressure as well as fluid and electrolyte balance, plays an important role in the pathophysiology of cardiovascular and kidney diseases. Blockade of the RAAS with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-II (ANG-II) receptor blockers (ARBs) lowers blood pressure, decreases morbidity and mortality in patients with chronic heart failure, and decreases proteinuria and the rate of decline in renal function in patients with chronic kidney disease. Although these drugs are highly effective and are widely used in the management of cardiovascular and kidney diseases, current treatment regimens with ACEIs and ARBs may not completely suppress the RAAS. Combinations of ACEIs and ARBs have been shown to be superior to either agent alone for some, but certainly not all, composite cardiovascular and kidney outcomes. With the growing appreciation of the role of aldosterone in the pathogenesis of cardiorenal diseases and the recent approval of the direct renin inhibitor (DRI), aliskiren, additional combination strategies have emerged that may offer novel ways to more fully suppress the RAAS. This review examines what is presently known about ACEI/ARB combination therapy and explores alternative combination strategies that include DRIs and mineralocorticoid receptor blockers (MRBs).
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PMID:Dual blockade of the renin-angiotensin-aldosterone system: beyond the ACE inhibitor and angiotensin-II receptor blocker combination. 1966 25

Many of the quality measures for patients with heart failure (HF) or acute myocardial infarction (AMI) require the completion of comprehensive discharge instructions, including instructions about medications to be taken after discharge. To improve compliance in a tertiary care teaching hospital with these evidence-based quality measures, a clinical-decision-support system (CDSS) that uses an electronic checklist was developed. The CDSS prompts clinicians at every training level to consistently create comprehensive discharge instructions addressing quality measures. The authors compared compliance during the 15-month preintervention and postintervention periods. Compliance with discharge measures for AMI (i.e., aspirin, beta-blocker, angiotensin-converting enzyme inhibitor [ACEI], or angiotensin receptor blocker [ARB] use) and for HF (i.e., discharge instructions, left ventricular systolic function [LVSF] evaluation, and ACEI/ARB use) was assessed. The delivery of discharge instructions showed significant improvement from the preintervention period to the postintervention period (37.2% to 93.0%; P < .001). Compliance with prescription of ACEI or ARB also improved significantly for HF (80.7% to 96.4%; P < .001) and AMI (88.1% to 100%; P = .014) patients. Compliance with the remaining measures was higher before intervention, and, thus, the modest improvement in the postintervention period was not statistically significant (AMI patients: aspirin, 97.5% to 98.8%; P = .43; and beta-blocker, 97.9% to 98.7%; P = .78; HF patients: LVSF, 99.3% to 99.1%; P = .78). Implementation of a CDSS with computerized electronic prompts improved compliance with selected cardiac-care quality measures. The design of quality-improvement decision-support tools should incorporate educational missions in their message and design.
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PMID:Effectiveness of a clinical-decision-support system in improving compliance with cardiac-care quality measures and supporting resident training. 1994 May 79

The HOPE and EUROPA clinical studies have shown that treatment with the angiotensin-converting enzyme (ACE) inhibitors, ramipril and perindopril, may reduce the occurrence of major cardiovascular events in patients with proven atherosclerotic disease. The recently published results of the PRoFESS and TRANSCEND trials completed the much needed information concerning the use of an angiotensin receptor blocker for patients at high risk of cardiovascular events. PROFESS compared a therapy of telmisartan 80 mg daily with placebo in patients with a recent ischemic stroke. The difference in the primary outcome of first recurrent stroke was not statistically significant between telmisartan and placebo. The secondary outcome of major cardiovascular events showed a relative risk reduction (RRR) of 7% in favour of telmisartan. This tended to be significant (p = 0.06) despite a rather short follow-up period of only 28 months. In TRANSCEND 5926 patients at high risk for cardiovascular events were randomized to a treatment with telmisartan 80 mg daily or placebo for a mean duration of follow-up of 56 months. The primary composite outcome of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure showed a non-significant 8% RRR in favour of the telmisartan treated patients. The main secondary outcome of cardiovascular death and myocardial infarction or stroke as used in the HOPE trial showed a non-significant RRR of 13% in favour of telmisartan treated patients (p = 0.068 adjusted for multiplicity of comparisons). In comparing the Kaplan-Meier curves for the endpoint of major cardiovascular events used in HOPE, EUROPA, TRANSCEND and PRoFESS, the trends are similar. Results of most of the recently published trials have been neutral.This could partly be explained by major improvements in the optimal background therapy of the patients included. Nevertheless, the results of PRoFESS and TRANSCEND do not contradict the results from previous studies with theACE inhibitors ramipril and perindopril and the ARB telmisartan.
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PMID:Are ACE-inhibitors or ARB's still needed for cardiovascular prevention in high risk patients? Insights from profess and transcend. 2049 60

