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

Angiotensin II receptor blockers (ARBs) are the most recent class of anti-hypertensive drug to enter clinical use for chronic heart failure (CHF). In the landmark Valsartan Heart Failure Trial (Val-HeFT), valsartan reduced the risk of the combined endpoint of all-cause mortality and morbidity by 13.2% over a 2-year follow-up. Although it significantly improved a pre-specified primary endpoint, it did not improve the endpoint of all-cause mortality. Valsartan administered to patients not receiving angiotensin-converting enzyme inhibitors (ACEI) at baseline reduced the endpoint of all-cause mortality by 33% and the combined endpoint of mortality and morbidity by 44%, compared with placebo. Based on these findings, valsartan became the first ARB to be approved by the US Food and Drug Administration for the treatment of New York Heart Association class II-IV HF in patients who are intolerant of ACEIs. This review provides a summary of the key Val-HeFT results and their implications in the treatment of CHF patients.
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PMID:The benefits of valsartan in the treatment of heart failure: results from Val-HeFT. 1505 67

Chronic heart failure affects between 1-5% of the population and rise steeply with age. Most patients with chronic heart failure should be routinely managed with a combination of 4 types of drugs: a diuretic, an angiotensin converting enzyme inhibitors (ACE-I), beta-blocker and usually digitalis. Diuretics are essential for symptomatic treatment when fluid overload is present, and should always be administrated in combination with ACE-I if possible. ACE-I improves survival and symptoms and reduces hospitalization in patients with moderate to severe ventricular systolic dysfunction, and in the absence of fluid retention should be given first. Angiotensin II receptor antagonist could be considered in patients who not tolerate ACE-I. beta-blocking agents are recommended for treatment of patients with stable, mild, moderate and severe heart failure unless there is a contraindication. Bisoprolol, metoprolol and carvedilol have been associated with reduction in total mortality, cardiovascular mortality and sudden death. Cardiac glycosides are indicated in atrial fibrillation and any degree of symptomatic heart failure in order slow ventricular rate. Indications for antiarrhythmic drug therapy include atrial fibrillation, non-sustained or sustained ventricular tachycardia. Oral anticoagulation reduces the risk of stroke in patients with atrial fibrillation, and there is a lack of evidence to support the use of antithrombotic therapy in patients in sinus rhythm.
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PMID:[Pharmacotherapy of chronic heart failure in clinical practice]. 1551 21

The introduction of Angiotensin II receptor blockers (ARB) in 1995 was another milestone in the pharmacological management of hypertension. Due to the manifold effects on several target organs Angiotensin II is one of the most important mediator in the pathogenesis of hypertension. The blockade of the Angiotensin II receptor type 1 is a crucial cornerstone in interrupting the pathophysiological pathways in hypertension. Furthermore ARB have an excellent tolerability comparable with placebo. In the last decade large placebo-controlled trials could prove the efficiency of ARB in terms of morbidity and mortality. Patients after acute myocardial infarction and patients with chronic heart failure benefit from treatment with ARB equally compared to treatment with ACE inhibitors. Combining ARB and ACE inhibitors in patient after myocardial infarction increases the rate of adverse events without improving survival. Increase of microalbuminuria and worsening of diabetic nephropathy is reduced by ARB in patients with diabetes type 2, but an advantage over ACE inhibitors could not be documented. Hypertensive patients with electrocardiographically left ventricular hypertrophy treated with ARB seem to have an additional benefit in terms of morbidity and mortality compared to treatment with beta-blockers. In the early treatment of stroke patients treated with ARB have a lower 12-mounth mortality than patients receiving placebo. In conclusion, Angiotensin II receptor blockers are due to their well proved efficiency, the cardio- and renoprotective qualities and the excellent tolerability profile a useful therapeutic option in the management of patients with hypertension.
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PMID:[Angiotensin II receptor blockers--evidence along the cardiovascular continuum]. 1588 24

