UMLS:C0018801 - FACTA Search

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Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this article, 2 leading physicians debate the strength of outcome data on the efficacy of angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs) for reducing the incidence of cardiovascular, cerebrovascular, and renovascular events. Dr. Stephen G. Ball notes that the efficacy of ACE inhibitors for reducing the risk for myocardial infarction independent of their effects on blood pressure is controversial. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril treatment in high-risk patients was associated with a 20% reduction in the risk for myocardial infarction; mean reduction in blood pressure was 3 mm Hg for systolic blood pressure and 1 mm Hg for diastolic blood pressure. The HOPE investigators propose that the 20% reduction was much greater than would be expected based on the observed blood pressure reduction. However, a meta-regression analysis of blood pressure reduction in >20 antihypertensive therapy outcome trials found that the reduction in myocardial infarction risk with ramipril observed in HOPE was consistent with the modest blood pressure reduction seen with that agent. Nevertheless, there are convincing data for prevention of myocardial infarction with ACE inhibitors in patients with heart failure, including those with heart failure after myocardial infarction, as well as supportive evidence from studies in patients with diabetes mellitus and concomitant hypertension. On the other hand, Dr. William B. White takes the position that ARBs are well-tolerated antihypertensive agents that specifically antagonize the angiotensin II type 1 (AT(1)) receptor and provide a more complete block of the pathologic effects of angiotensin II-which are mediated via the AT(1) receptor-than ACE inhibitors. The Evaluation of Losartan in the Elderly (ELITE) II study and the Valsartan Heart Failure Trial (ValHeFT) suggest that ARBs reduce the risk for mortality in patients with congestive heart failure. The Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension trial also demonstrated beneficial effects of ARBs in the prevention of stroke events. The Irbesartan in Patients with Diabetes and Microalbuminuria (IRMA) study, the Irbesartan Diabetic Nephropathy Trial (IDNT), and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated significant reductions in the rate of progression of renal disease in patients receiving ARBs, independent of effects on blood pressure. These data support the use of ARBs, in addition to the standard of care, in hypertensive patients with heart failure who are intolerant of ACE inhibitors, and also provide compelling evidence for their use in patients with hypertension and type 2 diabetes.
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PMID:Debate: angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers--a gap in evidence-based medicine. 1451 6

The renin-angiotensin system evolved to maintain volume homeostasis and blood pressure and to prevent ischemia during acute volume loss. But in the present age, these mechanisms are redundant, and the clinical significance of angiotensin II results from its pathologic effects, which are mediated by the angiotensin II type 1 (AT(1)) receptor. Activation of AT(1) receptors has been linked to pathologic processes that contribute to atherosclerosis and ischemic events, including oxidative stress, inflammatory processes, low-density lipoprotein cholesterol trafficking, and prothrombotic states. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) program will compare the efficacy of the angiotensin II receptor blocker (ARB) telmisartan, the angiotensin-converting enzyme (ACE) inhibitor ramipril, and combination therapy with telmisartan plus ramipril for reducing cardiovascular risk. The ARB telmisartan is distinguished by its long duration of action, which compares favorably with some other ARBs and conventional antihypertensives. Ramipril was shown in the Heart Outcomes Prevention Evaluation (HOPE) study to reduce the risk for myocardial infarction (MI) and other cardiovascular events in patients at high risk for cardiovascular events but without heart failure or a low ejection fraction. The ONTARGET program consists of 2 randomized, double-blind, multicenter international trials: a principal trial, ONTARGET, and a parallel trial, Telmisartan Randomized Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease (TRANSCEND). The treatment arms for the principal ONTARGET study are telmisartan 80 mg, ramipril 10 mg, and combination therapy with telmisartan 80 mg plus ramipril 10 mg; for the parallel study TRANSCEND, the treatment arms are telmisartan 80 mg and placebo. Both trials will assess cardiovascular outcomes in patients at high risk using the same criteria as that of the HOPE study, with a single exception: the TRANSCEND trial will enroll patients who do not tolerate ACE inhibitor treatment. The primary end points in both ONTARGET and TRANSCEND are death caused by cardiovascular disease, acute MI, stroke, and hospitalization because of congestive heart failure. The secondary end points include newly diagnosed heart failure, revascularization, new-onset type 2 diabetes mellitus, nephropathy, cognitive decrease and dementia, and newly diagnosed atrial fibrillation; these will be used for hypothesis generation.
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PMID:The ongoing telmisartan alone and in combination with ramipril global endpoint trial program. 1278 6

