Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based upon the results of the RALES trial and accumulating evidence about the role of aldosterone and aldosterone receptor antagonism in various disease states, the authors anticipate that aldosterone receptor antagonists will become standard therapy, along with ACE inhibitors and beta-adrenergic receptor blocking agents, in patients with heart failure that is caused by systolic left ventricular dysfunction. Furthermore, the prospect of the use of these agents in other disease states that have implicated an activated rennin-angiotensin-aldosterone cascade, such as diastolic dysfunction, aging, and atherosclerosis, remains to be tested. Until further data from well-designed, prospective, randomized trials are available, the use of aldosterone receptor antagonists should be restricted to patients with severe or progressive heart failure caused by systolic left ventricular dysfunction in whom serum creatinine level is < or = 2.0 mg/dL and serum potassium levels are < 5.0 meq/L at baseline.
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PMID:Aldosterone as a target in congestive heart failure. 1269 33

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

Aldosterone is present and active all along the cardiovascular continuum. Excessive tissue production occurs in cardiovascular diseases including myocardial infarction (MI) and heart failure, resulting in a multitude of adverse effects in the cardiovascular system necessitating pharmacologic blockade of this neurohormone. Both human and animal studies have consistently proven the beneficial effects of antialdosteronics in the improvement of: 1) endothelial function, 2) modulation of inflammatory mechanisms between blood and the vascular wall and 3) reduction of tissue proliferation and cardiovascular remodeling leading to different severities of cardiovascular damage. These basic mechanisms of anti-aldosterone therapy strongly support the promising data observed in major clinical trials with aldosterone blockers in cardiovascular diseases, specially in heart failure patients. Whereas aldosterone receptor blockers were initially viewed as potassium-sparing diuretics there has been a clear change of concept in the past 10 years, mainly following the positive results of RALES with spironolactone in chronic heart failure, followed by EPHESUS using eplerenone in patients with systolic dysfunction post MI. The significant positive results in both studies were a clear support for the inclusion of this pharmacologic intervention as first line treatment in most international guidelines for the management of heart failure. More recent and ongoing studies are exploring the usefulness of this type of intervention in preventing vascular and myocardial hypertrophy and remodeling in refractory hypertensive and some hyperfibrotic syndromes. There are also provocative studies investigating in the possibility of inhibiting atherosclerosis. More recently, some studies are suggesting the benefit of aldosterone blockade in sleep apnea. In addition, two large multicentric trials, TOPCAT and EMPHASIS are analyzing the potential use of antialdosteronics in patients with cardiac insufficiency and preserved systolic function and the possibility of extending their indication in systolic heart failure to Phase II respectively. New compounds, blocking the synthesis of aldosterone instead of blocking its receptor are being developed, and initial Phase 2 studies are positive. All of the above results are very interesting, show an optimistic future and are consolidating and enlarging the spectrum of aldosterone blockade in cardiovascular disorders every day.
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PMID:Aldosterone inhibition and cardiovascular protection: more important than it once appeared. 2067 26