Almost 5 million individuals in the United States are diagnosed with chronic heart failure (HF), and the prevalence is increasing. Angiotensin-converting enzyme (ACE) inhibitors and beta blockers, neurohormonal antagonists that block the renin-angiotensin system (RAS) and the sympathetic nervous system, respectively, have been shown in clinical trials to reduce morbidity and mortality in patients with HF, and these therapies are now integral components of standard HF treatment. Yet, morbidity and mortality rates in HF remain unacceptably high, and the limitations of current standard therapies are becoming increasingly apparent. About 10% of patients with HF are unable to tolerate ACE inhibitors, often because of cough. In addition, ACE inhibition may not completely block the RAS because angiotensin II, the main end product of the RAS, can be generated via non-ACE enzymatic pathways. Angiotensin II receptor blockers (ARBs) may exert more complete RAS blockade than ACE inhibitors by interfering with the binding of angiotensin II at the receptor level, regardless of the enzymatic pathway of production. They are also better tolerated than ACE inhibitors and have been shown to improve symptoms and function in clinical trials in patients with HF. These factors provide a strong rationale for the study of the clinical effects of ARBs in patients with HF.
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PMID:Rationale for the use of angiotensin II receptor blockers in patients with left ventricular dysfunction (part I of II). 1597 54

(1) Some angiotensin-converting-enzyme inhibitors (ACE inhibitors) reduce mortality in patients with heart failure (captopril, enalapril, ramipril and trandolapril), and in patients with recent myocardial infarction and heart failure or marked left ventricular dysfunction (captopril, ramipril and trandolapril). (2) Angiotensin II receptor antagonists, otherwise known as angiotensin receptor blockers, have haemodynamic effects similar to ACE inhibitors, but differ in their mechanism of action and certain adverse effects. (3) Five clinical trials have evaluated angiotensin II receptor antagonists (candesartan, losartan and valsartan) in terms of their effect on mortality and on the risk of clinical deterioration in patients with symptomatic heart failure, but without severe renal failure, hyperkalemia or hypotension. In these trials, candesartan and valsartan were used at much higher doses than those recommended for the treatment of arterial hypertension. (4) In patients with heart failure who were not taking an angiotensin II receptor antagonist or an ACE inhibitor at enrollment, no significant difference was found between losartan and captopril in terms of mortality or the risk of clinical deterioration. (5) In patients with heart failure who had stopped taking an ACE inhibitor because of adverse effects, candesartan had no effect on mortality as compared with placebo, but it did reduce the risk of clinical deterioration (3 fewer hospitalisations per year per 100 patients). However, candesartan was associated with adverse effects such as renal failure and hyperkalemia, especially in patients who had experienced these same adverse effects while taking an ACE inhibitor. (6) In patients with heart failure who were already taking an ACE inhibitor, adjunctive candesartan or valsartan treatment did not influence mortality in comparison to the addition of a placebo. Adding candesartan or valsartan reduced the risk of hospitalisation (between 1 and 3 fewer hospitalisations per year per 100 patients), but increased the risk of renal failure and hyperkalemia. (7) In patients with heart failure and incapacitating dyspnea despite ACE inhibitor + diuretic combination therapy, there are no trials comparing the addition of an angiotensin II receptor antagonist versus spironolactone. Adjunctive spironolactone therapy prevents 5 to 6 deaths per year per 100 patients in this setting. (8) In patients with heart failure who do not have markedly altered cardiac contractility, candesartan appears to have no clinical advantages over placebo. (9) In some of these trials, mortality was higher with angiotensin II receptor antagonist therapy than with placebo among patients who were already taking a betablocker. (10) Two trials have compared an angiotensin II receptor antagonist with an ACE inhibitor in patients with recent myocardial infarction who had heart failure or an altered left ventricular ejection fraction, but who did not have hypotension or severe renal failure. However, there are no placebo-controlled randomised trials assessing the effects of angiotensin II receptor antagonists on mortality. (11) In patients with recent myocardial infarction, these trials showed no difference in mortality between angiotensin II receptor antagonist treatment (losartan or valsartan) and captopril. They did not rule out the possibility that these angiotensin II receptor antagonists are moderately less effective than captopril. Adding valsartan to ongoing captopril therapy did not reduce mortality or morbidity as compared with placebo, but did increase the risk of adverse effects. (12) Overall, these trials confirm the advantage of angiotensin II receptor antagonists over ACE inhibitors with respect to some adverse effects (cough, skin rash, etc.). However, the two drug classes share certain serious adverse effects such as hyperkalemia, renal failure and hypotension. In one trial, angioedema was less frequent with angiotensin II receptor antagonist therapy (one less case per 500 patients).
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PMID:Angiotensin II receptor antagonists and heart failure: angiotensin-converting-enzyme inhibitors remain the first-line option. 1628 75

