Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Clinical value of pharmacologic blockade of renin angiotensin aldosterone system for deceleration of cardiovascular continuum is strongly proved. Up to 20% of population is intolerant to ACE inhibitors. There are no strong evidences that ACE inhibitors differ from angiotensin receptors blockers in influence on main cardiovascular outcomes. In placebo controlled randomized multicentre trial TRANSCEND clinical efficacy, safety and tolerability of telmisartan was studied in elderly patients with high cardiovascular risk who were intolerant to ACE inhibitors. Telmisartan based therapy was associated with decrease of secondary end point (composite of cardiovascular death, myocardial infarction, or stroke) by 13% in comparison with placebo (p=0.048). There were significantly less hospitalizations due to cardiovascular causes in telmisartan group than in placebo group. Risks of new diabetes mellitus, renal dysfunction and serious adverse events were similar in both groups. Combined results of TRANSCEND and PRoFESS trials have demonstrated significant advantage of active telmisartan based therapy concerning the primary outcome of composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure ( 7%, p=0.026).
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PMID:[Modern tendencies in the treatment of patients with high risk of development of cardiovascular complications and intolerance to angiotensin converting enzyme inhibitors: value of results of TRANSCEND trial for clinical practice]. 1946 25

Angiotensin-converting enzyme (ACE) inhibitors are useful drugs for preventing cardiovascular disease and death in patients at risk. However, a significant proportion of patients experience side effects, mainly cough or less frequently angioedema, when treated with ACE inhibitors. Angiotensin receptor blockers (ARBs) are also useful drugs for treatment of hypertension, diabetic nephropathy and patients with left ventricular dysfunction or cardiac failure who are intolerant to ACE inhibitors. The Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) study examined the effect of a long-acting ARB, telmisartan, on cardiovascular events in a group of patients at high-risk for cardiovascular disease who were intolerant to ACE inhibitors. Five thousand nine hundred twenty-six patients with known intolerance to ACE inhibitors were randomized to telmisartan or placebo added to current treatments. The primary composite endpoint, a sum of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and hospitalization due to heart failure was nonsignificantly reduced in telmisartan-treated patients with respect to placebo (15.7 vs. 17%; relative risk reduction 8%). The key secondary endpoint (the primary endpoint excluding heart failure hospitalization) was reduced in telmisartan-treated patients by 13% (13 vs. 14.8%; P = 0.046). In conclusion, telmisartan reduces cardiovascular events in high-risk patients with the exception of heart failure hospitalization and can be considered as the first-line therapy in those intolerant to ACE inhibitors.
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PMID:Main results and clinical interpretations from the TRANSCEND study. 1949 18

In patients with arterial hypertension and/or high cardiovascular risk, including patients with diabetes, chronic ischemic heart disease and kidney disease, the risk of heart failure decreases with blood pressure reduction and the use of drugs that inhibit the renin-angiotensin system (RAS) [angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)]. The heart failure incidence seen in ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) is in line with this observation. In ONTARGET, telmisartan and ramipril were equally effective in heart failure prevention and with the same blood pressure reduction. The low event rate, including the low incidence of heart failure in TRANSCEND with the greater use of diuretics in the placebo arm, may help to explain the absence of significant differences between telmisartan and placebo.
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PMID:The question of heart failure in ONTARGET and TRANSCEND: implications for clinical practice. 1949 21

