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

The cost of caring for a growing number of patients with congestive heart failure is a staggering economic burden. Fortunately, an increasing number of evidence-based guidelines have been developed which, if implemented, have the potential to save lives and money. In addition, there are newer understandings about the potential of current therapies, both medical and surgical, to prevent the progression of disease. The foundation of diuretics, ACE inhibitors and beta-blockers serves to improve symptoms, decrease hospitalizations and improve survival. The roles of angiotensin receptor antagonists and cytokine antagonists are currently being clarified. The potential for myocardial recovery during left ventricular assist implantation has paved the way for some exciting surgical procedures. The challenge in the future will be to develop an approach to the patient with heart failure which takes advantage of this new knowledge while avoiding a bewildering array of costly drugs which may not all be necessary at all stages of the disease.
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PMID:New approaches in the management of patients with chronic congestive heart failure. 1297 76

To determine whether angiotensin receptor blockade decreases vascular tone in heart failure by improving endothelial-dependent vasorelaxation and increasing nitric oxide (NO) bioavailability, we treated infarcted adult male Sprague-Dawley rats with candesartan for 7 days or 8 weeks (10 mg/kg/day in drinking water). Candesartan, at both time points, lowered left ventricular (LV) systolic pressure (P < 0.05) (122 +/- 22 versus 74 +/- 16 and 73 +/- 10 mm Hg) and LV dP/dt (5914 +/- 1294 versus 2857 +/- 1672 versus 3175 +/- 769 mm Hg/s), but lowered LV end-diastolic pressure only at 8 weeks (16.9 +/- 9.7 versus 11.2 +/- 5.7 versus 6.9 +/- 5.3 mm Hg). The vasorelaxation response to acetylcholine (ACh) in thoracic aortic segments was decreased with infarction (P < 0.05), remained unchanged with 1 week of candesartan, but increased 84 and 86% at 10-4 and 10-5 M ACh (P < 0.05) at 8 weeks. The enhanced candesartan-induced vasorelaxation at 8 weeks was abolished with NG-nitro-l-arginine methyl ester (200 microM). In bovine pulmonary endothelial cells, 20 microM candesartan increased endothelial nitric-oxide synthase (eNOS) protein levels (P < 0.05) (28.9 +/- 2.6 versus 16.1 +/- 3.7 intensity units/microg of protein); the increased eNOS was abolished by a specific angiotensin subtype 2 (AT2) receptor antagonist, PD 123319. These data suggest that AT1 receptor blockade enhances vasorelaxation in heart failure by increasing NO bioavailability, in part via an AT2 receptor-mediated up-regulation of eNOS protein.
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PMID:Angiotensin subtype 1 rReceptor (AT1) blockade improves vasorelaxation in heart failure by up-regulation of endothelial nitric-oxide synthase via activation of the AT2 receptor. 1456 36

Recent evidence from randomized controlled trials has provided compelling evidence to support the use of beta blockers in most patients with heart failure due to systolic dysfunction. There is little disagreement about the mortality benefit provided by adding beta blockers to standard therapy, which may include angiotensin-converting enzyme inhibitors, diuretics, and sometimes digoxin. A few areas are still controversial. The authors review the available literature encompassing four of those controversial areas: 1) the comparability among beta blockers; 2) the utility of beta blockers among patients with New York Heart Association class I and class IV heart failure symptoms; 3) the impact of race on the effectiveness of beta blockers; and 4) the safety and efficacy of beta blockers among patients on concomitant therapy with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or spironolactone.
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PMID:Controversies in the use of beta blockers in heart failure. 1456 43

The renin-angiotensin-aldosterone system contributes to the progression of heart failure and its inhibition slows ventricular remodelling and favourably affects morbidity and mortality. beta-blockers exert a remarkably favourable effect on progression that may be mediated at least in part by renin inhibition. Although earlier trials suggested a possible adverse interaction when an angiotensin receptor blocker was added to an angiotensin-converting enzyme inhibitor and a beta-blocker, a recent study and newly analysed mechanistic data indicate that the triple combination provides modest additional inhibition of angiotensin that can further slow progression of disease.
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PMID:Interaction of beta-blockers and angiotensin receptor blockers/ACE inhibitors in heart failure. 1460 16