Blood pressure reduction and intensive antihypertensive treatment are effective in reducing both microvascular and macrovascular complications in type 2 diabetes. Blood pressure target levels < 130/85 or 130/80 mmHg are now recommended. Antagonism of the renin-angiotensin-aldosterone system seems to be an important goal in the treatment of hypertension and diabetes-related complications. The renoprotective role of angiotensin-converting enzyme (ACE)-inhibitors has been well documented in type 1 diabetes; in type 2 diabetes ACE-inhibitors have been deemed more effective than other traditional drugs in reducing the onset of overt nephropathy in microalbuminuric patients (secondary prevention) but not in reducing renal dysfunction in patients with clinical proteinuria (tertiary prevention). Recently, four large trials performed on type 2 diabetes showed that angiotensin II receptor blockers (ARBs) prevent the development of clinical proteinuria in microalbuminuric patients (IRMA and MARVAL studies) and delay the progression of nephropathy towards end-stage renal failure in patients with overt nephropathy (IDNT and RENAAL studies). Moreover, ARBs have been deemed more effective in reducing hospitalizations for heart failure compared to placebo (IDNT and RENAAL studies) and in reducing cardiovascular morbidity and mortality compared to conventional therapy (LIFE study) in type 2 diabetes. In conclusion, ARBs are effective in preventing and delaying renal damage in type 2 diabetes. Thus, the recent guidelines for the prevention and treatment of diabetic nephropathy state that ACE-inhibitors are the first-choice drugs in type 1 diabetes while ARBs are considered as the first-choice drugs in secondary prevention, the same as ACE-inhibitors, and are the unique first-choice drug in tertiary prevention of end-stage renal failure in type 2 diabetes. Finally, ACE-inhibitors and ARBs are both first-choice drugs in cardiovascular prevention in type 2 diabetes.
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PMID:[The role of angiotensin II AT1-receptor antagonists in renal and cardiac protection in type-2 diabetes mellitus]. 1278 55

The ability of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) to lower blood pressure (BP) is well established. ACE inhibitors (ACE-Is) have also been shown to improve the prognosis of a broad range of patients at high cardiovascular risk, including those with heart failure, post-myocardial infarction (MI), and nephropathy. These benefits suggest that interrupting the renin-angiotensin-aldosterone system (RAAS) with ACE-Is has a widespread vasculoprotective effect, provided that BP is also adequately controlled. Evidence that RAAS blockade by ARBs also improves long-term clinical outcomes in patients with cardiovascular disease has started to accumulate, and will be tested further during the coming years as a number of large-scale, prospective trials are completed. These trials are investigating the long-term protective effects of ARBs on morbidity and mortality in patients with hypertension, heart failure, diabetes mellitus, acute MI, or established vascular disease. The results should establish the extent to which ARBs exhibit the vasculoprotective properties demonstrated by ACE-Is in patients at high cardiovascular risk. If ARBs are found to provide benefits that are similar to, or even greater than ACE-Is, it may have important implications for drug selection, given the excellent tolerability of ARBs. Some studies are also investigating whether more extensive RAAS blockade using a combination of an ARB and an ACE-I will offer even greater protection than either agent alone.
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PMID:Angiotensin II receptor blockers and cardiovascular outcomes: what does the future hold? 1280 87

The blockade of the renin-angiotensin system in the heart failure using ACE inhibitors, based on numerous clinical studies, demonstrated significant decrease in morbidity and mortality in the patients. Discovery of angiotensin II receptor antagonists brought about a new possibility of blockade of the rennin-angiotensin system. The blockade of the renin-angiotensin system with angiotensin II receptor antagonists should have been more effective and comprehensive than that induced by ACE inhibitors. However, the first studies with angiotensin II receptor antagonists in heart failure did not confirm that the antagonists are superior in reducing mortality and hospitalization in patients with heart failure when compared with ACE inhibitors. For the time being, the ACE inhibitors remain the current therapy of choice in treating heart failure. Angiotensin II receptor antagonists are a reasonable alternative in patients who cannot be treated with ACE inhibitors because of adverse effects. Clinical studies currently under way with angiotensin II receptor antagonists may alter these conclusions.
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PMID:[Angiotensin II antagonists in the treatment of cardiac decompensation]. 1282 85

Recent studies suggest that changes in the periphery, like those occurring in the skeletal muscles of patients with chronic heart failure, might play an important role in the origin of symptoms and exercise intolerance in this condition. Biochemical and histologic changes in the skeletal muscles of chronic heart failure patients relate with the degree of exercise intolerance better than hemodynamics parameters. A reduction in skeletal muscle mass represents another important determinant of exercise intolerance in chronic heart failure patients. The relationship between skeletal muscle changes and exercise intolerance suggests the possibility of modifying the peripheral changes in order to improve functional capacity in chronic heart failure patients. Recent studies have shown that the administration of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers can improve the properties of the skeletal muscles. Similarly, exercise training allows improvement in peak oxygen consumption, which parallels important biochemical and histologic changes in the skeletal muscles.
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PMID:Skeletal muscle abnormalities in chronic heart failure patients: relation to exercise capacity and therapeutic implications. 1282 73