The renin-angiotensin system (RAS) plays an important role in the pathogenesis of cardiovascular disease. One of the effects of the activated RAS is target-organ damage, in part due to their effects on causing hypertension. Blocking angiotensin-converting enzyme (ACE) with inhibitors has been shown to attenuate the pathological effects of the RAS. Clinical trials have shown that ACE inhibition improves outcomes in the prevention of acute myocardial infarction, lowering the morbidity and mortality in congestive heart failure, and attenuates renal dysfunction. There is recent evidence to show that angiotensin receptor blockers (ARBs) have similar efficacy to ACE inhibitors in reducing cardiovascular outcomes. The wealth of information obtained regarding the beneficial effects of RAS inhibition on clinical outcome has been focused on monotherapy with either ARB or ACE inhibition. Evidence from some trials suggests that better overall inhibition of RAS by dual therapy may improve clinical outcomes. Combination therapy has been shown to be beneficial in patients with congestive heart failure or renal disease. The Valsartan in Acute Myocardial Infarction Trial (VALIANT) trial showed equal benefit of either ARB or ACE inhibition with reduction in primary end points in postmyocardial infarction patients, but there was no further benefit from dual therapy in reducing outcomes. In the recent ONTARGET study, there was further evidence that ARBs are equal to ACE inhibitors in reducing cardiovascular events. In Ongoing Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events (ONTARGET), combined RAS blockade did not have any added benefit but resulted in increased risk of adverse outcomes. In the Candesartan in Heart Failure (CHARM) and the Valsartan Heart Failure Trial (Val-HeFT) trials of patients with severe heart failure, the addition of an ARB to an ACE inhibitor reduced cardiac mortality and lowered hospital admissions. Whether or not dual therapy is beneficial in patients with diabetic renal failure should be clarified by future studies. Overall, patients receiving dual therapy, if clinically justified, should be monitored closely for potential adverse effects.
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PMID:Blocking the renin-angiotensin system: dual- versus mono-therapy. 1950 82

The benefits of blood pressure control on the risks of major cardiovascular events are well established. In clinical trials conducted in patients with mild-to-moderate hypertension, the angiotensin II receptor blocker (ARB) telmisartan has been shown to provide reduction of blood pressure throughout the 24-h dosing interval. Clinical trials have also demonstrated that ARBs are effective agents in reducing the risk of cardiovascular mortality, stroke, heart failure and new-onset atrial fibrillation. Recently, the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study established that telmisartan reduces morbidity and mortality in a broad cross-section of patients at high risk for heart and vascular events, to an extent similar to that of the angiotensin-converting enzyme inhibitor ramipril. In addition, ONTARGET demonstrated that telmisartan is somewhat better tolerated than ramipril. Attributes such as effective blood pressure lowering, tolerability and convincing outcomes data mean that ARBs satisfy the requirements for first-line antihypertensive agents.
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PMID:Achieving blood pressure goals: should angiotensin II receptor blockers become first-line treatment in hypertension? 1958 55

Hypertension is a comorbidity of Type 2 diabetes, and blood pressure lowering has been shown to reduce cardiovascular (CV) and renal disease progression in this population. Angiotensin-converting enzyme (ACE)-inhibitors have demonstrated reduction in CV mortality and myocardial infarction, stroke, and heart failure in patients with diabetes. Evidence suggests that angiotensin receptor blockers (ARBs) have similar CV protective effects, particularly in patients post-myocardial infarction and in those with heart failure, and their renoprotective effects have reduced proteinuria in patients with or without diabetes. In addition, ARBs have been shown to reduce diabetic nephropathy and complications related to nephropathy. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint trial (ONTARGET) is the first trial to demonstrate that the ARB, telmisartan, is as effective as the ACE-inhibitor, ramipril, in CV protection in a high-risk, ACE-tolerant population. Whether all ARBs are equally cardioprotective is uncertain. Data indicate that the beneficial effects of telmisartan may be drug specific rather than constitute a 'class effect.'
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PMID:Role of angiotensin receptor blockers in diabetes: implications of recent clinical trials. 1990 19

Angiotensin-receptor blockers (ARBs) offer superior tolerability to angiotensin-converting enzyme inhibitors, and are increasingly used in patient management. ARBs vary in their pharmacological profiles, which results in efficacy differences. Therefore, deciding between ARBs should be evidence-based and related to the specific requirements of the individual patient. For patients with hypertension but at low additional risk, an ARB that provides sustained, powerful 24-h reductions in blood pressure is suitable. For patients at very high additional risk (with heart failure), an ARB with demonstrated efficacy in this patient population is the preferred option. For patients at increased risk, telmisartan should be the ARB of choice based on the results from the Ongoing Telmisartan Alone and in Combination with Ramipril Global End Point Trial (ONTARGET), which demonstrated for the first time that an ARB has equivalent protection to the reference angiotensin-converting enzyme inhibitor in a broad cross-section of at-risk patients but a better side-effect profile.
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PMID:Choosing an angiotensin-receptor blocker: blood pressure lowering, cardiovascular protection or both? 2001 92