The cardiovascular and cardiorenal disease continuum comprises the transition from cardiovascular risk factors to endothelial dysfunction and atherosclerosis, to clinical complications such as myocardial infarction (MI) and stroke, to the development of persistent target-organ damage and, ultimately, to chronic congestive heart failure (CHF), end-stage renal disease or premature death. The renin-angiotensin-aldosterone system (RAAS) is involved in all steps along this pathway, and RAAS blockade with ACE inhibitors or angiotensin AT(1)-receptor antagonists (angiotensin receptor blockers; ARBs) has turned out to be beneficial for patient outcomes throughout the disease continuum. Both ACE inhibitors and ARBs can prevent or reverse endothelial dysfunction and atherosclerosis, thereby reducing the risk of cardiovascular events. These drugs have further been shown to reduce end-organ damage in the heart, kidneys and brain. Aldosterone antagonists such as spironolactone and eplerenone are increasingly recognized as a third class of RAAS inhibitor with potent risk-reducing properties, especially but not solely with respect to the inhibition of cardiac remodelling and the possible prevention of heart failure. In secondary prevention, head-to-head comparisons of ACE inhibitors and ARBs, such as the recent ONTARGET study, provided evidence that, in addition to better tolerability, ARBs are non-inferior to ACE inhibitors in the prevention of clinical endpoints such as MI and stroke in cardiovascular high-risk patients. However, the combination of both ramipril and telmisartan at the maximally tolerated dosage achieved no further benefits and was associated with more adverse events such as symptomatic hypotension and renal dysfunction. In acute MI complicated by heart failure, the VALIANT trial has shown similar effects of ACE inhibition with captopril and ARB treatment with valsartan, but dual RAAS blockade did not further reduce events. In CHF, meta-analyses of RESOLVD, ValHeFT and CHARM-ADDED have shown that combined RAAS inhibition with an ACE inhibitor and ARB significantly reduced the morbidity endpoint in certain patient subgroups compared with standard therapy. However, in clinical practice, dual RAAS blockade is rarely employed, as seen, for instance, in the CORONA trial. The RALES and EPHESUS trials, investigating the effects of aldosterone blockade on cardiovascular outcomes in CHF patients, revealed that the addition of an aldosterone antagonist to standard heart failure therapy conferred powerful relative risk reductions for both morbidity and mortality. Future studies will elucidate whether this also holds true for patients who are asymptomatic or who have heart failure with preserved ejection fraction. In selected patients with renal disease, several studies have suggested that combined RAAS blockade brings about additional renoprotective antiproteinuric effects independent of blood pressure reduction, and large trials with robust endpoints are underway. In summary, combined therapy with several RAAS inhibitors is not recommended for all patients along the cardiorenovascular continuum. Patients with CHF with incomplete neuroendocrine blockade, as indicated, for example, by repetitive cardiac decompensation or refractory symptoms, might benefit from dual therapy as long as safety issues are well controlled. Finally, novel pharmacological agents such as the direct renin inhibitor aliskiren may provide additional therapeutic tools, but their role has yet to be established.
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PMID:Optimal antagonism of the Renin-Angiotensin-aldosterone system: do we need dual or triple therapy? 2056 30

Diabetic cardiomyopathy is a type of cardiac dysfunction resulting from diabetes, independent of vascular or valvular pathology. It clinically manifests initially as asymptomatic diastolic dysfunction and then progresses to symptomatic heart failure. Two major contributors to the development of diabetic cardiomyopathy, which are unique to diabetes, are hyperglycemia and diabetes-related alterations in myocardial metabolism. Diabetes mellitus is characterized by reduced glucose and lactate metabolism and enhanced fatty acid metabolism, which are the early consequences of the disease. Studies on the effect of intensive glucose control on heart failure events in patients with diabetes have been conducted with neutral results. However, no study on the effect of metabolic modulators on the prevention of heart failure has been reported. Trimetazidine, a 3-ketoacyl coenzyme A thiolase (3-KAT) inhibitor, shifts cardiac energy metabolism from free fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-KAT, and is used clinically as an effective antianginal agent. Studies have shown that trimetazidine improves heart function in patients with idiopathic cardiomyopathy and in diabetic patients with cardiac ischemia or heart failure. In addition to being effective, trimetazidine has only mild side effects. Therefore, instead of routine administration of trimetazidine for the treatment of diabetic cardiomyopathy, we hypothesize that the early application of trimetazidine may prevent or ameliorate diabetic cardiomyopathy. In addition to life style modifications, ACEI, ARB, and beta-blockers, which have been recommended in the past, trimetazidine should be administered to those patients with impaired glucose tolerance or patients in the early course of diabetes. In this way, we may reduce the prevalence of heart failure and improve the long-term survival of patients with diabetes through early normalization of the myocardial substrate metabolism.
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PMID:Early administration of trimetazidine may prevent or ameliorate diabetic cardiomyopathy. 2093 48