Clinical trials have shown that effective control of blood pressure reduces the risk of cardiovascular events in high-risk patients. For example, data from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study show significant reductions in the incidence of cardiac events, stroke and all-cause mortality in patients in whom blood pressure control was achieved compared with those in whom blood pressure remained uncontrolled. Although the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) demonstrated no significant difference in cardiovascular mortality and morbidity between patients receiving diuretics, calcium channel blockers or angiotensin-converting enzyme (ACE) inhibitors, this finding might have been confounded by differences in the blood pressure reductions achieved with the three treatments. Other studies have consistently shown that newer antihypertensive agents, such as ACE inhibitors and calcium channel blockers, reduce cardiovascular events to a similar, or possibly greater, extent as older therapies, such as diuretics and beta-blockers. In particular, ACE inhibitors appear to offer additional benefits beyond blood pressure reduction in terms of reducing cardiovascular events and producing renoprotective effects. Angiotensin II receptor blockers (ARBs) have been less extensively studied, but there is evidence already that they have heart failure, stroke and renoprotective benefits. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) is currently comparing the effects of the ARB telmisartan 80 mg and the ACE inhibitor ramipril 10 mg, alone and in combination, on cardiovascular events in high-risk patients.
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PMID:Hypertension treatment and implications of recent cardiovascular outcome trials. 1660 60

The renin-angiotensin-aldosterone system plays a key role in the regulation of fluid and electrolyte balance. Angiotensin II receptor blockers (ARBs) inhibit angiotensin II type 1 receptors and large clinical trials have shown that they are effective in many cardiovascular diseases including hypertension, heart failure, myocardial infarction and diabetic nephropathy. They lower blood pressure effectively, are very well tolerated and can be used as monotherapy or in combination with other drug classes for the treatment of hypertension. ARBs are particularly suitable for hypertensive patients with co-morbidities such as diabetes, microalbuminuria, proteinuria, left ventricular hypertrophy and heart failure. Unlike angiotensin-converting enzyme inhibitors, ARBs do not cause persistent dry cough. For patients in whom angiotensin-converting enzyme inhibitors are indicated but not tolerated, an ARB should be considered. Periodic monitoring of renal function and electrolytes is required in patients treated with an ARB.
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PMID:Therapeutic potential of angiotensin receptor blockers in hypertension. 1673 15

The number of hospitalizations for heart failure has continued to increase despite rapid and significant advances in cardiovascular care. The mortality rate is lower, but morbidity remains significant. In 2004, over 1 million people were hospitalized for heart failure. Conservative estimates indicate that the United States spends more than $33 billion annually, with hospital and nursing home costs consuming 75% of the total, home health care 10%, care providers 8%, and drugs and medical durables 8%. Angiotensin-converting enzyme inhibitor use confers a 16-20% reduction in mortality. beta-Blocker use also confers a significant reduction in mortality, as well as reduces hospitalizations. Angiotensin II receptor blockers also reduce mortality and morbidity. Appropriate use of drugs can reduce other costs associated with heart failure. During the past 20 years, many trials in patients with heart failure have been conducted. Those that have demonstrated reductions in morbidity and mortality were reviewed in order to identify the important implications for sound clinical care of patients with heart failure. Managed care practitioners and pharmacists who take the time to revisit pertinent studies will understand how each incremental knowledge enhancement builds on previous data. They will also know which agents are preferred based on well-conducted clinical trials, as well as the target doses at which these agents should be used.
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PMID:New studies influencing treatment of heart failure: 2006 update. 1738 69