There are now a number of guidelines outlining the diagnosis and management of patients with chronic heart failure (CHF). The extent to which these guidelines are used and the effects on patient outcomes are not well known. The aim of this study was to examine the implementation of a heart failure guideline among cardiologist and non-cardiologist physicians in a university hospital setting. Case record data were examined from 400 patients with a primary diagnosis of CHF. Management of these patients was assessed using a systolic heart failure guideline (Scottish Intercollegiate Guideline Network, number 35) as a benchmark. Hospital admission data were examined contemporaneously over a 17-month period to assess associations between adherence to drug therapies and number of admissions. Overall, there was poor adherence to the guideline, with relatively high use of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) (80%), low use of beta-blockers (32%) and digoxin (36%), and very low use of spironolactone (13%). Cardiologists used more beta-blockers (37 vs. 21%, P=0.003) and digoxin in sinus rhythm (18 vs. 5%, P<0.001) than non-cardiologists. Hospital admission rate was individually associated with increasing age, NYHA status, beta-blocker, diuretic and spironolactone prescription (all P<0.001). At multivariable analysis, only age, NYHA status and increased diuretic prescription were associated with more frequent admission (P<0.001, R(2)=0.15). Despite carefully designed guidelines, the implementation of evidence-based therapies for CHF remains inadequate, even in a university hospital environment. This may reflect a lack of organisational developments to facilitate the increasingly complex management of patients with CHF.
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PMID:Management of chronic heart failure due to systolic left ventricular dysfunction by cardiologist and non-cardiologist physicians. 1292 18

The renin-angiotensin system is activated during myocardial ischemia, and angiotensin II is locally formed in ischemic hearts. At least four angiotensin II receptor subtypes have been identified, the AT1- and the AT2-receptor being the most prominent in the cardiovascular system. AT1-receptor blockade--like inhibition of the angiotensin-converting-enzyme (ACE)--limits infarct size, improves functional recovery following myocardial ischemia and attenuates ventricular remodeling, post-myocardial infarction and the resulting development of heart failure. The potential mechanisms responsible for the cardioprotection by AT1-receptor blockade remain to be elucidated in detail, but appear to involve AT2-receptor activation and--like ACE-inhibitors--bradykinin and prostaglandins. Combined treatment with ACE-inhibitors and AT1-receptor blockers has the potential to further reduce infarct size and improve ventricular remodeling over each monotherapy alone.
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PMID:AT1-receptor blockade in experimental myocardial ischemia/reperfusion. 1294 May 36

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are recognized primarily for their use in hypertension, in heart failure, and after myocardial infarction. New evidence, particularly with ACE inhibitors, has shown their ability to reduce acute coronary events associated with atherosclerosis in patients without a history of the aforementioned cardiac conditions. This is likely due to inhibitory effects on the renin-angiotensin system--a system that adversely influences fibrinolytic balance, vascular endothelial function, and vascular inflammation, all key components of atherosclerotic progression and adverse coronary outcomes. Results of various studies suggest favorable effects of ACE inhibitors and ARBs on markers of these components, including effects on plasminogen activator inhibitor-1, endothelin-1, and nitric oxide by ACE inhibitors, and effects on vascular cell adhesion molecule-1 and C-reactive protein by ARBs. Although early evidence suggests that ACE inhibitors may provide a greater beneficial effect on some of these markers compared with ARBs, and that certain ACE inhibitors may provide greater vascular benefits than others, further investigation is required to verify such findings. Overall, understanding the distinct coronary vascular benefits of these agents will emphasize the importance of using them, particularly ACE inhibitors, to improve outcomes in patients with coronary atherosclerotic disease.
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PMID:Pharmacologic blockade of the renin-angiotensin system: vascular benefits beyond commonly understood pharmacologic actions. 1452 46

A 54-year-old man with diabetes mellitus, peripheral vascular disease, and hypertension was admitted to the hospital for an acute exacerbation of chronic heart failure. Therapy with intravenous furosemide and oral losartan 100 mg twice/day was begun. Ten days later, the patient's blood urea nitrogen and serum creatinine levels rose and peaked at 110 and 6.0 mg/dl, respectively. His serum potassium level increased to 5.7 mg/dl, urine output dropped to 400 ml over 24 hours, and mental status changes occurred. Magnetic resonance angiography revealed bilateral renal artery stenosis. After losartan was discontinued and hemodialysis was performed for 3 consecutive days, the patient's renal function returned to his baseline level. Reports in the medical literature reinforce the importance of recognizing that angiotensin-converting enzyme inhibitors should be used with caution in patients with bilateral renal artery stenosis. However, the literature is not as definitive about using of angiotensin II receptor blockers (ARBs) in these patients. Our patient's experience suggests that ARBs should be used with caution in patients with bilateral renal artery stenosis. Clinicians should be aware that renal failure might occur when using ARBs in these patients.
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PMID:Acute renal failure secondary to angiotensin II receptor blockade in a patient with bilateral renal artery stenosis. 1516 10

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