Collectively, a series of large, prospective randomised outcome trials has now shown that angiotensin receptor blockers (ARBs) are of clinical value in a broad spectrum of patients with symptomatic heart failure, regardless of background therapy and ventricular function. There is a clear benefit of ARBs in patients unable to tolerate an angiotensin- converting enzyme (ACE) inhibitor and this benefit is of a similar magnitude to that obtained with an ACE inhibitor (ACE-I). Both Val-HeFT and, particularly, CHARM-Added, also show that symptoms, morbidity and mortality are further reduced if an ARB is added to an ACE-I. This benefit is not only statistically significant but clinically important. CHARM-Preserved showed that candesartan can reduce hospital admission for heart failure in patients with preserved systolic function though more definitive outcome data are needed in this group.
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PMID:Angiotensin receptor blockers in heart failure. 1460 22

The antihypertensive drug classes that have reduced cardiovascular events safely either in large placebo-controlled trials or in comparison with other effective antihypertensive drugs in large morbidity trials are diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs). Although control of blood pressure (BP) is a primary goal of therapy, evidence from several clinical trials suggests that certain antihypertensive agents provide clinical benefits independent of their effect on BP. In the recently reported Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), an ACE inhibitor, a CCB, and an alpha-blocker reduced coronary events and mortality to a similar extent as a thiazide-type diuretic, but the diuretic reduced one or more major cardiovascular events, especially heart failure, more than the other agents. In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial, the ARB losartan reduced cardiovascular morbidity (primarily stroke) more than the beta-blocker atenolol. Although an ARB has not yet been compared with a diuretic in a morbidity trial, as most patients require more than one drug to control BP, and a diuretic plus an ARB is a very effective and well-tolerated combination, this uncertainty applies to a minority of patients. A primary goal in treating hypertension should be to reach a patient's goal BP, but initial selection of drugs based on hypertension morbidity study results and other compelling indications should be given priority.
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PMID:Are there benefits to specific antihypertensive drug therapy? 1462 58

Hypertension is the most common reason Americans visit a physician. Recent analyses from the Framingham Heart Study and others have shown that there will be 70 million hypertensive Americans by the year 2020 and that the overwhelming majority of hypertensives will be 65 years of age or older (what we used to call elderly). The lifetime risk of Americans who live to age 85 years of becoming hypertensive is approximately 90% for both men and women. These individuals, even if they develop an elevated blood pressure late in life, are at significantly increased risk of the many medical complications attributable to hypertension (coronary artery disease, strokes, heart failure, chronic renal disease, and more). Older hypertensives are more likely to have an elevated systolic blood pressure and a low diastolic blood pressure, both of which are related to a loss of article compliance and have an increase in left ventricular mass and a decrease in peripheral resistance. We now have a substantial body of evidence from well done clinical trials that older hypertensives benefit as much or more than younger patients from antihypertensive therapy, so there is no longer any justification for withholding medication from any hypertensive patient whose competing risk or other medical problems are not a contraindication to treatment. These same studies, and practice-based analyses, have shown that the major barrier to reaching blood pressure goal is our failure to reduce systolic blood pressure to <140 mm Hg in most patients and to <130 mm Hg in diabetics and those with renal failure. The basis for all antihypertensive therapy, especially in older people, is thiazide diuretics with either angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, or calcium entry blockers as appropriate add-on treatment. The choice of the second agent depends on other factors, such as comorbidity, lifestyle, and affordability. We must be more aggressive in getting the message out that older hypertensives benefit from treatment and we must overcome the clinical inertia that seems to be a factor in the decision of many physicians not to treat an older patient. No older person should suffer a preventable, life-threatening event or become confined to a wheel chair if attention to lifestyle issues and a few pills a day could avoid that outcome.
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PMID:Management of older hypertensive patients: is there a difference in approach? 1468 89