The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of a variety of clinical conditions, including atherosclerosis, hypertension, left ventricular hypertrophy, myocardial infarction, and heart failure. Inhibition of the RAAS with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ARBs) has been shown to be effective in lowering blood pressure and reducing cardiovascular mortality and morbidity in various at-risk patient populations. A number of studies have shown that these 2 classes are effective in reducing the rate of renal disease progression in patients with diabetic nephropathy, although more long-term vascular outcome studies are needed in patients with chronic kidney disease. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) was the first study to show comparable reno- and cardioprotective effects between an ARB (telmisartan) and ramipril in a broad section of at-risk patients, on top of usual standard care. However, telmisartan showed better tolerability than ramipril in ONTARGET, with less cough and angioedema. This difference was obtained despite patients having been selected for tolerability to both drugs at study entry.
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PMID:Renin-angiotensin system blockade and cardiovascular and renal protection. 2045 6

ATP-binding cassette (ABC)-transporters, such as P-glycoprotein (P-gp/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs) and breast cancer resistance protein (BCRP/ABCG2) transport numerous drugs thus regulating their absorption, distribution and excretion. Angiotensin receptor type 1 blockers (ARBs), used to treat hypertension and heart failure, are commonly administered in combination therapy. However, their interaction potential is not well studied and their effect on ABC-transporters remains elusive. The study therefore aimed to elucidate the effect of various ARBs (telmisartan, candesartan, candesartan-cilexetil, irbesartan, losartan, olmesartan, olmesartan-medoxomil, eprosartan) on ABC-transporter activity in vitro. P-gp inhibition was assessed by calcein assay, BCRP inhibition by pheophorbide A efflux assay, and MRP2 inhibition by a MRP2 PREDIVEZ Kit. Induction of P-gp, BCRP and MRP2 was assessed by real time reverse transcriptase polymerase chain reaction and for P-gp also in a functional assay. Telmisartan was identified as one of the most potent inhibitors of P-gp currently known (IC(50)=0.38+/-0.2 microM for murine P-gp) and it also inhibited human BCRP (IC(50)=16.9+/-8.1 microM) and human MRP2 (IC(50)=25.4+/-0.6 microM). Moreover, the prodrug candesartan-cilexetil, but not candesartan itself, significantly inhibited P-gp and BCRP activity. None of the compounds tested induced mRNA transcription of P-gp or BCRP but eprosartan and olmesartan induced MRP2 mRNA expression. In conclusion, telmisartan substantially differed from other ARBs with respect to its potential to inhibit ABC-transporters relevant for drug pharmacokinetics and tissue defense. These findings may explain the known interaction of telmisartan with digoxin and suggest that it may modulate the bioavailability of drugs whose absorption is restricted by P-gp and possibly also by BCRP or MRP2.
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PMID:Interaction of angiotensin receptor type 1 blockers with ATP-binding cassette transporters. 2022 53

Multiple trials over the past several years have examined indications for angiotensin receptor blockers (ARBs) in the treatment of left ventricular (LV) dysfunction, both acutely after myocardial infarction and in chronic heart failure (CHF). However, the effects of telmisartan, an ARB in rats with CHF after experimental autoimmune myocarditis (EAM) have not yet been analyzed. CHF was elicited in Lewis rats by immunization with cardiac myosin, and 28 days after immunization, the surviving Lewis rats were divided into two groups and treated with either telmisartan (10 mg kg(-1) day(-1)) or vehicle. After 4 weeks of treatment, we analyzed the effects of telmisartan on cardiac function, proinflammatory cytokines and cardiac remodeling in EAM rats. Myocardial functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by telmisartan treatment in rats with CHF compared with those of vehicle-treated rats with CHF. Telmisartan significantly reduced levels of cardiac fibrosis, hypertrophy and its marker molecules (LV mRNA expressions of transforming growth factor beta 1, collagen I and III, and atrial natriuretic peptide), and peroxisome proliferator-activated receptor--gamma protein expression compared with those of vehicle-treated rats. CHF-induced increases in myocardial mRNA expressions of proinflammatory cytokines, (interleukin (IL)-6, IL-1beta), monocyte chemoattractant protein-1 and matrix metalloproteinases (MMP-2 and -9) were also suppressed by the treatment with telmisartan. Moreover, the plasma level of angiotensin-II was significantly elevated in telmisartan-treated rats. Our results indicate that telmisartan treatment significantly improved LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM.
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PMID:Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy. 2053 15


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