Angiotensin II receptor blockers (ARBs) are widely used in patients with hypertension, heart failure, diabetic nephropathy, and other conditions. Over-stimulation of AT2 receptor as a result of AT1 blockade may contribute to the beneficial effects of ARBs through vasodilation and inhibition of cardiac and vascular hypertrophy and fibrosis. Some experimental studies, however, suggested that AT, receptor overstimulation, in addition to beneficial effects, might trigger inhibition of angiogenesis and apoptosis. In a review, some authors suggested that ARBs may increase the risk of myocardial infarction. This position triggered a hot scientific debate and further analyses of existing data. We completed a meta-analysis of randomized clinical trials comparing ARBs with either placebo or active drugs different from ARBs. ARBs were not associated with an excess risk of myocardial infarction (odds ratio 1.03 in a random-effect model and 1.02 in a fixed-effect model). Cardiovascular mortality did not differ between ARBs and drugs different from ARBs (odds ratio 1.00 in a random-effect model and 0.99 in a fixed-effect model) and it was slightly lesser with ARBs than with placebo (odds ratio 0.91; 95% confidence interval 0.83-0.99; p = 0.042) in a prespecified subgroup analysis. Other meta-analyses confirmed these data. In conclusion, evidence from randomized trials does not support the hypothesis that AT2 receptor over-stimulation produces harmful clinical effects. Current indications and contraindications to the use of ARBs in patients with hypertension, heart failure, and diabetic nephropathy should be maintained and probably extended to the entire class of these drugs.
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PMID:[Antihypertensive therapy and cardiovascular prevention. The role of angiotensin II receptor blockers]. 1769

Angiotensin II receptor blockade (ARB) increases vasorelaxation in heart failure by enhancing endothelial nitric oxide (NO). To determine the effects of valsartan on NO-mediated peripheral vascular function after myocardial infarction (MI), we treated adult male Sprague-Dawley rats immediately after MI with valsartan for 3 weeks (sham, n = 10; MI, n = 11) and 6 weeks (sham, n = 6; MI, n = 8). At both time points, valsartan lowered (P < 0.05) left ventricular (LV) systolic pressure (103 +/- 4 and 107 +/- 4 vs. 93 +/- 3 and 85 +/- 4 mm Hg, respectively) and LV end-diastolic pressure (25 +/- 1 and 25 +/- 2 to 13 +/- 2 and 18 +/- 3 mm Hg, respectively). Valsartan lowered (P < 0.05) LV dP/dt only at 6 weeks (4676 +/- 168 and 4503 +/- 232 vs. 4539 +/- 281 and 3372 +/- 417 mm Hg/sec); valsartan shortened (P < 0.05) the time constant of LV relaxation or tau only at 3 weeks (24.2 +/- 1.8 and 26.5 +/- 2.3 vs. 20.1 +/- 0.7 and 23.8 +/- 1.4 msec). At 6 weeks, the vasorelaxation response to acetycholine in aortic rings was decreased (P < 0.05) with MI and improved at acetycholine doses (10, 10, and 10; P < 0.06) with valsartan. Endothelial nitric oxide synthase (eNOS) protein was undetectable in aortic tissue from valsartan treated rats or from aortic tissue incubated with valsartan (2.5, 25, and 50 mg/mL). These data suggest that valsartan improves cardiac function after MI by modulating LV remodeling, decreasing LV end-diastolic pressure, and enhancing both LV diastolic and endothelial function. These effects are mediated, in part, by NO but upregulation of eNOS may not be required for improved systemic endothelial function in heart failure.
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PMID:Valsartan therapy in heart failure after myocardial infarction: the role of endothelial dependent vasorelaxation. 1809 89


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