The use of angiotensin-receptor blockers has already been outlined in cardiology and diabetology. In extending clinical indications of this drug class their pleiotropic actions might play a role: they are improving endothelial function, and their antiatherogenic effect is not related to antihypertensive action. It may also be important that while some antihypertensive agents are impairing sexual function, angiotensin-receptor blocking agents seem to improve sexual activity in hypertensive men. As there is alternative route for angiotensin II synthesis, there are patients in whom blockade of angiotensin II actions do need more aggressive treatment for proper therapeutic results. The discovery of angiotensin-receptor blocking agents made possible to produce this blockade in the tissues as well, and suggested combined administration of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for better clinical results. In patients with congestive heart failure data from an earlier pilot study (RESOLVD) suggested that combined use of these two drug classes would lead for a more complete blockade of the renin-angiotensin system with better clinical results, especially in those patients in the higher dose ranges. Recent results showed that using this drug combination cardiovascular mortality and hospitalization because of worsening heart failure could significantly be decreased (CHARM-Added study). More important data are expected from the ongoing ONTARGET program (Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial).
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PMID:[New possibilities in clinical use of angiotensin II receptor inhibitors]. 1472 9

Chronic heart failure (CHF) is a common disease with high associated morbidity and mortality, and the outcome appears to be worse in black compared with white patients. There is currently no clear consensus for basing the pharmacological treatment of CHF on racial differences. Most studies that have investigated the potential effects of racial differences on pharmacological responses in heart failure have been based on African Americans and white participants. Using these data, this review will discuss the current understanding of the effects of racial differences in response to pharmacotherapy in heart failure, possible mechanisms for these observed differences, and how this may impact on patient management. Diuretics have favorable symptomatic benefits in both black and white patients with heart failure with evidence of fluid retention. ACE inhibitors seem to be less effective in the treatment of black patients with heart failure compared with white patients. This may be due to low pre-existing activity of the renin-angiotensin system in blacks. The role of angiotensin receptor blockers (ARBs) in the management of all patients with heart failure is incompletely defined and there are no clear trial data to show any difference in effect between black and white patients with heart failure. There is good evidence for the use of spironolactone in all patients with heart failure, but no evidence for a different effect in black patients. Similarly, there is no conclusive data to suggest a difference in effect of digoxin in different racial groups. The evidence available would suggest that certain beta-adrenoceptor antagonists (certainly carvedilol but not bucindolol) are effective in both black and white patients with CHF. The combination of hydralazine and nitrates would appear to be particularly effective in black patients with CHF though the African American Heart Failure Trial (A-HeFT) trial should provide clearer evidence for the potentially greater beneficial effects of these two drugs in the black population. It is important to accept that racial categorization acts as only a surrogate marker for genetic or other factors responsible for individual responses to drug therapy and that any identified differences will not apply to all members of each stratified group. Nonetheless, in managing a complex, common and often fatal condition such as heart failure, recognizing potential individual differences in drug responses should enable the responsible clinician to provide a tailored and evidence-based approach to patient treatment.
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PMID:Racial differences in responses to drug treatment: implications for pharmacotherapy of heart failure. 1472 54

The renin-angiotensin system (RAS) is well recognized for its importance in regulation of BP, electrolyte balance and vascular growth. Pharmacological suppression of the RAS, through ACE inhibition and/or angiotensin receptor blockade, is a proven effective therapeutic approach to the treatment of a range of cardiovascular diseases. Renin is the enzyme that catalyzes the first and rate-limiting step of RAS, the cleavage of angiotensinogen to angiotensin I (A-I). A-I is then further converted by ACE to the biologically active vasoconstrictor, A-II. Interruption of the generation of A-II by renin inhibitors at this highly specific initial step of the cascade would be expected to have similar but not identical effects to those of the already well established RAS antagonists. Due to the lack of effective alternative enzyme pathways, blockade of A-II production may be more effective with renin inhibition than with ACE inhibition, and because of the high specificity of renin for only one substrate, namely angiotensinogen, adverse effects would be expected to be less frequent. It is currently unclear whether blockade of angiotensin II type 1 receptors (AT(1)), leaving other A-II receptors unblocked, is preferable to the reduction in plasma and tissue A-II levels achieved with either ACE or renin inhibition. The development of early peptidic and peptidomimetic renin inhibitors was hampered by problems with oral bioavailability and high costs of synthesis. However recent work has led to the synthesis of a potent non-peptidic inhibitor of renin, aliskiren, which has acceptable oral bioavailability. This renin inhibitor has been shown to effectively reduce A-II levels in normal volunteers and to lower BP in patients with mild to moderate hypertension. It appears likely that aliskiren is the first of a new class of agents that may prove useful in the management of patients with nephropathy, heart failure and atherosclerosis in addition to hypertension.
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PMID:Therapeutic potential of renin inhibitors in the management of cardiovascular disorders. 1472 59


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