Medical management of systolic heart failure is standardized and based on international guidelines. They promote the use of combination therapy based on neurohormonal blockade targeting both the renin-angiotensin system (with ACE inhibitors or ARB) and sympathetic nervous system (i.e., beta blockers). Drugs have to be titrated at the maximum tolerated level. In symptomatic patients, loop diuretics remain the treatment of choice with dosage adaptation according to symptoms and fluid management. Aldosterone antagonists are indicated in patients with severe heart failure (i.e., NYHA class 3 or 4) and creatinine clearance above 30 ml/min. Their combination with RAS blockers warrants strict biological follow up.
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PMID:[Medical management of chronic systolic heart failure]. 2103 91

Brain inflammation has a critical role in the pathophysiology of brain diseases of high prevalence and economic impact, such as major depression, schizophrenia, post-traumatic stress disorder, Parkinson's and Alzheimer's disease, and traumatic brain injury. Our results demonstrate that systemic administration of the centrally acting angiotensin II AT(1) receptor blocker (ARB) candesartan to normotensive rats decreases the acute brain inflammatory response to administration of the bacterial endotoxin lipopolysaccharide (LPS), a model of brain inflammation. The broad anti-inflammatory effects of candesartan were seen across the entire inflammatory cascade, including decreased production and release to the circulation of centrally acting proinflammatory cytokines, repression of nuclear transcription factors activation in the brain, reduction of gene expression of brain proinflammatory cytokines, cytokine and prostanoid receptors, adhesion molecules, proinflammatory inducible enzymes, and reduced microglia activation. These effects are widespread, occurring not only in well-known brain target areas for circulating proinflammatory factors and LPS, that is, hypothalamic paraventricular nucleus and the subfornical organ, but also in the prefrontal cortex, hippocampus, and amygdala. Candesartan reduced the associated anorexic effects, and ameliorated associated body weight loss and anxiety. Direct anti-inflammatory effects of candesartan were also documented in cultured rat microglia, cerebellar granule cells, and cerebral microvascular endothelial cells. ARBs are widely used in the treatment of hypertension and stroke, and their anti-inflammatory effects contribute to reduce renal and cardiac failure. Our results indicate that these compounds may offer a novel and safe therapeutic approach for the treatment of brain disorders.
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PMID:Angiotensin II AT1 receptor blockade ameliorates brain inflammation. 2115 Sep 13

Observations available for patients with acute heart failure (HF) show conflicting results, and the prognostic role of anaemia ascertained on hospital admission is not well defined. We investigated the database of the Italian Survey on Acute Heart Failure (IS-AHF) to analyze prevalence, factors associated with and the prognostic role of anaemia (defined as haemoglobin < 12 g/dl) in patients hospitalized for acute HF with either depressed or preserved (>40%) ejection fraction (EF). The median haemoglobin level of the 2,318 patients considered in this analysis was 13 g/dl (inter-quartile range 11.5-14.3). The prevalence of anaemia was 31%. Patients who had anaemia were older, more frequently female gender, hospitalized for a chronic destabilized HF, had higher prevalence of preserved EF, hyponatremia, elevated troponin and other comorbidities (including diabetes, peripheral artery disease, chronic renal failure) than those who did not have anaemia. During the hospital stay, they were treated with higher doses of diuretics, and more frequently required mechanical ventilation and ultrafiltration, and less frequently received ACEi/ARB, aldosterone blockers and beta-blockers at hospital discharge. In-hospital mortality was 12.1 and 5.3% in patients with and without anaemia, respectively (p < 0.0001). In the multivariable analysis, anaemia was a significant independent predictor of in-hospital mortality apart from age, low systolic blood pressure, impaired renal function, elevated troponin assay, the non use of beta-blocker and the requirement of inotropic drug. In conclusion, anaemia diagnosed at hospital admission for acute HF is a frequent comorbidity with meaningful implications on the clinical management and prognosis both in patients with reduced and preserved EF.
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PMID:Prevalence and prognostic role of anaemia in patients with acute heart failure and preserved or depressed ventricular function. 2154 36


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